Department of Pediatrics - PDF Free Download (2023)

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1 Department Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 1

2 A MESSAGE FROM OUR LEADERSHIP We are pleased to share with you some of the milestones achieved by the Department, in collaboration with Rady Children s Hospital and the Medical Practice Foundation. We celebrate the meaningful contributions of our physicians, physician-scientists and scientists in this report. For years, the Department at UC San Diego (UCSD), Rady Children s Hospital and the Medical Group in the Medical Practice Foundation have shared a commitment to the health and well-being of children in San Diego County and beyond. The collaboration between these entities unified patient care, research, education, community service programs, and advocacy in the region. It has led to national recognition for world-class pediatric care and research and the potential to change the course of pediatric medicine. As an example for this achievement, we now care for about 85% of the children in San Diego County and 50% of Imperial and Riverside Counties, thus amounting to about 900,000 children seeking medical and surgical advice at Rady Children s Hospital. Another illustration is the increase in research revenues from about $25 million in to about $61 million dollars in each of the past 2 years. With the opening of an additional pavilion at Rady Children s, a few years ago, this Hospital has become the largest children s hospital in California and the eighth largest in the country. In the last consecutive few years, the Hospital was ranked in all 10 pediatric specialties surveyed by U.S. News & World Report. Those rankings place the Hospitals among the nation s elite children s hospitals, and are even more remarkable considering the relative youth of Rady Children s, compared to other children s hospitals, which have built their reputations over many more decades. Sincerely, GABRIEL HADDAD, MD Distinguished Professor and Neurosciences Chairman, Department University of California, San Diego Physician-In-Chief and Chief Scientific Officer Rady Children s Hospital-San Diego DONALD KEARNS, MD President and CEO Rady Children s Hospital-San Diego HERBERT C. KIMMONS, MD President Rady Children s Specialist of San Diego Executive Director, Medical Practice Foundation Dean, Children s Clinical Services University of California, San Diego - ACKNOWLEDGEMENTS - Thank you to these Department staff members for their contributions, who made this Biennial Report possible: Mercedes Alcoser Jodi Bengel Melanie Marshall And appreciation is given to the Divisions for their contributions and assistance. 2 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 3

3 TABLE OF CONTENTS Introduction...6 RCHSD Affiliations...10 RCHSD By the Numbers...11 Academic General Pediatrics, Child Development & Community Health...14 Allergy, Immunology & Rheumatology...30 Critical Care & Anesthesia...44 Dermatology...52 Dysmorphology & Teratology...64 Emergency Medicine...74 Endocrinology...86 Gastroenterology, Hepatology & Nutrition Genetics TABLE OF CONTENTS Genome Information Sciences Heart Institute(Cardiology and Cardiothoracic Surgery) Hematology/Oncology Hospital Medicine Host-Microbe Systems & Therapeutics Infectious Diseases Neonatology Nephrology Neurology Residency Program Respiratory Medicine Vulnerable Children UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 5

4 INTRODUCTION In the last several years, considerable progress has been made in strengthening and expanding the mission, services, and resources of the Department. These successes have created a welcomed ripple effect which strengthens and furthers the clinical, academic and scientific achievements of Rady Children s Hospital and the University of California, San Diego. The Department is critically dependent on both institutions for resources, therefore fostering, nurturing and growing this relationship is essential to everyone s success. In this Biennial Report, many of the major accomplishments of our divisions and faculty are highlighted. We hope you enjoy this issue, and we welcome your feedback and questions. ACADEMIC GENERAL PEDIATRICS, CHILD DEVELOPMENT & COMMUNITY HEALTH The Division has vibrant academic-research partnerships locally, across the U.S., and in Mexico and Chile. The Child Development-Behavioral Pedediatrics fellowship program was awarded the highly competitive HRSA, Maternal Child Health Bureau grant for Leadership in Education in Developmental-Behavioral Pediatrics (07/01/ /30/2018). The Center for Community Health has funding from the National Institutes of Health, American Heart Association, Centers for Disease Control and Prevention, The San Diego County Health and Human Services Agency Centers for Disease Control and Prevention, The San Diego County Health and Human Services Agency, the Network for a Healthy California Foundation and other foundations, totaling $2,203,968. A number of physicians in this division were named "San Diego Top Doctors. " ALLERGY, IMMUNOLOGY & RHEUMATOLOGY The Division maintains an internationally recognized research program in the areas of translational and clinical research in autoinflammatory disorders, genetics of rare inherited diseases, Kawasaki disease, food allergy, eosinophilic esophagitis, and basic research in T cell immunology, and is currently building clinical research programs in pediatric rheumatology, severe asthma, and immunodeficiency. Dr. S. Aceves was elected to the American Society of Clinical Investigation in Dr. Hoffman has been a member since Dr. L. Broderick obtained a K08 last year. Dr. R. Sheets received the Hospital Teaching Award as well as the Teaching Award from the Residents. CRITICAL CARE & ANESTHESIA This division is consistently ranked in the top few programs for observed:predicted mortality rates. DERMATOLOGY The division is one of the largest pediatric dermatology units in the United States, and is a highly respected center with a national and international reputation for clinical, research and educational excellence. The academic years were very successful, with significant contributions to the fields of dermatology and pediatrics in research, leadership, and advocacy, and expansion of the clinical services. The Division exceeded 20,000 patient visits and over 1,500 surgical, laser and phototherapy procedures per year, with services in satellite clinics throughout San Diego County, including Oceanside, Murrieta, Encinitas and Escondido. The research program broadened its research work in inflammatory skin disease. DYSMORPHOLOGY AND TERATOLOGY The division employed over 70 clinical and research staff, had $27,760,070 in total funding, and published 56 manuscripts, 6 book chapters and 1 book. The Division remains at the forefront both nationally and internationally in the field of Fetal Alcohol Spectrum Disorders (FASD). Advances include the award of a 4 year grant from the CDC to train pediatricians and nurses in the prevention of alcoholexposed pregnancies; the development of a telemedicine program whereby a long-distance evaluation of a child for FASD can be conducted; the launching of nurse conducted FASD screenings; and creating the SoCal NOFAS website and a local bilingual support group for families affected by FASD. Dr. Tina Chambers received the Rady Children s Hospital Excellence in Research Award in EMERGENCY MEDICINE The Emergency Medicine Division is the busiest pediatric emergency Room on the West Coast, seeing over 90,000 patients in 2015, and is the 5th busiest in the U.S.! For the past year, the LWBS has been below 0.5. ENDOCRINOLOGY The Division was recognized among the top 30 programs in Pediatric Endocrinology in the U.S. News & World Report ranked number 16 in 2013 and 12 in The Diabetes Center at RCHSD received the American Diabetes Association Recognition Award for meeting the standards of education in diabetes self-management. GASTROENTEROLOGY, HEPATOLOGY & NUTRITION The Fatty Liver Clinic was the first of its kind in the country to care for children and adolescents with fatty liver disorders. The stateof-the-art care is complemented by an active research program on obesity and fatty liver disease. With more than $8 million in research funding relating to gastroenterology, hepatology, and nutrtion, the Division is a growing national leader in generation of new knowledge relating to the field being at the forefront of scientific research in areas such as obesity and its metabolic complications, chronic liver diseases including steatohepatitis, as well as intestinal biology and immunology. Dr. Lars Bode is the president-elect of the International Society for Research in Human Milk and Lactation Editorial Board Member - Advances in Nutrition. Dr. Mousa was named a Best Doctor in America and America s Top Physicians. GENETICS This Division has been remarkably successful in the past few years: The Division holds more than $5 million in grants and has published over 70 original articles and chapters within the last 2 years. published over 70 original articles and chapters within the last 2 yrs Dr. T. Friedmann got the Japan Prize in Dr. Al La Spada was inducted into the American Association of Physicians (AAP) in Dr. T. Rana got an Avant-Garde Award from the NIH in He also was elected fellow of the American Association for the Advancement of Science: GENOME INFORMATION SCIENCES The Division has grown also in the past few years. This Division has over $18 million in research funding. Dr. K. Frazer laboratory is involved in the NextGen Program of the National Human Genome Research Institute (NHGRI) and the Heart, Lung, and Blood Institute (NHLBI), which is aimed at generating and utilizing ipsc to investigate the biological mechanisms underlying disease association with genetic variants. Dr. Frazer s laboratory has specifically been funded to link cardiac molecular phenotypes to genotypes through the generation of ipsc-derived cardiomyocytes from 222 individuals in the CARDiPS collection. HEART INSTITUTE/CARDIOLOGY This division has grown immensely in the past few years, with two new programs starting Transplant (UNOS certification) 6 transplants were done in 2015 with 100% survival; 1 artificial heart. A major unit housing CVICU just been added with 12 beds. There have been 8 new faculty recruitments since 2014, bringing the total of Division faulty to 20. Awarded 3-star (highest) designation by Society of Thoracic Surgeons. Only 10 of 117 heart programs in nation have received this rating due to mortality rate being 1 point below average. The cardiac catheterization program has continued to increase reaching a total of more than 600 annually, making this program one of the largest program in the country. HEMATOLOGY/ONCOLOGY Division is part of a National Cancer Institute designated Comprehensive Cancer Center. Alliance with St. Jude Children s Research Hospital which focuses on the development of clinical, translational, and basic research in the area of childhood cancer. Currently, 12 joint clinical trials are available to the children of San Diego. Also, joint efforts in International Outreach have led to the creation of successful Pedatric Oncology Programs in Tijuana, Mexico and La Paz, Mexico. Dr. Bill Roberts was given the Rady Children s Hospital Annual Excellence in Clinical Care Award in 2015 Dr. D. Durden was appointed on the Editorial Board, Molecular Cancer Research (MCR)(AACR), 2015 Dr. J. Crawford was given the 2015 Senior Faculty Teaching Award from the Department of Neurosciences HOSPITAL MEDICINE The Division has seen expansion, and strong clinical and scholarship activities in the past few years. The Division began in 1978 by Dr. Irvin Buzz Kaufman, and is considered the oldest pediatric program in the nation. The Division developed one of the first 3 PHM Fellowship training programs in the country. Received superior scores in U.S. News and World Report for success with asthma inpatients and management of asthma patients. Dr. E. Fisher was named one of the Best Doctors in America, 2014, and listed in San Diego Magazine Top Doctors 2014, UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 7

5 HOST-MICROBE SYSTEMS & THERAPEUTICS Headquarters of the NIH/NICHD Sponsored Research Program in Developmental Pharmacology (RPDP), NIH/NIAID Funded Program in the Systems Biology of Antimicrobial Resistance, UCSD campus-wide Center for Microbiome Innovation (CMI). The Division has a robust Pharmacometrics Unit, recognized internationally for its leadership in pharmacokinetic and pharmacodynamic modeling, including sparse data collection techniques and population analysis methodologies that enable appropriate dosing in pediatric subpopulations. The Pediatric Pharmacology Laboratory (PPL) provides many core services for the NIAID/NIH International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) pharmacology program. Rob Knight: Co-founded the Earth Microbiome Project and the American Gut Project, both of which are primarily run from his laboratory at UCSD. Received the Vilcek Prize for Creative Promise in Biomedical Science and Thomson Reuters Highly Cited Researcher. Named in Science Watch and as "Hottest Scientific Researchers and Research." INFECTIOUS DISEASES This Division covers all the clinical activities in Infectious Disease at Rady, and has major research activities that span from basic research to population health, with faculty including Drs. Bradley, Spector and Sawyer. Dr. Bradley was the co-lead of the CDC/IDSA/PIDS National Guidelines Writing Group for the Diagnosis, Treatment and Prevention of Influenza and the Chair, PIDS/IDSA Guidelines Writing Committee for Pediatric Community Acquired Pneumonia. Dr. Sawyer was Member, FDA Vaccines and Related Biological Products Advisory Committee. Dr. Spector was on the Pediatric Antiretroviral Working Group of the World Health Organization (WHO) and a Panelist member, Perinatal HIV guidelines, Department of Health & Human Services. NEONATOLOGY This Division has grown tremendously and now has an "amalgamated division regarding teaching and research between Rady and UCSD NICUs. A number of faculty have been recruited to both units and a number of physician-scientists have been recruited to this Division. A number of faculty now rotate through both units and there is better collaboration now at all levels between faculty in main NICUs and region alone. Regionally, Neonatology has 208 NICU beds total. The Division has been ranked in the top 20 nationally by U.S. News & World Reports. Neonatology has also established a Neuro-NICU program. NEPHROLOGY Consistently recognized in U.S. News and World Report as one of the top Pediatric Nephrology programs in the US. Drs. Mak and Benador are an integral part of a longitudinal cohort of children with chronic kidney disease (CKiD) which has been continuously funded by the NIH for more than 10 years. Dr. Mak serves on the steering committee and Dr. Benador is the center PI of the CKiD study. Dr. E. Ingulli won the Teaching Attending of the Year, UCSD Residents. Dr. R. Mak has been on the Editorial Board of Nature Reviews Nephrology, 2009-present and Co-chair, Kidney Disease Progression Committee, NIH. Dr. E. Perens received the ASPN Presentation Award, PAS Annual Meeting, Vancouver, Canada, NEUROLOGY This Division has grown significantly and Jeff Neul was recruited from Baylor to head the Division. There are a number of clinical trials in neuro-oncology in collaboration with St. Jude Children s Hospital, the Pacific Pediatric Neuro-Oncology Consortium, and the Children s Oncology Group. Dr. John Crawford got the Junior Faculty Teaching Award Department of Neurosciences, University of California, San Diego, 2013 and was the Leonard Tow Humanism Award in Medicine Nominee, Dr. J. Gleeson was inducted into the Association of American Physicians as well as to the Institute of Medicine, National Academy of Sciences. Dr. Jeffrey Neul, MD, PhD is a standing member of the NIH, Neurological Sciences Training (NST- 1) Study Section, and the Molecular Neurogenetics Study Section. Dr. Doris Trauner, MD was elected to AOA Medical Honor Society, VCU/MCV School of Medicine, June 2013 and to the top 1% doctors in America, US News and World Report, PEDIATRIC RESIDENCY PROGRAM The goal of the Pediatric Residency Program at the UC San Diego/Rady Children s Hospital San Diego (RCHSD) is to train pediatricians to be well versed in all aspects of caring for sick and well children by integrating the art and science of pediatric medicine. The Program attracts medical students from major medical schools across the country and trains residents for careers in primary care and pediatric subspecialties. Located in the seventh largest city in the U.S. and on the border with Mexico, the program offers unique experiences in clinical and community pediatrics including exposure to border health and diverse populations including those from immigrant, inner-city, rural, and military communities. RESPIRATORY MEDICINE The Division has maintained a national ranking in Pulmonology in the U.S. News and World Report survey of children s hospitals since Two fellows have received prestigious Pediatrics Scientist Development Program (PSDP) Awards. Paul Quinton, PhD received the 2015 Distinguished Achievement Award, American Thoracic Society. There are several Best Doctors in America and Top Doctors: Gabriel Haddad, James Hagood, Daniel Lesser, Meerana Lim, and Julie Ryu. VULNERABLE CHILDREN The Chadwick Center s expertise in treating abuse-related trauma has led to collaborations with the National Child Traumatic Stress Network and the expansion of treatment to work with child and adolescent victims of other forms of violence (such as school shootings), natural disasters (wild fire victims), auto accidents and children undergoing painful medical procedures. The Center provides education to over 22,000 professionals from the US and 30 countries worldwide. The Center serves 9,400 children and families annually. 8 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 9

6 RCHSD AFFILIATIONS RCHSD BY THE NUMBERS RCHSD has developed formal affiliations with every hospital and medical group in the region. These partnerships include faculty joint ventures, specialty physician coverage, transfer agreements, & community health affiliations. performed 412 heart surgeries provided care to 214,216 children 18,782 inpatient admissions 84,918 emergency care visits & 54,149 urgent care visits cared for 275 newly diagnosed cancer patients, attended to 17,482 outpatient visits 230,383 outpatient visits Performed 19,982 general surgeries provided care to 709 trauma patients 10 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 11

7 RCHSD provides the majority of acute and specialty care for the children of San Diego County County Age Group RCHSD Pediatric Market Share San Diego County % South Riverside County** % Imperial County** % **RCHSD is a major out-of-region referral recipient Includes Temecula, Murrieta, Lake Elsinore Menifee & Wildomar 140, , , , ,000 90,000 80,000 70,000 60,000 50,000 40,000 30,000 20,000 EMERGENCY SERVICES VOLUME EMERGENCY CARE CENTER URGENT CARE CENTERS Source: Office of Statewide Health Planning and Development Hospital Discharge Data 10, INSURANCE PROVIDER BREAKDOWN Self-Pay & Charity Care 1.60% Out-of-State Medicaid 1.6% Medicare 0.50% 22,000 21,500 21,000 20,500 20,000 19,500 19,000 18,500 18,000 17,500 17,000 18,516 18,546 SURGICAL VOLUME ,229 19,017 18,984 19,914 21,419 21,132 20,927 20,454 20,668 20,679 20, ,982 ACUTE CARE HOSPITAL PATIENT DAYS COMMERICAL/ MANAGED CARE 36.10% MEDI-CAL 48% 100,000 90,000 80,000 70,000 60,000 57,384 57,261 59,585 62,238 64,430 68,848 68,337 67,780 70,895 76,815 75,332 85,654 89,394 91,640 50,000 40,000 30,000 20,000 10, UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 13

8 Academic General Pediatrics, Child Development & Community Health 14 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 15

9 INTRODUCTION FACULTY The Division of Academic General Pediatrics, Child Development & Community Health, led by Dr. Sheila Gahagan, focuses on clinical care and medical education in General Pediatrics, Adolescent Medicine, and Developmental-Behavioral Pediatrics. The Division has several robust research programs and provides considerable health promotion in the community. Dr. Sheila Gahagan, a Developmental-Behavioral pediatrician and epidemiologist who holds the Martin T. Stein Endowed Chair in Developmental-Behavioral Pediatrics, leads the division of 22 faculty members, 8 adjunct faculty members, and 3 developmental-behavioral pediatric fellows. The Division also has 27 research and health promotion staff, over half with advanced degrees. The division s four-fold clinical mission is to provide: 1) a medical home from birth through adolescence including for those with complex chronic conditions; 2) consultative care to promote breast feeding including for premature infants; 3) evidence-based developmental-behavioral pediatric evaluation and treatment to children from birth to 21-years old; and 4) care for adolescents with eating disorders, acute and chronic conditions, and sexual/reproductive health needs. The research focus includes childhood obesity, early life risk for cardiovascular disease, long-term consequences of infancy iron deficiency anemia, and early life developmental origins of disease focusing on biological and environmental determinants of disease. In addition, we work to understand and test interventions for a range of common health problems related to community conditions and health disparities. Educating undergraduate students, medical students, pediatric residents, fellows in developmental-behavioral pediatrics, child psychiatry, and post-doctoral research fellows is an important mission of the division. The division s combined clinical, research, and educational efforts continue in collaboration with local and global partners, including San Diego-based community clinics, health agencies and community organizations, and vibrant academicresearch partnerships locally, across the U.S., and in Chile and Mexico. Sheila Gahagan, MD, MPH Professor of Clinical Pediatrics Division Chief Developmental- Behavioral Pediatrics Bretten D. Pickering, MD Clinical Professor & Section Chief, General Academic Pediatrics Yi Hui Liu, MD, MPH Assistant Clinical Professor ; Section Chief, Developmental- Behavioral Pediatrics Eyla Boies, MD Clinical Professor General Academic Pediatrics Adam Braddock, MD Staff Physician General Academic Pediatrics Developmental- Behavioral Pediatrics 22 Faculty 27 Research Staff DIVISION FAST FACTS $5.2 Million in Major Research Grants MAJOR PLANS AND GOALS International Partnerships in Mexico and Chile Janet Crow, MD Associate Clinical Professor General Academic Pediatrics Sandra Daley, MD Clinical Professor Center for Community Health Associate Chancellor, UC San Diego Patricia East, PhD Research Scientist Center for Community Health Nancy Graff, MD Clinical Professor General Academic Pediatrics Kimberly Leek, MD Assistant Clinical Professor General Academic Pediatrics To provide a Medical Home to a diverse panel of patients including those with chronic medical or behavioral health problems and to provide a Medical Home for medically fragile pediatric patients To expand our comprehensive health care services to support young adults with chronic conditions in their transition to medical providers who care for adult patients Leah Kern, MD, MPH Assistant Clinical Professor General Academic Pediatrics Maya Kumar, MD Staff Physician General Academic Pediatrics/Adolescent Medicine Karen Loper, MD Associate Clinical Professor Medical Director, Adolescent Medicine Kyung Rhee, MD, MA, MSc Associate Professor Medical Director, Medical Behavior Unit Martin T. Stein, MD Professor Emeritus Developmental- Behavioral Pediatrics To collaborate with other clinical researchers to improve quality of care and advance medical understanding of pediatric diseases To provide outstanding educational experiences for medical students, residents and fellows. In addition, continue collaboration with University of San Diego Department of Marriage and Family Therapy to provide therapy to our patients and families and to facilitate communication between physical and mental health providers. Howard Taras, MD Clinical Professor Center for Community Health Tasha K. Taylor, MD Staff Physician Developmental- Behavioral Pediatrics Lori Wan, MD Clinical Professor General Academic Pediatrics Internal Medicine-Pediatrics Residency Program Director Lindia Willies-Jacobo, MD Clinical Professor General Academic Pediatrics Assistant Dean for Diversity & Community Partnerships, UCSD School of Medicine 16 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 17

10 GENERAL ACADEMIC PEDIATRICS & ADOLESCENT MEDICINE The Section of General Academic Pediatrics/Adolescent Medicine staffs the only academic primary care pediatric office for children residing in San Diego County and provides the main clinical general pediatric teaching site for University of California, San Diego (UCSD) medical students and pediatric residents. FACULTY PROFILE Lori Wan, MD Director, UCSD Internal Medicine-Pediatrics Residency Program Attends in the General Academic Pediatrics Clinic Attends in the General Internal Medicine Clinic Lindia Willies-Jacobo, MD Attends in the UCSD General Academic Pediatrics Clinic Assistant Dean for Diversity and Community Partnerships, UCSD School of Medicine The General Academic Pediatrics Division is responsible for the primary health care of all children seen at the UCSD Pediatric Clinic. The Pediatric Clinic and the Adolescent Medicine Clinic are located on the Rady Children s Hospital- San Diego (RCHSD) campus. With over 20,000 visits from children residing throughout San Diego, Riverside and Imperial Counties, the division strives to provide all patients with a medical home that is accessible, continuous, comprehensive, culturally effective, compassionate, and family-centered. CLINICAL ACTIVITIES Pediatric clinical services include: primary care and sports physicals, immunizations, assessment for behavioral problems, learning difficulties and eating disorders; pregnancy prevention/family planning; domestic/interpersonal violence; STD/HIV testing and counseling; evaluation and intervention with drug/alcohol problems; depression/ suicide interventions; and referrals to specialists and community services. Our newest clinical program is a Pediatric Travel Clinic, the only one in San Diego County. The Adolescent Medicine health care team recognizes that adolescence is a special time associated with particular physical and mental health concerns, requiring specially-trained professionals. The faculty in the Adolescent Medicine Program are board certified in adolescent medicine and distinguished by their specialty interest and training. In the Adolescent Medicine Clinic, specialists in Adolescent Medicine provide health care maintenance, contraception, illness care, and behavioral health counseling. At Rady Children s Hospital, Inpatient Medical Behavior/Eating Disorders Unit (MBU), Adolescent Medicine physicians collaborate with the UCSD Division of Child and Adolescent Psychiatry and the UCSD Eating Disorders Center for Treatment and Research. They offer a range of treatment options for teens and adults with Anorexia Nervosa and Bulimia Nervosa. Each individual receives a comprehensive evaluation that determines their individualized treatment plan. The physicians on the MBU have unique training in the medical management of teenagers and young adults with eating disorders requiring hospitalization. Following hospitalization, these patients can be followed medically in the Adolescent Medicine Clinic. Adam L. Braddock, MD Attending in UCSD general pediatrics clinic, developmental behavioral pediatrics clinic, Down syndrome clinic and San Ysidro Health Center developmental-behavioral pediatrics clinic Volunteer physician, International Health Collective Eyla Boies, MD Attends in the UCSD General Academic Pediatrics Office Medical Director, Premature Infant Nutrition Clinic 18 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Integrates medical student and resident education, as well as clinical research on breastfeeding Course Coordinator for PEDS 431 Ambulatory Pediatric Sub-internship Janet Crow, MD Attends in the UCSD General Academic Pediatrics Clinic Attends in the UCSD Medical Center, Newborn Nurse Nancy Graff, MD Cares for patients in the UCSD General Academic Pediatrics Office Pediatric consultant for North County Assessment Center Kim Leek, MD Attends in the UCSD General Academic Pediatrics Office Pediatric Resident Rotation Coordinator Continuity Clinic Director for UCSD Pediatrics Residency Leah Kern, MD Attends in the UCSD General Academics Pediatrics Clinic Director of the Pediatric Clerkship Rotation at UCSD General Academics Pediatrics Clinic Director of UCSD Pediatrics Travel Clinic Attends at the UCSD Pediatrics HIV Clinic Maya Kumar, MD Medical attending on the RCHSD inpatient eating disorder unit Medical Attending in the UCSD Adolescent Medicine Clinic Certified provider of long-acting contraception (Nexplanon) for adolescents Karen S. Loper, MD Medical Director UCSD Adolescent Medicine Clinic Medical attending for RCHSD inpatient eating disorder unit Pediatric consultant for Child & Adolescent Inpatient Psychiatry Service Bretten D. Pickering, MD Section Chief, Academic General Pediatrics/Adolescent Medicine Medical Director and Attending/UCSD General Academic Pediatrics Clinic Medical Director, Special Needs Clinic at RCHSD Attending at Helen Bernardy Center for Medically Fragile Children Eyla Boies, MD Clinical teaching with pediatric residents, medical students Continuity clinic preceptor Teaches lactation physiology and breastfeeding support Course Coordinator, 4 th year Medical Student Pediatric Ambulatory Sub-internship, Peds 431 Instructor What Every Physician Needs to Know Course Annual Academy of Breastfeeding Medicine Meeting Webinar presenter for AAP CA 3. Immunization, Everything You Wanted to Know but Were Afraid to Ask, a General Pediatrician s Perspective Webinar presenter - AAP. Maintaining Breastfeeding Beyond the First Week Adam L. Braddock, MD Clinical teaching of medical students, residents, continuity clinic residents, and journal club Problem based learning course group leader Practice of Medicine course group leader for 1 st year medical students Janet Crow, MD Teaches medical students and residents in patient care, journal club and small discussion groups Continuity clinic preceptor Regular Lecturer, UCSD/San Ysidro Family Medicine Residency Nancy Graff, MD Teaches medical students, residents in UCSD Pediatric Clinic Continuity clinic preceptor for pediatric residents Small group leader for 4 th year Medical Student course Principles to Practice Rotation Director for resident education in Community Pediatrics, including 4-week block rotation, Cultural Immersion Days, Film Nights and Theater Nights over 3 yrs of residency Coordinator for Resident Advocacy Education for AAP Lobby day annually in Sacramento Kimberly Leek, MD Teaches medical student, residents, and dental residents in General Pediatric clinic Lectures in the Clinic Morning Lecture Series Coordinator for Pediatric Resident Clinic RotatioN Director if the Continuity Clinic Program Coordinator of Continuity Clinic Educational Curriculum Leah Kern, MD Teaches medical student, residents, and dental residents in our clinic Lectures in the Clinic Morning Lecture SeriesCoordinator TEACHING ACTIVITIES for Pediatric Resident Clinic RotationDirector of the Continuity Clinic Program Coordinator of Continuity Clinic Educational Curriculum Maya Kumar, MD Clinical teaching for medical students in outpatient adolescent health care Clinical teaching for residents in the care of medically fragile eating disorder inpatients Regular didactic teaching in adolescent medicine for medical students and residents (Academic General Pediatrics morning and RCHSD Noon conferences, RCHSD Morning Report) Lecturer Medical complications of eating disorders - UCSD Psychology 134 course Develops adolescent medicine online teaching modules for residents continuity clinic Karen S. Loper, MD Board Certified Adolescent Medicine Coordinates Adolescent Medicine MS-4 elective Provides introductory lecture in Adolescent Health for Pediatrics during MS3 core rotation Medical student Independent Study Project Chair and trainee advisor UCSD School of Medicine Faculty for Problem-Based Learning Pediatric resident Clinical Pathology Case lecture supervisor Bretten D. Pickering, MD Teaches Pediatric primary care of medically fragile children to medical students and residents Participates in the 2 nd year Medical Student Introduction to Clinical Medicine course Faculty supervisor, UCSD School of Medicine MSTP Objective Structured Clinical Examination UCSD Physician Assessment and Clinical Education Program, Pediatric Coordinator Pediatric resident Clinical Pathology Case lecture supervisor Lori Wan, MD Program Director - UCSD Internal Medicine-Pediatrics Residency Teaches clinical pediatrics and internal medicine to residents. Faculty supervisor, Internal Medicine-Pediatric residents Faculty supervisor, UCSD School of Medicine MSTP Objective Structured Clinical Examination Faculty facilitator/small group leader, UCSD School of Medicine Interprofessional Team Training 3 rd -year medical students Facilitator/small group leader, UCSD School of Medicine How to present a History and Physical Examination 3 rd -year medical students Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 19

11 Lori Wan, MD, continued Faculty facilitator/small group leader, Principle to Practice course 4 th -year medical students Lindia J. Willies-Jacobo, MD Assistant Dean for Diversity and Community Partnerships Focus on teaching culturally competent pediatric health care Teaches clinical pediatrics to medical students, residents and continuity residents Course director - UCSD Program in Medical Education - Health Equity Eyla Boies, MD Actively involved in breastfeeding clinical research. Dr. Boies works with a board certified lactation consultant to provide nutritional, medical, and lactation follow-up for recently discharged preterm infants and their mothers in the Premature Infant Nutrition Clinic (PINC). Almost 800 infants have been seen in the PINC since opening almost eight years ago. She studies outcomes of infants and mothers seen in PINC through research on Quality Improvement approved by the UCSD Human Research Protections Program. Co-investigator on a community research study of knowledge, skill and attitudes of physicians related to provision of breast milk to former premature infants after hospital discharge. Principal investigator - Research to better understand parents decisions regarding childhood immunizations, Factors Influencing Parental Childhood Vaccination Decisions: A Social-Ecological Perspective and an AAP sponsored HPV Vaccine Education and Promotion Grant to improve parental acceptance of the HPV vaccine. Leah Kern, MD Principal Investigator - UCSD Pediatric Universal Lipid Screening Quality Improvement Project, a project to evaluate the impact of a QI initiative on lipid screening among 9-11 year olds. Maya Kumar, MD Participates in research on the medical management of eating disorders in an inpatient setting including patients with a history of overweight or obesity. She has presented her work at international meetings. Co-investigator on quality improvement project to improve HPV vaccine promotion among general pediatricians in Southern California. Contributor to case reports discussing challenging cases in adolescent medicine RESEARCH SUPPORT Nancy Graff, MD $19,685 American Academy and Allstate Foundation Teen Safe Driving Grant Nancy Graff, MD 2012 $1000 American Academy Community Pediatrics Training Initiative Advocacy Training Grant Eyla Boies, MD 03/16/ /15/ 2013 $15,500 UCSD Clinical and Translational Research Institute 20 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report RESEARCH ACTIVITIES Course director SOMI 233 Influences on Health: From Genes to Communities Course director SOMI 234 Beyond the Bench and Bedside: Partnering with CommunitieS Course director SOMI 235 Healthy Minds, Healthy Bodies Course director PEDS 229 Cognitive Strategies Course director SOMI 230 DOC-for-a-Day Small group leader for 4 th year Medical Student course Principles to Practice Academic Community Pilot Funding Program Premature Infant Nutrition Post-discharge Collaborative Project PUBLICATIONS Braddock, A. Children as research partners in community pediatrics. In: The Future of Human Subjects Research Regulation, I. Glenn Cohen and Holly Fernandez Lynch, eds., MIT Press, Kern L, Edmonds P, Perrin EC, Stein MT. An 8-year-old biological female who identified herself as a boy: perspectives in primary care and from a parent. J Dev Behav Pediatr 35: , Horikawa YT1, Udaka TY, Crow JK, Takayama JI, Stein MT. Anxiety associated with asthma exacerbations and overuse of medication: the role of cultural competency. J Dev Behav Pediatr Feb-Mar;35(2): doi: / DBP Kumar MM, Cowan HR, Erdman L, Kaufman M, Hick KM. Reach Out and Read is feasible and effective for adolescent mothers: A pilot study. Maternal and Child Health Journal, 2015; 19(11): doi /s Iyer S, Kumar M, Reiff MI, Stein M. Inattentive ADHD, stimulant medication and eight loss in a 15 year old girl: Are we enabling the development of an eating disorder? Jour Develop Behav Pediatrics, 2015; 36(7): Kumar MM, Nisenbaum R, Barozzino T, Sgro M, Bonifacio HJ, Maguire JL. Housing and sexual health among street-involved youth. Journal of Primary Prevention, 2015; 36(5): AWARDS & HONORS Adam L. Braddock, MD Advocacy Training Scholarship, American Academy, 2014 Eyla Boies, MD UCSD Academy of Clinician Scholars San Diego Top Doctors 2010, 2011, 2012, 2013, 2014, 2015 Board of Directors, Academy of Breastfeeding Medicine Board of Directors, San Diego County Breastfeeding Coalition Nancy Graff, MD 2012-present American Academy (national), Member - Committee on State Government Affairs Bretten D. Pickering, MD UCSD Academy of Clinician Scholars San Diego Top Doctors, 2010, 2011, 2012 Lindia Willies-Jacobo, MD UC San Diego Medical Education-Office of Diversity Award Nominee Women Who Mean Business Award: San Diego Business Journal AMSA Local Golden Ave Apple Award (Education and Advocacy) Lori Wan, MD San Diego s Physicians of Exceptional Excellence Top Doctors 2006, 2012, 2013 Nominee Kaiser Excellence in Teaching Award by UCSD medical students, 2011, 2013 Janet Crow, MD Project Leader AAP CA-Chapter 3 sponsored MOC Part 4 project," Pediatricians and Parents Together" using Ages and Stages in Pediatric Practices in San Diego to improve early detection of and referral for children with developmental delays and on-going DEVELOPMENTAL-BEHAVIORAL PEDIATRICS In 2015, Developmental-Behavioral Pediatrics (DBP) moved its consultation services to a beautiful clinic at 7910 Frost Street, and increased its patient volume and days of clinic coverage. In addition, DBP provides care for children at Rady Children s Hospital-San Diego (RCHSD) Autism Discovery Institute, the San Diego Regional Center, and San Ysidro Health Centers. We provide multidisciplinary clinical services at the Fetal Alcohol Spectrum Disorders Clinic and the Down Syndrome Clinic. Developmental-Behavioral Pediatrics provides education for pediatric and internal medicine/pediatric residents during their RRC-required DBP one-month block rotation. In addition, medical students rotate through DBP during their core pediatric clerkship and may take a clinical elective in DBP during their fourth year. We provide didactic teaching during the core curriculums for medical students and residents. The three-year ACGME-accredited DBP fellowship began July 1, 2011 and has graduated 3 fellows. The program consists of one intensive clinical year and two years focusing primarily on research and scholarly preparation for an academic career. Our fellowship program was awarded the highly competitive HRSA, Maternal Child Health Bureau grant for Leadership in Education in Developmental-Behavioral Pediatrics (07/01/ /30/2018). Our program has a strong focus on DBP in health disparity populations with specific emphasis on the U.S.-Mexico border population and military families. Our goal is to train the next generation of leaders in our field. Sheila Gahagan, MD, MPH Provides developmental-behavioral pediatric services in Developmental-Behavioral pediatric consultation clinic, Fetal Alcohol Syndrome Clinic, Down Syndrome Clinic Consults nationally and internationally on developmentalbehavioral pediatrics Yi Hui Liu, MD, MPH Administers Developmental-Behavioral Pediatric clinical services Provides developmental-behavioral pediatric services in Developmental-Behavioral pediatric consultation clinic Provides care and consultation for children with developmental disabilities through San Diego Regional Center Oversees education for medical students, residents and Developmental-Behavioral Pediatric and Child Psychiatry fellows PUBLICATIONS Liu YH, Pesch, MH, Lumeng JC, Stein MT. Pica in a Four-Year-Old Girl with Global Developmental Delay. Journal of Developmental & Behavioral Pediatrics 2015; 36: Garland A, Taylor R, Brookman-Frazee L, Baker-Ericzen M, Haine-Schlagel R, Liu YH, Wong S. Does Patient Race/Ethnicity Influence Provider Decision-Making for Diagnosis and Treatment of Childhood Disruptive Behavior Problems? Journal of Racial and CLINICAL ACTIVITIES Martin T. Stein, MD Provides developmental-behavioral pediatric clinical services in consultation clinic RESEARCH ACTIVITIES Tasha Taylor, MD Practicing Developmental-Behavioral Pediatrician at the San Ysidro Health Center (SYHC), a federally-funded community health center on the border with Tijuana, Mexico. She manages the Child Development Clinic within the SYHC, where evaluations and ongoing care is provided to children referred for developmental delays, Autism, ADHD, learning disabilities, anxiety/depression and behavioral concerns. Ethnic Health Disparities 2015; 2: DOI /s Gahagan S, Liu YH, Brown S: Crying and Colic. In Marcdante KJ, Kliegman RM (eds). Nelson Essentials, 7 th Edition. Saunders Elsevier Gahagan S, Liu YH, Brown S: Temper Tantrums. In Marcdante KJ, Kliegman RM (eds). Nelson Essentials, 7 th Edition. Saunders Elsevier Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 21

12 Gahagan S, Liu YH, Brown S: Attention-Deficit/Hyperactivity Disorder. In Marcdante KJ, Kliegman RM (eds). Nelson Essentials, 7 th Edition. Saunders Elsevier Gahagan S, Liu YH, Brown S. Control of Elimination. In Marcdante KJ, Kliegman RM (eds). Nelson Essentials, 7 th Edition. Saunders Elsevier Gahagan S, Liu YH, Brown S. Normal Sleep and Pediatric Sleep Disorders. In Marcdante KJ, Kliegman RM (eds). Nelson Essentials, 7 th Edition. Saunders Elsevier Gist L, Stein MT. Book Review: Developmental screening in your community: an integrated approach for connecting children (Paul Brooks Publishing Co, 2013) in Journal of Developmental & Behavioral Pediatrics 35: 469; Stein MT. Developmental issues in Audio Digest Pediatrics Board Review. July Stein MT. Commentary on Coker TR et al. Well-child care clinical practice redesign for serving low-income children. Yearbook of Pediatrics 2015 Philadelphia: Elsevier, Horikawa YT, Udaka TY, Crow JK, Takayama JI, Stein MT. Anxiety associated with asthma exacerbation and overuse of medication: the role of cultural competency. Journal of Developmental & Behavioral Pediatrics 34; ; Kern L, Edmonds P. Perrin EC, Stein MT. An 8- year old biological female identifies herself as a boy: perspectives in primary care and from a parent. Journal of Developmental & Behavioral Pediatrics 34; Stein MT, O Dea T, Snyder D, Dixon SD. Sailing with Young Children: Risk or Adventure? Journal of Developmental & Behavioral Pediatrics 35: 408-9; Hamilton DR, Stein MT, Wolraich M. Doctor-patient relationships: Current status and projections for the future. Journal of Developmental & Behavioral Pediatrics 35; ; Van Niel C, Pachter LM, Wade Jr R, Felitti VJ, Stein MT. Adverse events in children: predictors of adult physical and mental conditions. Journal of Developmental & Behavioral Pediatrics 35: ; Stein DS, Welchons, LW, Corley KB, Dickenson H, Levin AR, Nelson, CA, Stein MT. Autism associated with early institutionalization, high intelligence, and naturalistic behavior therapy in a 7 year-old boy. Journal of Developmental and Behavioral Pediatrics 36:53-55; Gist L, Mathews C, Williams KN; Stein MT. A 9-Year-Old Girl With Persistent Obsessive and Compulsive Behaviors in a Primary Care Pediatric Practice. Journal of Developmental & Behavioral Pediatrics (2015) 36:3. O'Brien JS, Taras H, Barton S, Stein MT. Behavioral Changes Associated with a Disruptive New Student in the Classroom (2015) Journal of Developmental & Behavioral Pediatrics. 36(5): Iyer S, Kumar M, Reiff, MI, Stein MT. Attention-Deficit/ Hyperactivity Disorder, Stimulant Medication, and Weight Loss in a 15-Year-Old Girl: Are We Enabling the Development of an Eating Disorder? Journal of Developmental & Behavioral Pediatrics (2015) 36(7) Liu YH, Pesch MH, Lumeng JC, Stein MT. Pica in a Four-Year-Old Girl with Global Developmental Delay. Journal of Developmental & Behavioral Pediatrics (2015) 36(9) Stein MT. Journal Watch Pediatric Adolescent Medicine (New England Journal Medicine Publication): 2-3 articles each month, Stein MT. Commentary: Group-based parenting skill training in primary care offices: are we ready for the challenge? JAMA Pediatrics. 2014;168(1): UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 23

13 CENTER FOR COMMUNITY HEALTH The focus of The Center for Community Health is on health disparities in children and youth, their families and the communities in which they live. Our work includes clinical, epidemiological and community-based research and local health promotion projects. We have funding from the National Institutes of Health, American Heart Association, Centers for Disease Control and Prevention, The San Diego County Health and Human Services Agency Centers for Disease Control and Prevention, The San Diego County Health and Human Services Agency, the Network for a Healthy California Foundation and other foundations, totaling $2,203,968 over the last two years (including total awards for grants in which we are the PIs). In , our areas of focus included childhood obesity and later health outcomes, effects of infant nutrition on health and development, health promotion. Dr. Rhee is a pediatric hospitalist with special interest in childhood eating and weight related disorders. Specifically, she conducts research on the behavioral, cognitive and biologic factors contributing to the development and management of childhood obesity. Her work focuses on identifying novel targets for obesity prevention and treatment including, parenting styles, parent feeding behaviors, child eating behaviors, executive functioning, genetic and epigenetic influences, and gut peptides and the microbiome. (Total Dollar amount of funding - $1,200,501) FACULTY PROFILES Howard Taras, MD Provides medical consultation to school districts, public and private, across southern California, with a concentration in San Diego County This includes evaluating student s health care needs, establishing school health care plans, and supervising select school nursing services Sandra Daley, MD Principal Investigator of the Health Career Opportunities Program and the Hispanic Center of Excellence. Educational activities include: recruitment and retention of students and faculty from disadvantaged groups; establishing partnerships with community groups and schools of higher education; teaching and mentoring students, fellows and junior faculty; and designing and implementing academic enrichment and research training programs for post-baccalaureate, community college, middle and high school academic enrichment and research methodology training programs Supervises medical students Independent Study Projects (ISP) Program advisor for the Healthcare Opportunities Preparation Empowerment Program (HOPE), UCSD Diversity Coalition, and the School of Public Health course, Special Topics in Health Disparities Patricia East, PhD Provides research guidance to two Public Health graduate students (Erin Delker, doctoral student, Public Health; Dong-Jin E. Kang- Sim, Ph.D. candidate, Public Health), and our visiting scholar, Dr. Monica Vasconcelos Taught course, Research and Evaluation Methods, at San Diego State University, Fall, 2014 (Child Development and Family Studies Department, CFD370). Sheila Gahagan, MD, MPH Core faculty for the Community Pediatric rotation (attends two months/ yr) Mentor and thesis committee member for Doctoral level students in Public Health Health Behavior (Kim Tran Carpuic, PhD candidate, ; Kristi Robusto, PhD candidate, ; Kyle 24 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report CLINICAL ACTIVITIES TEACHING ACTIVITIES Gutzmer, PhD candidate, 2015-present), Public Health Global Health (Eastern Kang Sim, PhD Candidate, 2012-present), Public Health Epidemiology (Ann Von Holle, University of North Carolina Chapel Hill; Lorena Pacheco, 2015-present) Mentor for DBP fellows Scott Brown ( ), Chadley Huebner ( ), Lauren Gist ( ), Kris Kazlauskas ( ), Sai Iyer ( ), Theodora Nelson ( ) Mentor for AGP fellow Lisa Mondzelewski ( ) Mentor for Pediatrics resident, Helen Wang (2015) Mentor for Medical student independent research projects (Kim Khuc, ; Carolyn Sawyer 2013; Sonia Singh 2013; July Lee 2014; Jessica Cheng 2014; Elissa Kim GloCal Fellowship Mentor for Undergraduate level students (Armand Harb 2013; Karen Herrera 2013; Jacqueline Doan 2015; Akash Rajaratnam , Raven Odom 2015 University of Michigan) Mentor, Pediatric Hematology-Oncology Fellow, Paula Aristizabal Regular faculty at French Developmental-Behavioral Pediatrics annual course Nancy Graff, MD Rotation director for Community Pediatrics Rotation-Resident training in community pediatrics, advocacy, and child protection, including developing and implementing quarterly Cultural Immersion Days and three film nights and one theater night per year; Leads two noon conferences in Community Pediatrics Medical Student-4 course Principles to Practice: small group facilitator for general pediatrics cases; Directs the adolescent medicine case session and was small group facilitator Teaches continuity clinic residents in General Pediatrics Kyung (Kay) Rhee, MD, MA, MSc Teaches in the pediatric hospitalist medicine curriculum to pediatric hospitalist fellows Leads monthly research working group meetings for the fellows in the Division and Hospitalist Medicine as well as Developmental-Behavioral Pediatrics Mentor and supervisor in the UCSD Faculty Mentor Program (Stanny Goffin, Elisa Legallet, Erica Settlecowski, 2015) Supervises graduate students and post-doc students in Psychology and Marriage and Family Therapy in delivering behavioral weight control intervention Faculty advisor for the Community Pediatrics Rotation Attending physician for 2 blocks per year Faculty small group leader in SOM EBMI (Epidemiology/ Biostatistics/Medical Informatics) course Primary Mentor for medical students in Independent Study Projects (ISP) (Mimi Nguyen-2013, Scott Sutton-2013, Hui Sandra Daley, MD Recruitment, development, enrichment, & retention program for Hispanic students and faculty Promoting factors to increase qualified disadvantaged students entering the pipeline to become part of the local healthcare workforce Understanding and addressing SES, racial and ethnic disparities related to training health professionals Patricia East, PhD Family- and individual-level factors that contribute to how younger siblings of pregnant teens can avoid teenage parenting (this is the only longitudinal study in the country to focus on siblings risk of adolescent pregnancy and to examine family adaptation to adolescent transition to parenting) Risk factors for sexual and dating violence victimization The link between early parenthood and new onset obesity The long-term effects of iron deficiency and iron-deficiency anemia in infancy for adjustment in middle childhood and adolescence The temporal precedence between childhood obesity and motor skills Effects of Somali refugee mothers past trauma on their children Sheila Gahagan, MD, MPH Research is aimed at understanding health disparities in child growth and development Howard Taras, MD Research in practical applications of school health PUBLICATIONS East, PL. Cohesive, trusting communities buoy at-risk youth throughout adolescence. J Adol Health, 53(1): 1-2 DOI: /j. jadohealth Published: JUL (Invited editorial). East, PL. Hamill, SB. Sibling caretaking among Mexican American youth: Conditions that promote and hinder personal and school success. Hispanic J Beh Sci, 35(4): , East, PL., & Barber, JS. High educational aspirations among pregnant adolescents are related to pregnancy unwantedness and subsequent parenting stress and inadequacy. J Marr & Family, 76: , Yeung-2015), and secondary advisor for medical students completing an ISP project (Sonia Singh-2013, Ethan Mathews (2014) per year. Primary Mentor, Preventative Medicine Resident- Deepa Sanidhi, MD Howard Taras, MD Core faculty for the Community Pediatric rotation (11 months per year of teaching; one month of precepting) Oral health training session, monthly for 10 months per year to medical students Supervises medical students Independent Study Projects Teaches school health to all pediatric residents, and to undergraduates in UCSD Teacher Education Program Teachers oral health disparities annually to PRIME Medical Students RESEARCH ACTIVITIES East, PL., & Hokoda A. Risk and protective factors for sexual and dating violence victimization: A longitudinal, prospective study of Latino and African American adolescents. J Youth & Adol, 44(6): , Lee, J., East, P., Blanco, E., Kang-Sim, E., Castillo, M., Lozoff, B., & Gahagan, S. Early parenthood linked to new onset overweight or obesity among Chilean adolescents. Int J Adol Med & Health, 2015 (online early). Rose O, Blanco E, Martinez S, Kang-Sim E, Castillo M, Lozoff B, Vaucher Y, Gahagan S, Developmental Scores at 1 Year With Increasing Gestational Age, Weeks. Pediatrics May;131(5):e doi: /peds Epub 2013 Apr 15. PMID: PMCID:PMC Reyes M, Hoyos V, Martinez S, Lozoff B, Castillo M, Burrows R, Blanco E, Gahagan S. Satiety responsiveness and eating behavior among Chilean adolescents and the role of breastfeeding. Int J Obes (Lond) Apr;38(4): doi: /ijo PMID: Martinez SM, Blanco E, Delva J, Burrows R, Reyes M, Lozoff B, Gahagan S. Perception of Neighborhood Crime and Drugs Increases Cardiometabolic Risk in Chilean Adolescents. J Adolesc Health Jun;54(6): doi: /j.jadohealth PMID: Bender MS, Clark MJ, Gahagan S. Community Engagement Approach: Developing a Culturally Appropriate Intervention for Hispanic Mother-Child Dyads. J Transcult Nurs. Oct 2014; 25(4): PMID: Williams CB, Mackenzie KC, Gahagan S. The Effect of Maternal Obesity on Offspring. Clin Obstet Gynecol 2014 Sep; 57(3): PMID: Ayala, G.X., Ibarra, L., Binggeli-Vallarta, A., Moody, J., McKenzie, T.L., Angulo, J., Hoyt, H., Chuang, E., Ganiats, T.G., Gahagan, S., Ji, M., Zive, M., Schmied, E., Arredondo, E., Elder, J.P. Our Choice/ Nuestra Opción: the Imperial County, California, Childhood Obesity Research Demonstration study(ca-cord). Childhood Obesity (Print). 2015; 11(1): PubMed [journal] PMID: , PMCID: PMC Aristizabal P, Singer J, Cooper R, Wells KJ, Nodora J, Milburn M, Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 25

14 Gahagan S, Schiff DE, Martinez ME. Participation in pediatric oncology research protocols: Racial/ethnic, language and age-based disparities. Pediatric blood & cancer. 2015; 62(8): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Brown SJ, Rhee KE, Gahagan S. Reading at Bedtime Associated with Longer Nighttime Sleep in Latino Preschoolers. Clinical Pediatrics. 2015; PubMed [journal] PMID: Burrows R, Correa-Burrows P, Reyes M, Blanco E, Albala C, Gahagan S. High cardiometabolic risk in healthy Chilean adolescents: associations with anthropometric, biological and lifestyle factors. Public health nutrition. 2015; :1-8. NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Reyes M, Quintanilla C, Burrows R, Blanco E, Cifuentes M, Gahagan S. Obesity is associated with acute inflammation in a sample of adolescents. Pediatric Diabetes. 2015; 16(2): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Burrows R, Correa-Burrows P, Reyes M, Blanco E, Albala C, Gahagan S. Healthy Chilean Adolescents with HOMA-IR 2.6 Have Increased Cardiometabolic Risk: Association with Genetic, Biological, and Environmental Factors. Journal of Diabetes Research Epub ahead of print. Article ID BOOK CHAPTERS Gahagan S, Liu Y, Brown S, Crying and Colic. In Marcdante KJ, Kliegman RM (eds): Nelson Essentials, 7 th Edition. Saunders Elsevier. 2014: Gahagan S, Liu Y, Brown S, Temper Tantrums. In Marcdante KJ, Kliegman RM (eds): Nelson Essentials, 7 th Edition. Saunders Elsevier. 2014: Gahagan S, Liu Y, Brown S, Attention-Deficit/Hyperactivity Disorders. In Marcdante KJ, Kliegman RM (eds): Nelson Essentials, 7 th Edition. Saunders Elsevier. 2014: Gahagan S, Liu Y, Brown S, Control of Elimination. In Marcdante KJ, Kliegman RM (eds): Nelson Essentials, 7 th Edition. Saunders Elsevier. 2014: Gahagan S, Liu Y, Brown S, Normal Sleep and Pediatric Sleep Disorders. In Marcdante KJ, Kliegman RM (eds): Nelson Essentials, 7 th Edition. Saunders Elsevier. 2014: Rhee KE, Phan TL, Barnes RF, Benun J, Wing RR. A Delayed- Control Trial Examining the Impact of Body Mass Index Recognition on Obesity-Related Counseling. Clinical Pediatrics. September 2013, Vol. 52, No. 9, pgs DOI: / Epub 2013 June 10. Rhee KE, Pan TY, Norman GJ, Crow S, Boutelle K. Relationship between maternal parenting and eating self-efficacy in overweight children when stressed. Eating and Weight Disorders Studies on Anorexia, Bulimia, and Obesity. September 2013; Vol. 18, Issue 3, pgs NIHMSID# DOI: /s x. PMC Martinez S, Rhee KE, Blanco E, Boutelle K. Maternal attitudes and behaviors regarding feeding practices in elementary-school age Latino children: A pilot qualitative study on the impact of the cultural role of mothers in the U.S.-Mexican border region of San Diego, California. Journal of the Academy of Nutrition and Dietetics. February 2014; Vol 114, No 2, pgs Epub 2013 Dec. 3. NIHMS Braden A, Rhee KE, Peterson CB. Rydell SA, Zucker N, Boutelle K. Associations between Child Emotional Eating and General Parenting Style, Feeding Practices, and Parent Psychopathology. Appetite Sept; 80: doi: /j.appet Epub 2014 Apr 26. Rhee KE, McEachern R, Jelalian E. Parent readiness to change differs for overweight child dietary and physical activity behaviors. Journal of the Academy of Nutrition and Dietetics. October 2014; Vol 114, No. 10, pgs DOI: /j.jand PMC Zive M and Rhee KE. Call to Action: Continuum of Care for Females of Reproductive Age to Prevent Obesity and Ensure Better Health Outcomes of Offspring through Nutrition. Clinical Obstetrics and Gynecology. September 2014; Vol 57; No. 3, pgs Rhee KE, Boutelle K, Jelalian E, Barnes R, Dickstein S, Wing R. Firm maternal parenting associated with decreased risk of excessive snacking in overweight children. Eating and Weight Disorders Studies on Anorexia, Bulimia, and Obesity doi: / s x. PMC Boutelle KN, Liang J, Knatz S, Matheson B, Risborough V, Strong D, Rhee KE, Craske MG, Zucker N, Bouton ME. Design and implementation of a study evaluating extinction processes to food cues in obese children: The Intervention for Regulation of Cues Trial (iroc). Contemporary Clinical Trials. 2014; DOI: /j. cct PMC Rhee KE, Dickstein S, Jelalian E, Boutelle K, Seifer R, Wing R. Development of the General Parenting Observational Scale to assess parenting during family meals. International Journal of Behavioral Nutrition and Physical Activity. 2015; 12:49. doi: /s PMC Brown SJ, Rhee KE, Gahagan S. Reading at bedtime associated with longer nighttime sleep in Latino preschoolers. Clinical Pediatrics Jul 15 (Epub ahead of print) doi: / Rhee KE. Approach to Fluid Management. Step-Up to Pediatrics. Eds. Shah, S., Alverson, B., Ronan, J. Lippincott Williams & Wilkins. Nov. 28, ISBN/ISSN: Rhee KE and Braden AL. What is motivational interviewing and how can I use it to help motivate my patients to lose weight? Curbside Consultation in Pediatric Obesity. Ed. Huang, JS. SLACK Inc ISBN: Braden AL and Rhee KE. What are the major social factors that contribute to childhood obesity, and how can clinicians and caregivers alter their impact? Curbside Consultation in Pediatric Obesity. Ed. Huang, JS. SLACK Inc ISBN: Non-Peer Reviewed Publications: Rhee, K. Baby fat? Families fighting obesity. International Innovation: Disseminating science, research and technology. Sept. 2013; Stein O Brien J, Taras H, Barton S, Sellick P, Stein MT. Behavior Changes Associated with a Disruptive New Student in the Classroom. J Dev Behav Pediatr : Taras HL, Contributing Editor. Academic achievement of children and adolescents with oral clefts. In Year Book 2015; Chapter 5; Dentistry and Otolaryngology (ENT); pp Elsevier Mosby Publications, Philadelphia, 2015 Morton L, Weinstein J, Taras H, Reznik V. Teaching Teamwork to Law Students, Journal of Legal Education 63:36-64 (2013), reprinted in Legal Education Digest, 2014; 22(1): Taras HL: Children (Chapter 12) in Feldman MD, Christenson JF (eds): Behavioral medicine: a guide for clinical practice, 4 th Ed. Lange Medical Books/McGraw Hill, Taras HL, Kalichman MW, Schulteis G, Dumbauld J, Bell Y, Seligman FF, West KD. Soliciting community views of health research: a prelude to conducting specific research projects; Health Expectations 2014; doi: /hex Ohno-Machado L, Agha Z, Bell DS et al Pscanner: patient-centered scalable National Network for Effectiveness Research. J Am Med Inform Assoc published online April 29, 2014; doi: / amiajnl Dumbauld J, Kalichman M, Bell Y, Dagnino C, Taras H. Case study in designing a research fundamentals curriculum for community health workers: a university-community clinic collaboration. Health Promotion Practice 2014; 15(1): Taras H, Haste NM, Berry AT Tran J, Singh RF. Medications at School: Disposing of Pharmaceutical Waste. Journal of School Health 2014; 84(3): doi: /josh Taras H, VonJaeger R. (2012) Clinical research: seniors making a difference ; Product ID # PZFWBF8 Dimitri C, Oberholtzer L, Zive M, Sandolo C. Enhancing food security of low-income consumers: An investigation of financial incentives for use at farmers markets. Food Policy Zive MM, Rhee KE. Call to action: continuum of care for females of reproductive age to prevent obesity and ensure better health outcomes of offspring through nutrition. Clin Obstet Gynecol. 2014, 57(3): Ayala GX., Ibarra, L, Binggeli-Vallarta A, Moody J, McKenzie TL, Angulo J, Hoyt H, Chuang E, Ganiats TG, Gahagan S, Ji M, Zive M, Schmied E, Arredondo EM, Elder JP. Our Choice/Nuestra Opcion: the Imperial County, California, Childhood Obesity Research Demonstration study (CA-CORD). Child Obes. 2015, 11(1): RESEARCH SUPPORT Sandra Daley, MD D18HP10623 Sept Aug $1,484,444 PHS (HRSA) "Health Careers Opportunity Program/S.D. Regional Consortium" D34HP18954 July 2013-June 2014 $719,524 PHS (HRSA), HRSA Hispanic Center of Excellence Sheila Gahagan, MD, MPH 1R01HL A2 (PI). Aug 1, 2008 Jul 31, 2013 $2,868,173 HHS, NHLBI. "Biological and Psychosocial Determinants of Adolescent Obesity/ Cardiovascular Risk" (PI) Apr 1, 2011 Dec 31, 2013 $40,000 UC, San Diego - Department, Division of Child Development and Community Health. The Gift of Health (El Regalo de Salud): Promoting optimal weight gain in first-time pregnant mothers and their babies. RM077M (PI) Jan 01, Dec 31, 2013 $9,980 UCSD - Academic Senate. Mother-Infant Obesity Prevention: "Using Social Media to Support Behavior Change in Pregnancy" 2R01HD (MPI) Jul 16, 2012 Jul 15, 2017 $2,422,037 NIH "Neuromaturational Delays in Iron Deficient Anemic Infants" T77MC (PI) Jul 1, 2013 Jun 30, 2018 $971,389 HRSA "Maternal Child Health Bureau. Leadership in Developmental Behavioral Pediatrics" R01 HL A1 (MPI) Sep 1, 2013 Aug31, 2016 $750,000 HHS, NHLBI "Fatty Acids, Adiposity & Cardiometabolic Risk in Adolescence" 2R01HL (PI). Sep 1, 2014 June 30, 2018 $2,016,054 HHS, NHLBI "Biological and Psychosocial Determinants of Adolescent Obesity/ Cardiovascular Risk" 15GRNT (MPI) Jul 1, 2015 Jun 30, 2017 $77,000 AHA "Genetic and Environmental Determinants of Obesity and Cardiovascular Risk across the Lifecourse: The Santiago Longitudinal Cohort Study" UCGHI GloCal Health (Co-I) Sep Aug 2017 Fogarty International Center (FIC) to provide global health research training opportunities for 9-12 fellows annually. 1R21ES (Co-I) Sep 1, 2015 Aug 31, 2017 $15,166 NIH/NIEHS "Pesticides and Mental Health among Adolescents in Ecuadorian Agricultural Communities" 1 U01 DK (Co-I) Aug 15, 2015 Jun 30, 2020 $140,775 NIH/NIDDK "Prevention of Lower Urinary Tract Symptoms (LUTS): Bladder Health Clinical Center UC San Diego Site" 1 U18DP (Consultant) Oct 1, 2011 Sep 30, 2015 $6,000 CDC "Imperial County Childhood Obesity Prevention Project 1R21HD A1 Dec 1, 2013 Nov 30, 2015 $6,000 HHA, NHLBI "Introducing Child Menus in Restaurants to Improve Access to Healthier Foods" Kyung Rhee, MD, MA, MSc K23HD PI) 6/5/09-5/31/14 $808,680 Eunice Kennedy Shriver NICHD "Role of Parenting skills, style and family functioning in pediatric weight loss" 1R01DK (Co-I) 6/1/12-5/31/17 $3,054,790 NIDDK "Learning theory to improve obesity treatments" R21 HD (PI) 12/5/13-11/30/15 $342,091 Eunice Kennedy Shriver NICHD "Promoting Child Inhibitory Control Skills around Food" USDA/Egg Nutrition Center-(Co-I) 3/1/14-2/28/16 $90,000 "A pilot study examining the impact of eggs for breakfast on weight loss and hunger in obese children" Rady Children s Academic Enrichment Fund (PI) 5/1/14 4/30/15 $49,730 "Probiotics and family-based behavioral therapy for pediatric weight loss" 26 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 27

15 RESEARCH SUPPORT Kyung Rhee, MD, MA, MSc, continued Department, UCSD (Co-PI) 1/1/14 12/31/15 "Preventing Emotional Eating RouTEENS (PEER): Obesity treatment for adolescent females who emotionally eat and their mothers" Howard Taras, MD 1UL1 RR July 2010-Mar $36,586,707 NIH Natl Ctr Research Resources, San Diego CTRI 1 U01 AA Sept Aug $10,545,402 NIH (NIAAA), Collaboration to Establish the Prevalence of FASD in San Diego, CA CDRN April 2014 October 2015 $6,994,451 PCORI, "Patient-Centered Scalable National Network for Effectiveness Research" County of San Diego July 2006 to June 2017 $285,000 "Dental Health Initiative; to educate child health professionals on oral health promotion" UL1TR August 2015 to March 2020 $7,963,176 San Diego Clinical & Translational Research Institute (CTRI) AWARDS & HONORS Sheila Gahagan, MD, MPH Academic Senate Research & Travel Award, University of California, San Diego, UCSD 2013, 2014, 2015 Kyung Rhee, MD, MA, MSc Academic Pediatric Association Research Award for Best Abstract by a Student (Mentor), Pediatric Academic Society Meeting UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 29

16 Allergy, Immunology & Rheumatology 30 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 31

17 INTRODUCTION The Division of Allergy, Immunology, and Rheumatology provides comprehensive clinical services for children with allergic, immunologic, rheumatologic diseases, and Kawasaki disease in outpatient and inpatient settings at a variety of venues throughout San Diego County. The division also maintains an internationally recognized research program in the areas of translational and clinical research in autoinflammatory disorders, genetics of rare inherited diseases, Kawasaki disease, food allergy, eosinophilic esophagitis, and basic research in T cell immunology and is currently building clinical research programs in pediatric rheumatology, severe asthma, and immunodeficiency. FACULTY DIVISION FAST FACTS Hal M. Hoffman, MD Professor & Medicine Division Chief Seema S. Aceves, MD, PhD Associate Professor Lori Broderick, MD, PhD Assistant Adjunct Professor Jane C. Burns, MD Professor in Residence Johanna Chang, MD Assistant Clinical Professor 45 years of serving San Diego County 4 Sattelite Offices $1.9 Million in Major Research Grants Internationally Recognized Research Programs MAJOR PLANS AND GOALS Peter Chiraseveenuprapund (Chira), MD, MS Associate Clinical Professor Alessandra Franco, MD, PhD Associate Adjunct Professor Bob Geng, MD Assistant Clinical Professor Susan S. Laubach, MD Assistant Clinical Professor Sydney Leibel, MD Assistant Clinical Professor To continue to provide cutting edge and compassionate care to patients with allergic, immunologic, and rheumatologic diseases as well as comprehensive and balanced clinical advice to pediatricians and specialists. We plan to expand our outreach to outlying underserved areas by taking advantage of telemedicine. To continue our tradition of outstanding translational research involving rare pediatric immune and inflammatory diseases including autoinflammatory diseases, Kawasaki s disease, eosinophilic esophagitis, and immunodeficiency while building stronger collaborations with academic and industrial researchers We aim to expand our clinical research programs in food allergy, severe asthma, immunodeficiency, and pediatric rheumatologic diseases while building our basic immunology research program To provide exceptional educational experiences for fellows, residents, medical students, and allied health providers. We also plan to expand our effort at community education about prevention and treatment of allergic, immunologic, rheumatologic diseases Stephanie Leonard, MD Assistant Clinical Professor Suhas Radhakrishna, MD Assistant Clinical Professor The Allergy Immunology Program was founded by Dr. Robert Hamburger, emeritus professor in the 1970s and was led by Dr. John Bastian for more than 20 years. Currently, the division has 7 physicians, 2 nurse practitioners, and a nurse specialist. The division has subspecialty clinics in immunodeficiency, recurrent fever, eosinophilic esophagitis, food allergy, and severe asthma. In 2014 we joined forces with a well respected private practice, the Allergy and Asthma Medical Group (AAMG) and added 3 affiliate physicians. Patients are seen at the main office at Rady Children s, and at satellite offices in Encinitas, Escondido, Oceanside and Murrieta and now AAMG. Robert M. Sheets, MD Clinical Professor CLINICAL ACTIVITIES Chisato Shimizu, MD Project Scientist The Pediatric Rheumatology Program began in 1994 by Dr. Ilona Szer with the establishment of a multidisciplinary team trained to care for children with a wide variety of rheumatic diseases, including arthritis, vasculitic diseases, and other autoimmune conditions. In addition to four experienced physicians, the division includes a 3 pediatric rheumatology nurses, a pediatric physical and occupational therapist, and a social worker. Patients are seen at the main office at Rady Children s, and at satellite offices in Encinitas, Escondido, Oceanside and Murrieta. 32 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 33

18 The Kawasaki Disease (KD) Research Center was formed in 1991 by Dr. Jane Burns and is devoted to the study and treatment of patients with KD. It is a one-of-a-kind Center providing 24/7 clinical coverage for KD patients and cutting edge clinical and translational research. Patients are seen at the main office at Rady Children s. Dr. Robert Sheets from the Pediatric Rheumatology program recently joined the KD Clinical Team. Seema S. Aceves, MD, PhD Directs a weekly combined pediatric allergy, immunology- gastroenterology clinic for the evaluation, treatment and research of patients with eosinophilic gastrointestinal disease (EGID), evaluating approximately 70 new patients per year Conducts immunology and allergy clinic allergy clinics in Murrieta and Rady Children s Hospital-San Diego (RCHSD) and provides inpatient consultation. Lori Broderick, MD, PhD Directs a pediatric recurrent fever clinic specializing in the evaluation, treatment and research of patients with autoinflammatory and non-infectious recurrent fever disorders, evaluating nearly 50 new patients per year with these rare disorders. Conducts immunology and allergy clinics at Rady Children s Hospital-San Diego (RCHSD) and provides inpatient consultatio Jane C. Burns, MD Directs the Kawasaki Disease Research Center at RCHSD that provides comprehensive inpatient and outpatient care for approximately 90 new inpatients per year. The dedicated Kawasaki Disease Clinic, directed by Dr. Burns, provides outpatient follow-up care for over 1,500 children who have recovered from Kawasaki disease Johanna Chang, MD Conducts pediatric rheumatology clinics in Encinitas and at RCHSD and provides inpatient consultation Conducts a multidisciplinary clinic with nephrology for patients withrheumatologic and renal disease Peter Chira, MD Conducts pediatric rheumatology clinic at RCHSD and at satellite locations (Escondido, Murrieta). Provides inpatient consultations at RCHSD. Lori Broderick, MD, PhD Teaches UCSD and Scripps allergy fellows, UCSD medicine and pediatric residents in allergy, immunology and fever clinics three days per month Mentors UCSD undergraduate, and pediatric residents in laboratory studies on genetics of rare diseases Teaches medical students, Internal Medicine and Pediatric residents and small group faculty leaders in Immunology courses at the UCSD School of Medicine. Teaches allergy and immunology to medical students, and Internal Medicine and Pediatric residents at hospital-based noon conferences and educational series. Physician Coordinator, for the UCSD/Rady Children s Bob Geng, MD Co-Director of the newly established Severe Pediatric Asthma Clinic Conducts General Pediatric Allergy & Immunology clinics at RCSHD and Combined Adult and Pediatric Allergy & Immunology clinics at the Allergy Asthma Medical Group Hal M. Hoffman, MD Conducts pediatric allergy and immunology clinics in Encinitas and at RCHSD and provides inpatient consultation Participates in Recurrent Fever clinic Susan S. Laubach, MD Conducts allergy and food allergy clinics at AAMG and immunology clinic at Rady Children s hospital and provides inpatient consultation Sydney Leibel, MD Co-Director of the newly established Severe Pediatric Asthma Clinic Conducts allergy clinics at Rady Children s Hospital and AAMG Conducts immunology clinic at Rady Children s hospital Stephanie Leonard, MD Directs the Food Allergy Center at Rady Children s Hospital/ UC San Diego, which was named a Clinical Center of Excellence and an inaugural member of the FARE Clinical Network in Dr. Leonard evaluates approximately 400 new food allergy patients per year. Conducts food allergy, general allergy/asthma and immunology clinics at RadyChildren s Hospital and Encinitas satellite (over 1,700 patients per year) and provides inpatient consultation Suhas Radhakrishna, MD Conducts pediatric rheumatology clinics at Rady Children s Hospital, as well as Encinitas and Oceanside clinics and provides inpatient consultations Robert M. Sheets, MD Conducts pediatric rheumatology clinics on the RCHSD campus and satellite clinics in Murrieta, and Escondido and provides inpatient consultations Provides care for inpatients with Kawasaki disease TEACHING ACTIVITIES Hospital-San Diego, Allergy & Immunology Journal Club which meets weekly. Jane C. Burns, MD Mentors junior faculty in the development of clinical and translational research careers Mentors high school students, undergraduates, medical students, graduate students and postdoctoral fellows in projects on the epidemiology, treatment, and pathophysiology of Kawasaki disease Supervises residents and medical students in the care of Kawasaki disease patients Johanna Chang, MD Teaches UCSD and Scripps rheumatology fellows, UCSD medicine and pediatric Residents, UCSD medical students in rheumatology Developed Pediatric Rheumatology Educational Module in conjunction with 2 medical students and colleague Robert Sheets, an online educational program directed towards 3rd and 4th year medical students Mentor for UCSD Health Sciences International CORE program Presents at monthly resident noon conferences Peter Chira, MD Teaching UCSD medical students in Principles to Practice course. Teaches UCSD residents rotating in outpatient clinics and on inpatient rotations, and provides formal didactic lectures given at noon conference and other teaching conferences. Teaches adult rheumatology fellows from UCSD and Scripps the fundamentals of pediatric rheumatology. Alessandra Franco, MD, PhD Provide basic laboratory instructions for undergraduate students: the Franco s laboratory trains undergrads to perform sterile separation and staining for flow cytometry of immune cells Mentor and thesis advisor for the Master program in Biological Science: Robert Padilla a master student currently mentored in the laboratory has been funded by the NIH with a minority supplement for the translational work of the laboratory. Lecturer on human immune regulation in Immunology course for Biomedical Science Serves on admission committee and as a student advisor for the MD/PhD combined degree program: Medical Students Training Program (MSTP) Bob Geng, MD Mentoring two 3rd year UCSD Pre-Med Undergraduate students: on elements of clinical research as well as topics in allergy and immunology Mentoring a 2nd year UCSD Pediatrics Resident with career advice on fellowship application and for clinical research as well as topics in allergy & Immunology Serving as one of the Faculty Advisors on research for one of the first year Pediatric Endocrinology fellows: interdisciplinary collaboration on examining the relationship between inhaled corticosteroid use and glycemic control Mentoring a 1st year UCSD Adult Allergy & Immunology Fellow in the production of a manuscript on the utility of minor determinants in penicillin allergy testing Mentoring both 1st and 2nd year UCSD Allergy & Immunology Fellows on authoring chapters in Primary Immunodeficiency Medical Education and Urticaria Medical Education Booklets intended for residents and medical students Teaches rotating Fellows, Residents and Medical Students in Allergy & Immunology clinics Received Medical Education Grants from Horizons Pharmaceuticals and the Immune Deficiency Foundation to bring in Visiting Professors to UCSD Hal M. Hoffman, MD Teaches, supervises and mentors allergy/immunology fellows medical students and residents in the pediatric allergy and immunology clinics and in hospital as teaching attending Lectures medical students and graduate students in Immunology and Genetics classes Supervises undergraduate and graduate students and postdoctoral fellows who work in the lab Susan Laubach, MD Supervises and teaches Allergy-Immunology Fellows, Residents in Pediatrics and Internal Medicine, Nurse Practitioner students, and Medical Students. Learners rotate through Primary Immunodeficiency Clinic, Food Allergy Clinic, and general pediatric and adult allergy and immunology clinics and are taught evidence-based diagnosis and treatment of allergic and immunologic disorders Participates in the Speaker s Bureau for Teva Pharmaceuticals, educating primary care physicians, nurse practitioners, physician assistants, and other medical providers about the proper management of asthma and allergic rhinitis Presents lectures to Allergy-Immunology Fellows and faculty at UCSD and Scripps, primarily on the topics of Severe Combined Immunodeficiency and Food Allergy. Conducted several community outreach and education lectures for families of children with food allergy, sponsored by the non-profit Food Allergy Research and Education (FARE) Sydney Leibel, MD Teaches allergy fellows from UCSD and Scripps Clinic Teaches pediatric residents and medical students in allergy and immunology Clinics Lectures at resident conferences Stephanie Leonard, MD Teaches and mentors allergy/immunology fellows Supervises and teaches medical students and residents in the pediatric allergy and immunology clinics and in the hospital as teaching attending Lectures regularly at resident conferences Suhas Radhakrishna, MD Lectures given at Rady Children s Hospital noon conference, professor s rounds, and clinicopathologic conferences, San Diego Regional Emergency Medicine Conference, Hands on Rheumatology Workshop at AAP National Meeting, UCSD School of Medicine courses for second year and fourth year students. Supervises and teaches medical students, residents, and adult rheumatology fellows in pediatric rheumatology clinics Robert M. Sheets, MD Supervises residents with senior resident CPC Teaches Pediatric Residents inpatient and outpatient rheumatology at Rady Children s and in the outpatient clinic several times per week Attends professor rounds for comment on rheumatic diseases. Chisato Shimizu, MD Supervises undergraduate and medical students in the laboratory in projects related to molecular pathogenesis of Kawasaki disease 34 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 35

19 RESEARCH ACTIVITIES In addition to Dr. Burns, Dr. Chisato Shimizu and Dr. Alessandra Franco lead research groups within the Center. Dr. Adriana Tremoulet from the Division of Host-Microbe Systems & Therapeutics serves as Associate Director of the KD Research Program. The Basic Immunology program is led by Dr. Alessandra Franco and specializes in T cell biology, T cell cloning, therapeutic vaccines and glycopeptides. Dr. Franco provides her expertise to numerous collaborators on campus. Seema S. Aceves, MD, PhD NIH funded study (R01) on the mechanisms of tissue remodeling in eosinophilic esophagitis (EoE) (the role of pro-inflammatory and pro-fibrotic molecules), diagnosis (biomarker discovery), and treatment options and their effects on disease complications such as esophageal remodeling Research on novel agents to alter esophageal remodeling Studies of the role of novel cells such as innate lymphocytes in EoE pathogenesis Site Principal Investigator, Consortium for Eosinophilic Gastrointestinal Researchers (CEGIRS), an NIH funded multicenter consortium Program Leader, Pilot Projects, CEGIRS Executive Council member, The International Gastrointestinal Eosinophil Research network Editorial Board of Journal of Allergy and Clinical Immunology Lori Broderick, MD, PhD Diseases involving extremes of immune dysregulation including primaryimmunodeficiencies and autoinflammatory syndromes with a goal of identifying novel genetic and molecular mechanisms NIH funded study (K08) on the genetics and immunoregulatory mechanisms of Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome Arthritis National Research Fund to support evaluation and characterization of novel immunodeficiency with dysmorphic features. Jane C. Burns, MD The pathophysiology, immunology, diagnosis, etiology, treatment, genetics, epidemiology and history of Kawasaki disease A two-center Phase I/IIa trial of atorvastatin for primary treatment of Kawasaki disease patients with early coronary artery abnormalities A two-center Phase I/IIa trial of anakinra for primary treatment of Kawasaki disease patients with early coronary artery abnormalities Longitudinal study of adolescents and young adults with a history of Kawasaki disease in childhood Johanna Chang, MD Pediatric musculoskeletal ultrasound Principle site investigator of CARRA Registry multicenter observational study of pediatric rheumatologic disease Principle site investigator of STOP-JIA multicenter observational study looking at outcomes of 3 consensus treatment plans for polyarticular JIA Peter Chira, MD Co-investigator for a number of CARRA (Childhood Arthritis and Rheumatology Research Alliance) studies. Site investigator for Industry-sponsored Clinical Trials (Pfizer, Janssen). Transition of youth with special health care needs, with emphasis on patients with pediatric rheumatic diseases. Alessandra M. Franco, MD, PhD Human basic and translational immunology with a specific interest in T cell biology studying T cell differentiation and functions ex vivo in T cell-mediated human diseases T cell recognition for vaccine development and immunotherapy Human T cell cloning from peripheral blood and inflammatory infiltrates in Tissues Designer glycopeptides containing pan-carcinoma TACA Tn tailored to bind with high affinity multiple HLA class I alleles (super-types) to treat a large population by expanding in vivo CD8+ cytotoxic T cells that recognize the TACA antigen Established reliable techniques for the secondary end-points in Clinical trials by tracking innate and adaptive immune cells before and after therapy in KD patients Collaborates with PIs at UCSD to validate in vivo murine models with in vitro human studies Bob Geng, MD Primary Site Investigator for two Phase III Clinical Trials on the use of 16% Subcutaneous Immunoglobulin replacement therapies for Primary Immunodeficiency Syndromes Primary Site Investigator for Clinical Trials on the use of Mepolizumab (anti-il5 monoclonal antibody) for the treatment of severe persistent asthma in 6-12 year olds (Phase IIb) and in patients 12 and above (Phase IIIb/IV) Primary Site Investigator for Phase III Clinical Trial on the use of novel oral CRTH2 antagonist for moderate to severe persistent asthmatics above 12 years of age Primary Investigator for retrospective study of outpatient Penicillin Allergy SkinTesting at Rady s Allergy & Immunology specialty clinic over the past 5 years toidentify sensitivity and specificity of current skin testing procedure Primary Investigator for retrospective study on the comparison between intravenous immunoglobulin replacement and subcutaneous immunoglobulin replacement for primary immunodeficiency patients. Member and Investigator of the UCSD Airway Disease Research Center (ADRC) Hal M. Hoffman, MD Role of innate immunity and targeted therapy of autoinflammatory disorders in collaboration with international investigators and industry Characterization of NLRP3 inflammasome function and its role in numerous human diseases using a number of experimental models, in cluding in vitro cell lines, ex vivo monocytes and genetically modified mice in collaboration with a variety of UCSD investigators within and outside of the department Genetic basis of rare inherited disorders including rare urticarial, immunodeficiency, and autoinflammatory disorders Sydney Leibel, MD University of Waterloo Seed Grant looking at Perspectives of Children with Food Allergies Interests in Social Determinants of Health and role in atopic diseases including food allergies and asthma Stephanie Leonard, MD Site Principle Investigator for clinical trials investigating oral and epicutaneous immunotherapy for peanut and milk allergies in children. Established the San Diego Food Allergy Registry to collect epidemiologic,laboratory and genetic data that will allow for investigations into factors affecting the development and natural history of food allergy. Conducting clinical research to investigate cross-reactivity among fish species and evaluate if fish-allergic patients may be able to tolerate certain fish species while avoiding others. Suhas Radhakrishna, MD Co-investigator on PRCSG clinical trials and CARRA registry Interest in genetic basis of familial autoimmune and auto-inflammatory disorders Robert M. Sheets, MD Clinical trials of new treatments for pediatric rheumatologic diseases as part of the Pediatric Rheumatology group Randomized clinical trial of cyclosporine versus low-dose meth- 36 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 37

20 otrexate for Infants <8 mos. with Kawasaki disease and coronary artery abnormalities Chisato Shimizu, MD Genetics, genomics, and molecular pathogenesis of Kawasaki disease Seema S. Aceves, MD, PhD Director of the pediatric allergy, immunology, rheumatology specialty rotation (for allergy/immunology fellows from UCSD and Scripps Clinic, and pediatric residents from UCSD) Teaches UCSD and Scripps allergy fellows, UCSD medicine and pediatric residents in allergy, EGID clinics three half-days per week Mentors UCSD undergraduate, medical students, and residents in laboratory studies on eosinophilic esophagitis GRANTS Seema S. Aceves MD, PhD 1 R01 AI (PI) 07/01/ /30/2016 $250,000 NIH (NIAID) Mechanisms leading to tissue damage in chronic allergic eosinophilic esophagitis W81XWH /DA 09/01/ /30/2014 $299,839 TGF-beta Gene Polymorphisms in Food Allergic vs. Non-Food Allergic Eosinophilic Esophagitis AAAAI/APFED $140,000 HOPE Pilot Project in Eosinophilic Diseases 1U54AI /15/ /31/2019 $73,739 (Site PI, UCSD/RCHSD NIH/NIAID/NIDDH/NCATS Consortium of Eosinophilic Gastrointestinal Disease Researchers Pilot Project. National consortium for the study of eosinophilic gastrointestinal Disorders /24/ /23/2016 $145,091 Raptor Pharmaceuticals (Co-PI) Role of cysteamine in decreasing fibrosis in eosinophilic esophagitis CR-15 RCHSD 07/01/ /30/2016 $50,000 Academic Enrichment (PI) L-9 and ILC2s in pediatric eosinophilic esophagitis Lori Broderick, MD, PhD A.P. Giannini Foundation Post-Doctoral Research Fellowship 07/ /2014 $46,000 Genetics of Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis syndrome Arthritis National Research Foundation 06/ /2016 $100,000 B cells in immune dysregulation 1K08HD A1 05/ /2019 $693,495 NIH/NICHD Molecular Genetic and Immunoregulatory Mechanisms in PFAPA Syndrome Jane C. Burns, MD Macklin Foundation Challenge Grant (PI) 07/1/ /30/2020 Comprehensive funding for KD research that spans three topics: biomarker discovery and validation, etiology of KD, and immunology of KD 1R01HD A1 (Co-PI) 09/23/ /30/2018 NICHD Phase I/IIa trial of atorvastatin for children with acute Kawasaki disease U54HL (PI) 06/01/ /31/2016 idash: Integrating Data for Anaylsis, Anonymization and Sharing" KD Foundation, (PI) 01/01/ /31/2016 Biomarker Discovery for Kawasaki disease" Rady Children s Hospital 07/01/ /30/2015 Foundation (Co-PI) Developing biomarkers for Kawasaki disease" Peter Chira, MD CNTO148JIA3003 (PI) 05/01/ A Multicenter Open Label Trial of Intravenous Golimumab, a Human TNFα Antibody, in Pediatric Subjects with Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy A Pfizer Pharmaceuticals (PI) 06/01/ Efficacy, Safety and Tolerability of Tofacitinib for Treatment of Polyarticular Course Juvenile Idiopathic Arthritis (JIA) in Children and Adolescent Subjects Rady Academic Enrichment Funds (PI) 07/01/ /30/2016 Establishing a pediatric rheumatology center of excellence: Development of the clinical research program Alessandra Franco, MD, PhD R01 HL (PI) 06/01/ /28/2015 "Impact of TNFa blockade on immune function in acute Kawasaki disease" 15 GRNT (PI) 01/01/ /31/2016 Role of Atorvastatin in preventing arterial damage in Kawasaki disease by inducing immune-regulation KD Foundation (Co-PI) 01/01/ /31/2015 Biomarker Discovery for Kawasaki disease RO1 HD (Co-PI) 09/23/ /30/2018 Phase I and IIa trial of atorvastatin in children with acute Kawasaki disease Rady Children s Foundation (Co_PI) 07/01/ /30/2020 Challenge Grant- Kawasaki Disease Research Hal M. Hoffman, MD UCSD/RCHSD Intramural Grant for Genomics Research 3/01/12 02/28/14 "UCSD Pediatrics- Genetic Basis of Hoffman Syndrome" R01 HL (Co-I) 5/15/15 3/31/19 NIH/NHLBI "Transcriptional Control of Lung Macrophage Development " NIH/NIAMS Role (Co-I) 9/23/14 8/31/15 "Development of a TAK1 Inhibitor for NOMID" P01 CA A1 9/19/14-8/31/19 "Innate Immune Responses and Vaccines Against Tumor-Associated Herpesviruses" R01 HL (Role Co-I) 9/1/14 8/29/19 NIH/NCI "FGF-10 Expression in a Fetal Mouse Lung Model of Bronchopulmonary Dysplasia" R01 AR /1/13 8/31/18 NIH/NHLBI Role Co-I (PI - Prince) "Inflammasome Regulation of Bone Resorption" R01 AI (Co-I) 6/1/13 5/31/18 NIH/NIAID Chromosome 17q, allergic information, and remodeling PUBLICATIONS Aceves SS. Eosinophilic esophagitis. Immunology and allergy clinics of NorthAmerica. 2015; 35(1): PubMed [journal] PMID: Aceves SS. Food allergy testing in eosinophilic esophagitis: what the gastroenterologist needs to know. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2014; 12(8): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Aceves SS. Food and aeroallergens in eosinophilic esophagitis: role of the allergist in patient management. Current opinion in gastroenterology. 2014; 30(4): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Aceves SS. Remodeling and fibrosis in chronic eosinophil inflammation. Digestive diseases (Basel, Switzerland). 2014; 32(1-2): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Aceves SS. Unmet therapeutic needs in eosinophilic esophagitis. Digestive diseases (Basel, Switzerland). 2014; 32(1-2): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Beppu LY, Anilkumar AA, Newbury RO, Dohil R, Broide DH, Aceves SS. TGFβ1-induced phospholamban expression alters esophageal smooth muscle contraction in patients with eosinophilic esophagitis. J Allergy Clin Immunol PMID: Beppu, L, Yang T, Luk M, Newbury RO, Palmquist J, Dohil R, Kurten R, Broide DH, Aceves SS. MMPs-2 and -14 are elevated in eosinophilic esophagitis and reduced following topical corticosteroid therapy. Journal of Pediatric Gastroenterol Hepatology. 61(2): Bertin S, Aoki-Nonaka Y, De Jong PR, Nohara LL, Xu H, Stanwood SR, Sriklanth S, To K, Abramson L, Touma R, Yu T, Han T, Li X, González-Navajas JM, Herdman S, Corr M, Fu G, Gwack Y, Franco, A., Jefferies WA and Raz E TRPV1 channel regulates CD4 + T cells activation and proinflammatory properties. Nature Immunology. 15: Research article. Blinder M, Geng B, Lisker-Melman M, Korenblat K, Crippin J, Chapman W, Shenoy S, Field J. Successful Orthotopic Liver Transplantation in an Adult Patient with Sickle Cell Disease and Review of the Literature. Hematology Reports 2013 Vol 5: E1 Broderick, L., Gandhi, C., Mueller, J.L., Putnam, C.D., Shayan, K., Peterson, K.S., Aceves, S.S., Sheets, R.M., Peterson, B.M., Newbury, R.O., Giclas, P.C., Hoffman, H.M., and J.F. Bastian. Complement Factor I Deficiency Presenting as Acute Hemorrhagic Leukoencephalitis. J Clin Immunol. 2013; 311: Broderick L, Gandhi C, Mueller JL, Putnam CD, Shayan K, Giclas PC, Peterson KS, Aceves SS, Sheets RM, Peterson BM, Newbury RO, Hoffman HM, Bastian JF. Mutations of complement factor I and potential mechanisms of neuroinflammation in acute hemorrhagic leukoencephalitis. J Clin Immunol, 33(1):162-71, Broderick L., Kastner D.L., and H.M. Hoffman. Recurrent Fever Syndromes. In: Primary Immunodeficiency Diseases: a Molecular and Genetic Approach, 3rd ed. H.D. Ochs, C.I.E Smith and J.M. Puck, eds. Oxford University Press, New York, NY Broderick, L. and H.M. Hoffman. cascading Specks. Nat Immunol. 2014;15(8): Broderick L, De Nardo D, Franklin BS, Hoffman HM, Latz E. The Inflammasome and Autoinflammatory Syndromes. Annu Rev Pathol. 2015; 10: 395. PMID: Brydges, S.D.,* Broderick, L.,* McGeough, M.D., Pena, C.A., Mueller, J.L., Hoffman, H.M. Divergence of IL-1, IL-18 and cell death in NLRP3 inflammasomopathies. J Clin Invest (11): (* denotes shared first authorship) Burns, J.C., Song, Y., Bujold, M., Shimizu, C., J.T. Kanegaye, Tremoulet, A.H., Franco, A Immune- monitoring in Kawasaki disease children treated with infliximab and intravenous immunoglobulin. Clinical Experimental Immunology, 174: Research article. Burns JC, Herzog L, Fabri O, Tremoulet AH, Rodo X, Uehara R, Burgner D, Bainto E Pierce D, Tyree M, Cayan D for the Kawasaki Disease Global Climate Consortium. Seasonality of Kawasaki disease: A global perspective. PLoS One 2013 Sep 18;8(9):e doi: /journal.pone (PMID: ) Burns JC, Song Y, Bujold M, Shimizu C, Kanegaye JT, Tremoulet AH, Franco A. Immune-monitoring in Kawasaki disease patients treated with infliximab and intravenous immunoglobulin. Clinical and Experimental Immunology. 2013;174: (PMID: ) Burns JC, Touma R, Song Y, Padilla RL, Tremoulet AH, Sidney J, Sette A, Franco A. Fine specificities of natural regulatory T cells after IVIG therapy in patients with Kawasaki disease. Autoimmunity Mar 30:1-8. (PMID: ) Chang CJ, Kuo HC, Chang JS, Lee JK, Tsai FJ, Khor CC, Chang LC, Chen SP, Ko TM, Liu YM, Chen YJ, Hong YM, Jang GY, Hibberd ML, Kuijpers T, Burgner D, Levin M, Burns JC, Davila S, Chen YT, Chen CH, Wu JY, Lee YC and the International Kawasaki Disease Genetics Consortium, Korean Kawasaki Disease Genetics Consortium, Taiwan Kawasaki Disease Genetics Consortium. Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility. PLoS One Aug 30;8(8):e doi: /journal.pone (PMID: ) Chang JC, Burns A. Role of musculoskeletal ultrasound in juvenile arthritis. International Journal of Clinical Rheumatology, 2013: p Chang JC, Radhakrishna S, Sheets, R. Arthritis. Orthopedic Knowledge Update: Pediatrics 5. Chapter submitted and accepted, not yet published. Chira, P. Dr. Chira Replies. Journal of Rheumatology 2015 May;42(5):903. PMID: Chehade M, Aceves SS, Furuta GT, Fleischer DM. Food allergy and eosinophilic esophagitis: what do we do? The journal of allergy and clinical immunology. In practice. 2015; 3(1): PubMed [journal] PMID: Cho JY, Doshi A, Rosenthal P, Beppu A, Miller M, Aceves SS. Smad3-deficient mice have reduced esophageal fibrosis and 38 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 39

21 angiogenesis in a model of egg-induced eosinophilic esophagitis. Journal of pediatric gastroenterology and nutrition. 2014; 59(1):10-6. NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Cho JY, Rosenthal P, Miller M, Pham A, Aceves SS, et al. Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis. International immunopharmacology. 2014; 18(1): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Clark, D and Chira, P*. Back Pain. 5 Minute Pediatric Consult, 7th Edition. Wolters Kluwer Health - Lippincott Williams & Wilkins. (June 2015) Doherty TA, Baum R, Newbury RO, Yang T, Dohil R, Aceves SS. Group 2 innate lymphocytes (ILC2) are enriched in active eosinophilic esophagitis. The Journal of allergy and clinical immunology. 2015; 136(3): e3. NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Franco A, Tuoma R, Song Y, Shimizu C, Tremoulet AH, Kanegaye J, Burns JC. Specificity of regulatory T cells that modulate vascular inflammation. Autoimmunity. 2014;47(2): (PMID: ) Geng B. Mastocytosis. In: Joo SS, Kau A (eds). The Washington Manual: Allergy, Asthma, and Immunology Subspecialty Consult. Second Edition. Philadelphia, PA: Lippincott Williams & Wilkins. 2013; pg Geng B. Conditions associated with Eosinophilia. In: Joo SS, Kau A (eds). The Washington Manual Allergy, Asthma and Immunology Subspecialty Consult. Second Edition. Philadelphia, PA: Lippincott Williams & Wilkins. 2013; pg Geng B, Thakor A, Clayton E, Finkas L, Riedl MA. Factors associated with negative histamine control for penicillin allergy skin testing in the inpatient setting. Annals Allergy Asthma Immunology 2015, Jul;115(1):33-8 Gordon CT, Jiminez-Fernandez, Daniels LB, Kahn A, Shimizu C, Burns JC, Gordon JB. Management and outcome of pregnancy in women with a history of Kawasaki disease. Brit J Obs Gyn Mar 6. doi: / [Epub ahead of print](pmid: ) Greenhawt M, Aceves SS, Spergel JM, Rothenberg ME. The management of eosinophilic esophagitis. The journal of allergy and clinical immunology. In practice. 2013; 1(4):332-40; quiz PubMed [journal] PMID: Hirano I, Aceves SS. Clinical implications and pathogenesis of esophageal remodeling in eosinophilic esophagitis. Gastroenterology clinics of North America. 2014; 43(2): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Hoang LT, Shimizu C, Ling L, Naim A, Khor CC, Tremoulet AH, Kanegaye JT, Hibberd ML, Burns JC. Global gene expression profiling identifies new therapeutic targets in acute KD. Genome Medicine. 2014, 6:541. DOI: /s Kanegaye JT, Van Cott E, Tremoulet AH, Salgado A, Shimizu C, Kruk P, Hauschildt J, Sun X, Jain S, Burns JC. Lymph-node-first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr, 162(6): , 1263.e1-2, Klinnert MD, Silveira L, Harris R, Moore W, Atkins D, Aceves SS. Health-related quality of life over time in children with eosinophilic esophagitis and their families. Journal of pediatric gastroenterology and nutrition. 2014; 59(3): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Krakowski AC, Kim SS, Burns JC. Transient lingual papillitis associated with confirmed herpes simplex virus 1 in a patient with Kawasaki disease. Pediatr Dermatol Nov-Dec;31(6):e (PMID: ) Kung E, Kahn AM, Burns JC, Marsden A. In vitro validation of patient-specific hemodynamic simulations in coronary aneurysms caused by Kawasaki disease. Cardiovasc Eng Technol Jun 1;5(2): (PMID: ) Kurabi A, Lee J, Wong C, Pak K, Hoffman HM, Ryan AF, Wasserman SI. The inflammasome adaptor ASC contributes to multiple innate immune processes in the resolution of otitis media. Innate Immun Feb;21(2): PMID: Lee A, Shimizu C, Oharaseki T, Takahashi K, Daniels LB, Adamson R, Dembitsky W, Gordon JB, Burns JC. Role of TGFβ signaling in remodeling of non-coronary artery aneurysms in Kawasaki disease. Pediatr Dev Pathol Jul-Aug;18(4): doi: / OA.1. Epub 2015 Apr 9. (PMID: ) Leonard SA, Caubet JC, Kim JS, Groetch M, Nowak-Wegrzyn A. Baked milk- and egg-containing diet in the management of milk and egg allergy. J Allergy Clin Immunol Pract. 2015;3(1): Leonard SA, Nowak-Wegrzyn A. Manifestations, Diagnosis, and Management of Food Protein Induced Enterocolitis Syndrome. Pediatr Ann. 2013;42(7): Leuin SC, Shanbhag S, Lago D, Sato Y, Sun X, Jain S, Burns JC, Tremoulet AH. Hoarseness as a presenting symptom in children with Kawasaki disease. Ped Inf Dis J. 2013;32(12): (PMID: ) Lia Z, Chaoa TC, Changa K-Y, Lina N, Patila VS, Shimizu C, Head SR, Burns JC, Rana TM. The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnrnpl. PNAS Jan 21;111(3): (PMID: ) Lieberman Pl, Hoffman HM. Possible cold autoinflammatory syndrome. J Allergy Clin Immunol Pract Sep-Oct;2(5):642. PMID: Lin AE, Beasley FC, Keller N, Hollands A, Urbano R, Troemel ER, Hoffman HM, Nizet V. A group A Streptococcus ADPribosyltransferase toxin stimulates a protective interleukin 1β-dependent macrophage immune response. MBio Mar 10;6(2):e00133 PMID: Lin J, Liu V, Sato YZ, Jiminez-Fernandez S, Pourfarzib R, Winegar DA, Tremoulet AH, Gordon JB, Daniels LB, Burns JC. Lipoprotein particle concentrations in children and adults following Kawasaki disease. J Pediatr Oct;165(4): (PMID: ) Ling XB, Kanegaye JT, Ji J, Peng S, Sato Y, Tremoulet A, Burns JC, Cohen HJ. Point-of-care differentiation of Kawasaki disease from other febrile illnesses. J Pediatr, 162(1): e3, Mak RH, Hoffman HM, Transplantation: Outcomes of prenatal immunosuppression. Nat Rev Nephrol Jul;11(7): PMID: Middleton's Allergy, Berin MC, Furuta GT, Aceves SS. Eighth ed. Adkinson JNBochner BSBurks WBusse WWHolgate ST, editors. Philadelphia: Saunders; Chapter 67, Gastrointestinal Mucosal Immunology; p p. Miller M, Rosenthal P, Beppu A, Mueller JL, Hoffman HM, Tam AB, Doherty TA, McGeough MD, Pena CA, Suzukawa M, Niwa M, Broide DH. ORMDL3 transgenic mice have increased airway remodeling and airway responsiveness characteristic of asthma. J Immunol Apr 15;192(8): PMID: ; PMCID: PMC Numano F, Shimizu C, Jiminez-Fernandez S, Vejar M, Salgado A, Tremoulet AH, Gordon JB, Burns JC, Daniels LB. Galectin-3 as a predictor of myocardial fibrosis in Kawasaki Disease Dec 15;201: doi: /j.ijcard Epub 2015 Jul 27. (PMID: ) Ogata S, Shimizu C, Franco A, Touma R, Kanegaye JT, Choudhury BP, Naidu NN, Kanda Y, Hoang YT, Hibberd ML, Tremoulet AH, Varik A, Burns JC. Treatment responses in Kawasaki disease are associated with sialylation levels of endogenous but not therapeutic intravenous Immunoglobulin G. PLoS ONE.2013;8(12):e (PMID: ) Ogata S, Tremoulet AH, Sato Y, Ueda K, Shimizu C, Sun X, Jain S, Silverstein L, Baker AL, Tanaka N, Ogihara Y, Ikehara S, Takatsuki S, Sakamoto N, Kobayashi T, Fuse S, Matsubara T, Ishii M, Saji T, Newburger JW, Burns JC. Coronary artery outcomes among children with Kawasaki disease in the United States and Japan. Int J Cardiol Oct 9;168(4): (PMID: ) Ohno-Machado L, Agha Z, Bell DS, Dahm L, Day ME, Doctor JN, Gabriel D, Kahlon MK, Kim KK, Hogarth M, Matheny ME, Meeker D, Nebeker JR; the pscanner team. pscanner: patient-centered Scalable National Network for Effectiveness Research. J Am Med Inform Assoc Apr 29. doi: /amiajnl (PMID: ) Otani IM, Anilkumar AA, Newbury RO, Bhagat M, Beppu LY, Dohil R, Broide DH, Aceves SS. Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol, 131(6): , Otani IM, Anilkumar AA, Newbury RO, Bhagat M, Beppu LY, Dohil R, Broide DH, Aceves SS. Anti-IL-5 therapy reduces mast cells and IL-9 cells in pediatric eosinophilic esophagitis. In 131(6): PMID: Padler-Karavani V, Tremoulet AH, Yu H, Chen X, Burns JC, Varki A. A Simple Method For Assessment Of Human Anti- Neu5Gc Antibodies Applied to Kawasaki Disease. PLoS One. 2013;8(3):e (PMID: ) Park, T; Chira, P (co-1st author); Miller, K; and Nugent, L. Living Profiles: An example of user-centered design in developing a teen-oriented personal health record. Personal and Ubiquitous Computing. 19, 1 (January 2015), DOI= /s Qu C, Bonar SL, Hickman-Brecks CL, Abu-Amer S, McGeough MD, Peña CA, Broderick L, Yang C, Grimston SK, Kading J, Abu-Amer Y, Novack DV, Hoffman HM, Civitelli R, Mbalaviele G. NLRP3 mediates osteolysis through inflammation-dependent and -independent mechanisms. FASEB J Dec 4; PMID: Rajan J, Laubach S, Best Articles Relevant to Pediatric Allergy and Immunology: Review of Fish Consumption in Infancy and Asthma- Like Symptoms at Preschool Age, Pediatrics 2013; 132:S10-S11. Rajan J, Laubach S, Best Articles Relevant to Pediatric Allergy and Immunology: Review of Child and Parental Reports of Bullying in a Consecutive Sample of Children With Food Allergy, Pediatrics 2013; 132:S23-S24. Rawson R, Anilkumar A, Newbury RO, Bafna V, Aquino M, Palmquist J, Hoffman HM, Mueller J, Dohil R, Broide DH, Aceves SS. The TGFb1 promoter SNP C-509T and food sensitization promote esophageal remodeling in pediatric eosinophilic esophagitis. PLoS One. 10(12):e Rodó X, Curcoll R, Robinson M, Ballester J, Burns JC, Cayan DR, Lipkin WI, Williams BL, Couto-Rodriguez M, Nakamura Y, Uehara R, Tanimoto H, Morguí JA. Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan. Proc Natl Acad Sci U S A. 2014;111(22): doi: /pnas (PMID: ) Salo E, Griffiths EP, Farstad T, Schiller B, Nakamura Y, Yashiro M, Uehara R,Best BM, Burns JC. Incidence of Kawasaki disease in northern European countries. Pediatr Int, 54(6):770-2, Sampson HA, Aceves SS, Bock SA, James J, Jones S, et al. Food allergy: a practice parameter update The Journal of allergy and clinical immunology. 2014; 134(5): e43. PubMed [journal] PMID: Sato YZ, Molkara DP, Daniels LB, Tremoulet AH, Shimizu C, Kanegaye JT, Best BM, Snider JV, Frazer JR, Maisel A, Burns JC. Cardiovascular biomarkers in acute Kawasaki disease. Int J Cardiol, 20;164(1):58-63, Sengupta D, Kahn AM, Shirinsky O, Burns JC, Marsden AL. Thrombotic risk stratification using computational modeling in patients with coronary artery aneurysms following Kawasaki disease. Biomech Model Mechanobiol Apr 11. [Epub ahead of print] (PMID: ) Scott DR, Chan S, Chang J, Broderick L, Hoffman HM. Recurrent fevers and failure to thrive in an infant. Allergy Asthma Proc, 34(5):473-9, Scott D, Laubach S, Best Articles Relevant to Pediatric Allergy and Immunology: Review of Loss-of-Function Mutations in the IL- 21 Receptor Gene Cause a Primary Immunodeficiency Syndrome, Pediatrics 2013; 132:S52. Scott D, Laubach S, Best Articles Relevant to Pediatric Allergy and Immunology: Review of Age and Risks of FDA-Approved Long- Acting b2-adrenergic Receptor Agonists, Pediatrics 2013;130;S41. Schoepfer AM, Panczak R, Zwahlen M, Kuehni CE, Coslovsky M, Aceves SS. How do gastroenterologists assess overall activity of eosinophilic esophagitis in adult patients? The American journal of gastroenterology. 2015; 110(3): PubMed [journal] PMID: Schoepfer AM, Straumann A, Panczak R, Coslovsky M, Kuehni CE, Aceves SS. Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis. Gastroenterology. 2014; 147(6): e21. NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Shimizu C, Sood A, Lau HD, Oharaseki T, Takahashi K, Krous, HF, Campman S, Burns JC. Cardiovascular pathology in two young adults with sudden death attributed to Kawasaki Disease in childhood. Cardiovasc Pathol Feb 24. pii: S (15) [Epub ahead of print] (PMID: ) Shimizu C, Kim J, Stepanowsky P, Trinh C, Lau HD, Akers JC, Chen C, Kanegaye JT, Tremoulet A, Ohno-Machado L, Burns JC. Differential expression of mir-145 in children with Kawasaki disease. PLoS One, 8(3):e58159, Shimizu C, Oharaseki T, Takahashi K, Kottek A, Franco A, Burns JC. The role of TGF-β and myofibroblasts in the arteritis of Kawasaki 40 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 41

22 disease. Hum Pathol. 44(2):189-98, Shimizu C, Kim J, Stepanowsky P, Trinh C, Lau HD, Arker J, Chen C, Kanegaye JT, Tremoulet AH, Ohno-Machado L, Burns JC. Differential expression of micrornas in children with Kawasaki disease. PLoS One 2013;8(3):e (PMID: ) Sleiman PM, Wang ML, Cianferoni A, Aceves SS, Gonsalves N,. GWAS identifies four novel eosinophilic esophagitis loci. Nature communications. 2014; 5:5593. NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Stouch AN, Zaynagetdinov R, Barham WJ, Stinnett AM, Slaughter JC, Yull FE, Hoffman HM, Blackwell TS, Prince LS. IκB kinase activity drives fetal lung macrophage maturation along a non-m1/ M2 paradigm. J Immunol Aug 1;193(3): PMID: ; PMCID: PMC Ta V, Laubach S. Best Articles Relevant to Pediatric Allergy and Immunology: Review of Introduction of complementary foods and the relationship to food allergy. Pediatrics Nov;134 Suppl 3:S Ta V, Laubach S. Best Articles Relevant to Pediatric Allergy and Immunology: Review of Probiotic administration in early life, atopy, and asthma: a meta-analysis of clinical trials. Pediatrics Nov;134 Suppl 3:S141. Ta V, Laubach S. Best Articles Relevant to Pediatric Allergy and Immunology: Review of Introduction of complementary foods and the relationship to food allergy. Pediatrics Nov;134 Suppl 3:S Ta V, Laubach S. Best Articles Relevant to Pediatric Allergy and Immunology: Review of Probiotic administration in early life, atopy, and asthma: a meta-analysis of clinical trials. Pediatrics Nov;134 Suppl 3:S141. Ta V, Tsang RT, Mannino Avila E, Leonard SA. Delay in diagnosis of severe food protein-induced enterocolitis syndrome caused by mango. Ann Allergy Asthma Immunol. 2015;115(2): Thakor T, Geng B, Liebhaber M, Moore T, Wang K, Roberts RL. Successful Stem Cell Transplantation in Chediak-Higashi Syndrome (CHS). Journal of Allergy & Clinical Immunology- In Practice; 2015 Mar-Apr; 3(2): Tkachenko E, Rawson R, La E, Doherty TA, Baum R, Aceves SS. Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression. The Journal of allergy and clinical immunology. 2015; PubMed [journal] PMID: Tilson H, Primatesta P, Kim D, Rauer B, Hawkins PN, Hoffman HM, Kuemmerle-Deschner J, van der Poll T, Walker UA. Methodological challenges in monitoring new treatments for rare diseases: lessons from the cryopyrin-associated periodic syndrome registry. Orphanet J Rare Dis Sep 10;8:139. PMID: ; PMCID: PMC Toldo S, Mezzaroma E, McGeough MD, Peña CA, Marchetti C, Sonnino C, Van Tassell BW, Salloum FN, Voelkel NF, Hoffman HM, Abbate A. Independent roles of the priming and the triggering of the NLRP3 inflammasome in the heart. Cardiovasc Res Feb 1;105(2): PMID: Tremoulet AH, Jain S, Jaggi P, Jiminez-Fernandez S, Pancheri JM, Sun X, Kanegaye JT, Kovalchin JP, Printz B, Ramilo O, Burns JC. Phase III randomized, double-blind, placebo-controlled trial of infliximab for intensification of primary therapy for Kawasaki disease. Lancet May 17;383(9930): (PMID: ) Tremoulet AH, Dutkowski J, Jin B, Jain S, Sun X, Kanegaye JT, SatoY, Ji J, Ling XB, Cohen H, Burns JC. Novel data-mining approach identifies biomarkers for diagnosis of Kawasaki disease. Pediatr Res.2015 Nov;78(5): doi: /pr Epub 2015 Aug 3.(PMID: ) Wang YT, Geng B, Yoo KY, Stiehm ER, Garcia-Lloret M, Wong D, Smart C, Worswick S, Barnhill RL. Cutaneous Granulomas and Epidermodysplasia Verruciformis in Early Onset Combined Immunodeficiency Syndrome. Am J Dermatopathol Feb;36(2): Wen T, Dellon ES, Moawad FJ, Furuta GT, Aceves SS. Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation. The Journal of allergy and clinical immunology. 2015; 135(1): NIHMSID: NIHMS PubMed [journal] PMID: , PMCID: PMC Wree A., Broderick L., Canbay A., Hoffman H.M., Feldstein, A.E. From NAFLD to NASH to cirrhosis new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol (11): Wree A, McGeough MD, Peña CA, Schlattjan M, Li H, Inzaugarat ME, Messer K, Canbay A, Hoffman HM, Feldstein AE. NLRP3 inflammasome activation is required for fibrosis development in NAFLD. J Mol Med (Berl) Oct;92(10): PMID: Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, Hoffman HM, Feldstein AE. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology Mar;59(3): PMID: ; PMCID: PMC Yao Y, Vent-Schmidt J, McGeough MD, Wong M, Hoffman HM, Steiner TS, Levings MK., Tr1 Cells, but Not Foxp3+ Regulatory T Cells, Suppress NLRP3 Inflammasome Activation via an IL-10- Dependent Mechanism. J Immunol Jul 15;195(2): PMID: Yu, J., Murakami, T., Nagasu, H., Hoang, H., Broderick, L., Hoffman, H.M., Horng, T. Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy. Proc. Natl. Acad. Sci. U.S.A Proc Natl Acad Sci U S A Oct 28;111(43): AWARDS Seema S. Aceves MD, PhD Reviewer, NIH Study Section Permanent Member 2012-current Elected to the American Society of Clinical Investigation, 2013 Voted among Best Doctors by SDCMA 2013, 2014 Lori Broderick, MD, PhD American Academy of Allergy, Asthma and Immunology Travel Grant Recipient, 2013 A.P.Giannini Post-doctoral Research Fellowship, Arthritis National Research Foundation Scholar, Jane C. Burns, MD Member, AHA Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease Peter Chira, MD Member, Childhood Arthritis and Rheumatology Research Alliance Finance and Marketing Committee Member, Childhood Arthritis and Rheumatology Research Alliance (CARRA) Pediatric Clinical and Therapeutics, Abstract Reviewer, ACR/ARHP 2015 Annual Scientific Meeting, July 2015 Journal Reviewer, Ad hoc, Pediatric Rheumatology Journal, June 2015 Journal Reviewer, Ad hoc, Arthritis Care and Research, November 2014 Bob Geng, MD Editorial Board for the patient focused magazine IG-Living for primary immunodeficiency Hal M. Hoffman, MD Member, American Society of Clinical Investigation Member, Society of Pediatric Research Susan S. Laubach, MD American Academy (AAP) California Chapter 3 Champion of the Program Medical Home Chapter Champions Program on Asthma, Allergy, and Anaphylaxis (MHCCPAAA). Stephanie Leonard, MD Academic Enrichment Fund Program Grant, Rady Children s Hospital, 2014 UCSD National Center of Leadership in Academic Medicine, class member, 2015 Medical Advisory Board, Food Allergy Research & Education (FARE), 2015-present Robert Sheets, MD : UCSD Pediatric Residency Teacher of the year award. 42 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 43

23 Critical Care & Anesthesia 44 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 45

24 INTRODUCTION FACULTY The Division of Critical Care is responsible for the Pediatric Intensive Care Unit (PICU) at Rady Children s Hospital- San Diego (RCHSD), a 24-bed unit that admits approximately 1,200 patients per year. The PICU multidisciplinary team is led by one of eight attending pediatric critical care physicians. This team is responsible for the care of all patients in the intensive care unit, working closely with physicians from other specialty and subspecialty disciplines to assure excellent care. The PICU and its staff are an essential component of many programs at RCHSD, including the Regional Pediatric Trauma Center and the pediatric transport program. Dr. Susan Duthie is the Medical Director of the PICU and Sandeep Khanna is the Clinical Director. The Division of Anesthesia provides anesthesia services for 22,500 inpatient and outpatient procedures per year. The operating rooms consistently score in the top five percent of children s hospitals in operating room efficiency and utilization, as well as on-time starts. This has been achieved through the creative scheduling of Dr. Alvin Faierman, Director of Perioperative Scheduling, and via collaboration with Dr. Andy Zimmerman, Chief of Anesthesia (Note: Previous Chief of Anesthesia was Clay Stanley, MD). Acute Pain Service is headed by Dr. George Ulma, and provides services to approximately 2,500 patients annually. Susan Duthie, MD, FAAP Medical Director, Critical Care Section Bradley Peterson, MD, FAAP, FCCM, Associate Clinical Professor and Anesthesiology Sandeep Khanna, MD, FAAP Assistant Clinical Professor of Anesthesiology/ Critical Care Helen Harvey, MD Critical Care Raveen Raviendran, MD Critical Care DIVISION FAST FACTS PICU admits over 1,200 patients per year Provide Anesthesia Services for 22,500 inpatient & outpatient procedure per year Acute Pain Service provides services to 2,500 patients annually Andrew Zimmerman, MD Assistant Clinical Professor of Anesthesia; Chief, Anesthesia Division Nathan Brakke, MD Assistant Clinical Professor of Anesthesia Krista Bockstahler, MD Clinical Instructor of Anesthesia Alyssa Brzenski, MD Clinical Instructor of Anesthesia Edgar Canada, MD Clinical Instructor of Anesthesia MAJOR PLANS AND GOALS To invite fellows to participate in the Multidisciplinary Critical Care Knowledge Assessment Program (MCCKAP) examination, a national test of core Critical Care knowledge To provide support for new programs, such as Cardiac Transplant, with minimal interrution in operating room efficiency and scheduling To provide Acute Pain Services to our inpatients using multi-modal resources Brock Fisher, MD Assistant Clinical Professor of Anesthesia David Frankville, MD Associate Clinical Professor of Anesthesia Scott Gillin, MD Clinical Instructor of Anesthesia Josh Gordon, MD Assistant Clinical Professor of Anesthesia Gloria Hwang, MD Clinical Instructor of Anesthesia To support research by critical care attendings and fellows: Encourage all critical care fellows to identify and submit a research project to the IRB by the end of their first year of training Improve the number of fellow research projects submitted for presentation at a national meeting To improve national recognition for the Critical Care Program: Increase the program s presence at national meetings through committee involvement, speaking and participation Kathleen Kaya, MD Assistant Clinical Professor of Anesthesia Sidney Merritt, MD Associate Professor of Anesthesia Daniel Ness, MD Assistant Clinical Professor of Anesthesia Christine Nieman, MD Assistant Clinical Professor of Anesthesia Karim Rafaat, MD Clinical Instructor of Anesthesia 46 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 47

25 FACULTY for the care each patient receives in the PICU. In addition, the medical team is responsible for the care of patients located outside of the PICU that are still on the PICU service. This may include trauma patients, as well as patients who have been transferred from the PICU to other areas of the hospital. A critical care faculty member leads daily bedside patient care rounds. These rounds consist of an in-depth review of all pertinent radiological tests, laboratory data, and clinical data and all medical and surgical consulting opinions. A plan of care for the day is determined during rounds. In addition, the critical care faculty members provide consultations on patients in other care areas when requested, and attend trauma activations as integral members of the trauma team. The PICU participates in an international program (VPS) that reviews observed and predicted (based on severity of illness scores, PRISM) morbidity and mortality, as well as other care indicators major PICUs across the country and internationally. The PICU is consistently ranked in the top few programs for observed:predicted mortality rates. TEACHING ACTIVITIES Alex Rodarte, MD Associate Clinical Professor of Anesthesia Sandra Saw, MD Assistant Clinical Professor of Anesthesia Robert Spear, MD Assistant Clinical Professor of Anesthesia Josh Gordon, MD Assistant Clinical Professor of Anesthesia Clay Stanley, MD Clinical Instructor of Anesthesia Each Anesthesia attending is responsible for teaching Anesthesia residents from UCSD and Navy Medical Center, San Diego. In addition, the Division trains respiratory therapists, emergency medical technicians, medical students, emergency medicine fellows, and pediatric residents, in airway management. In the Critical Care Division, each faculty member is responsible for teaching critical care fellows, nurse practitioners, residents and non-physician staff while on the clinical service in the PICU. Teaching may take place during patient care rounds or at the bedside with new admissions. In addition, each faculty member is responsible for presenting several didactic talks for the fellows throughout the year. The UCSD Pediatric Residents, and the RCHSD Pediatric Emergency Department fellows spend time in the PICU and the critical care attending physician is responsible for their training. RESEARCH ACTIVITIES Jennifer Ting, MD Assistant Clinical Professor of Anesthesia George Ulma, MD Clinical Instructor of Anesthesia 48 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Karen Vanderwall, MD Assistant Clinical Professor of Anesthesia Vinit Wellis, MD Assistant Clinical Professor of Anesthesia Michael Worthen, MD Assistant Clinical Professor of Anesthesia Not Pictured: Alvin Faierman, MD, Michael Flynn, MD, Mark Greenberg, MD, Daniel Lee, MD and William Ronan, DO, Kai Trong, MD, Anthony Stanzi, MD, Chien Chow, MD Natalie Darro, MD Nhat Pham, MD Edward Ferenczy, MD Joseph Treister, MD Nicole Coufal, MD PhD The Division of Anesthesia provides anesthesia care to patients in the 16-room Acute Care Pavilion Operating Room Suites, 4 procedure rooms in the Outpatient Procedure Center, the Sharp and Children s Hospital- San Diego MRI Center, the Cardiac Catheterization lab, 2 CT scanners, hematology-oncology procedure center, and to those receiving special procedures that must be performed at Sharp Memorial Hospital. The Division provides services for all major surgical procedures including congenital heart surgery, major orthopedic surgery, trauma, and organ transplants. Dr. George Ulma is the Medical Director of the Acute Pain Service, which provides consultation for post-operative and oncology patients. The Division presents an annual pain conference at RCHSD, in POSTDOCTORAL FELLOWS CLINICAL ACTIVITIES Yudy Fonseca, MD Andrea Guardenier, MD Whitney Law, MD Erin Ricker, MD addition to the ongoing pain resource nurse course. A multidisciplinary team led by the attending critical care physician treats critical care patients in the PICU. This team includes nursing, respiratory therapy, pharmacy, social work, child life, the case manager and chaplaincy. Nutrition support, occupational therapy, physical therapy and speech therapy also join the multidisciplinary team when needed. The medical team in the PICU includes the attending physicians, critical care fellows, critical care nurse practitioners and resident physicians. The PICU is a closed unit, which means that the critical care medical team coordinates care given by all medical and surgical sub-specialists, and is ultimately responsible Susan Duthie, MD, FAAP is currently investigating how to differentiate patients with Kawasaki disease and shock from other patients with shock on admission to the PICU. Dr. Duthie is also studying whether the use of antibiotics with open and/or depressed skull fractures reduces associated infectious complications and risk factors for intracranial bleeding after cardiopulmonary bypass. Brock Fisher, MD research interests include investigating the role of serum D-dimer to predict the absence of significant brain injury after head trauma in children. Additionally, Dr. Fisher has been researching the role of acupuncture for postoperative tonsillectomy pain. Michael Flynn, MD, FAAP, FCCM has been a consultant for many medical devices including warming technology and devices used for maintaining the airway during surgery. Sandeep Khanna, MD, FAAP has many research interests including traumatic brain injury and the evaluation of an age-based formula and physical exam for placement of endotracheal tubes in children. Bradley Peterson, MD, FAAP, FCCM has been researching complications associated with prolonged hypertonic saline therapy in children with elevated intracranial pressure. He has been a contributing investigator on a retrospective review evaluating the secondary brain insults during interfacility transport of pediatric trauma patients. and an investigator on a prospective study researching the use of thromboelastography to diagnosis coagulopathy after traumatic brain injury. Helen Harvey, MD research interests include predictors of progression of traumatic brain injury, cardiopulmonary resuscitation and use of simulation in critical care. Michael Worthen, MD research interests include liver disease in Fontan patients and other congenital cardiovascular topics. PUBLICATIONS Nakagawa TA, Duthie SE, et al: Guidelines for the determination of brain death in infants and children: An update of the 1987 Task Force recommendations. Crit Care Med, 39(9): , Shellington D, Du L, Wu X, Exo J, Vagni V, Ma L, Janesko-Feldman K, Clark RSB, Bayir H, Dixon CE, Jenkins L, Hsia C, Kochanek P. Polynitroxylated pegylated hemoglobin: A novel neuroprotective hemoglobin for acute volume-limited fluid resuscitation after combined traumatic brain injury and hemorrhagic hypotension in mice. Crit Care Med, 39(3): , Colasacco C, Worthen M, Peterson B, Lamberti J, Spear R: Nearinfrared spectroscopy monitoring to predict post-operative renal insufficiency following repair of congenital heart disease. World J for Pediatr and Congenit Heart Surg, 2(4): , Reuter-Rice K, Duthie S, Hamrick J: Neurogenic pulmonary edema associated with pediatric status epilepticus. Pediatr Emerg Care, 27(10):957-8, Hemerka JN, Wu X, Dixon CE, Garman RH, Exo JL, Shellington DK, Blasiole B, Vagni VA, Janesko-Feldman K, Xu M, Wisniewski SR, Bayer H, Jenkins LW, Clark RS, Tisherman SA, Kochanek PM: Severe brief pressure-controlled hemorrhagic shock after traumatic brain injury exacerbates functional deficits and long-term neuropathological damage in mice. J Neurotrauma, 29(12): , Shellington, DK. Lessons learned from afar: Coagulopathy and shock in pediatric battlefield trauma. Pediatr Crit Care Med, 13(3): Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 49

26 , Gargas J, Yaszay B, Kruk P, Bastrom T, Khanna S, Shellington D: An analysis of cervical spine magnetic resonance imaging findings after normal computed tomographic imaging findings in pediatric trauma patients: ten-year experience of a level I pediatric trauma center. J Trauma Acute Care Surg, 74(4):1102-7, Kochanek PM, Dixon CE, Shellington DK, Shin SS, Bayir H, Jackson EK, Kagan VE, Yan HQ, Swauger PV, Parks SA, Ritzel DV, Bauman R, Clark RS, Garman RH, Bandak F, Ling G, Jenkins LW: Screening of Biochemical and Molecular Mechanisms of Secondary Injury and Repair in the Brain after Experimental Blast-Induced Traumatic Brain Injury in Rats. J Neurotrauma, 30(11):920-37, Nieves D, Bradley JS., Gargas J, Mason W, Lehman D, Lehman SM, Murray EL, Harriman, K, Cherry JD: Exchange Blood Transfusion In The Management of Severe Pertussis In Young Infants. Pediatr Infectious Dis J, 32:6, p , Gonda DD, Meltzer HS, Crawford JR, Hilfiker ML, Shellington DK, Peterson BM, Levy ML: Complications associated with prolonged hypertonic saline therapy in children with elevated intracranial pressure. Pediatr Crit Care Med, 14 (6): , Johnson PN, Benefield EC, Bui PN, Gausman JN, Marlar RA, Gessouroun MR. Fondaparinux monitoring: need for a local fondaparinux-calibrated anti-factor Xa assay. J Pediatr Pharmacol Ther 2013;18(4): PMID: Johnson PN, Benefield EC, Bui PY, Marlar RA, Gessouroun MR. Fondaparinux in an obese child with heparin-induced thrombocytopenia and a history of renal failure. J Pediatr Pharmacol Ther Oct;18(4): PMID: Shein SL, Shellington DK, Exo JL, Jackson TC, Wisniewski SR, Jackson EK, Vagni VA, Bayır H, Clark RS, Dixon CE, Janesko- Feldman KL, Kochanek PM. Hemorrhagic shock shifts the serum cytokine profile from pro- to anti-inflammatory after experimental traumatic brain injury in mice. J Neurotrauma Aug 15;31(16): PMID: Law W, DiBardino DJ, Raviendren R, Devaney E, Davis C. Anomalous aortic origin of the left coronary artery: in-hospital cardiac arrest and death despite bed rest. World J Pediatr Congenit Heart Surg Oct;5(4): PMID: Shellington DK. Connecting the dots: from time point to trajectory analysis of serum sodium levels in pediatric neurologic injury. Pediatr Crit Care Med Nov;15(9): PMID: Clark, RF, O Connell, CW, Villano JH, Kim, A, Ly, BT, Minns AB. Severe Recurrent Coagulopathy Following Crotaline Envenomation Refractory to Maintenance Dosing of Antivenom. Am J Emerg Med Jun;33(6):856.e-856.e5. PMID: Pannell D, Poynter J, Wales PW, Tien H, Nathens AB, Shellington D. Factors affecting mortality of pediatric trauma patients encountered in Kandahar, Afghanistan. Can J Surg Jun;58(3):S PMID: Newell E, Shellington DK, Simon DW, Bell MJ, Kochanek PM, Feldman K, Bayir H, Aneja RK, Carcillo JA, Clark RS. Cerebrospinal Fluid Markers of Macrophage and Lymphocyte Activation After Traumatic Brain Injury in Children. Pediatr Crit Care Med Jul;16(6): PMID: Rudinsky SL, Sharieff GQ, Law W, Kanegaye JT. Inpatient Treatment after Multi-Dose Racemic Epinephrine for Croup in the Emergency Department. J Emerg Med Oct;49(4): doi: /j. jemermed Epub 2015 Aug 1. PMID: Reuter-Rice K, Patrick D, Kantor E, Nolin C, Foley J. Characteristics of Children Who Undergo Intraosseous Needle Placement. Adv Emerg Nurs J Oct-Dec;37(4): doi: / TME PMID: BOOK CHAPTERS Duthie S. Current and Controversial Traumatic Brain Injury Treatment Strategies, in Concepts in Pediatric Critical Care. Edited by P Spinella, T Nakagawa. Society of Critical Care Medicine, Mount Prospect, Illinois, 2010: p O Brien NF. Traumatic Brain Injury, in Pediatric Acute Care: A Guide for Interprofessional Practice, edited by K. Reuter-Rice, B. Bolick. Jones & Bartlett, Boston, 2011: p Hamrick J, Fuller Jennie. Cardiovascular Agents, in Pediatric Acute Care: A Guide for Interprofessional Practice, edited by K. Reuter-Rice, B. Bolick. Jones & Bartlett, Boston, 2011: p Hamrick J, Fuller Jennie. Cardiothoracic Trauma, in Pediatric Acute Care: A Guide for Interprofessional Practice, edited by K. Reuter-Rice, B. Bolick. Jones & Bartlett, Boston, 2011: p Nathalang D. Viral Infections, in Pediatric Acute Care: A Guide for Interprofessional Practice, edited by K. Reuter-Rice, B. Bolick. Jones & Bartlett, Boston, 2011: p Meadows B. Bites, in Pediatric Acute Care: A Guide for Interprofessional Practice, edited by K. Reuter-Rice, B. Bolick. Jones & Bartlett, Boston, 2011: p Meadows B. Stings, in Pediatric Acute Care: A Guide for Interprofessional Practice, edited by K. Reuter-Rice, B. Bolick. Jones & Bartlett, Boston, 2011: p Worthen HM. Cardiogenic Shock, in Pediatric Acute Care: A Guide for Interprofessional Practice, edited by K. Reuter-Rice, B. Bolick. Jones & Bartlett, Boston, 2011: p Peterson B, Duthie S. Pediatric Trauma, in Textbook of Critical Care, 6th Edition, edited by JL Vincent, et al. Elsevier Saunders, Philadelphia, 2011: p Nathalang D, Peterson B, Pulmonary Edema, in Textbook of Clinical Pediatrics, 2nd Edition. Edited by AY Elzouki, HA Harfi and H Nazer, FB Stapleton, W Oh, RJ Whitley. Springer-Verlag Berlin and Heidelberg GmbH & Co. K, 2012:p Wilder MS, Stucky ER. Near Drowning and Drowning, in in Textbook of Clinical Pediatrics, 2nd Edition. Edited by AY Elzouki, HA Harfi and H Nazer, FB Stapleton, W Oh, RJ Whitley. Springer-Verlag Berlin and Heidelberg GmbH & Co. K, 2012:p ABSTRACT PRESENTATIONS Gargas J, Yaszay B, Kruk P, Bastrom T, Khanna S: Cervical spine computed tomography scan, is this sufficient to clear cervical spine precautions in pediatric trauma patients? 18 th International Meeting on Advanced Spine Techniques. Copenhagen, Denmark. July 13-16, Gargas J, Yaszay B, Kruk P, Bastrom T, Khanna S: Cervical spine computed tomography scan, is this sufficient to clear cervical spine precautions in pediatric trauma patients? 46 th Annual Scoliosis Research Society Meeting, Louisville, KY. September 9-14, Recalde F, Fisher B, Spear, R, Peterson B: Serum D-Dimer Level Predicts Absence of Significant Brain Injury After Trauma In Children. Poster presentation at the American Academy of Pediatrics National Conference and Exhibition. Boston, MA October 15-18, Pediatr Crit Care Med 12(6):707 Gargas J, Yaszay B, Kruk P, Bastrom T, Khanna S: Cervical spine computed tomography scan, is this sufficient to clear cervical spine precautions in pediatric trauma patients? American Academy of Orthopedic Surgeons, 2012 Annual Meeting. San Francisco, CA February 7-11, Bush R, Freedman AJ, Shellington D, Senac M, Worthen M, Hilfiker M: Analysis Of Indications For Repeated Computed Tomography Scans After Inter-Facility Transfer Of Pediatric Trauma Patients. Poster presentation at the 19 th Pediatric Critical Care Colloquium. Santa Monica, CA September 6-9, Pediatr Crit Care Med. 13(6):719, November Frugoni B, Khanna S, Bush R, Peterson B, Shellington D: Endotracheal Tube Exchange in Pediatric Patients After Transfer From Non-Pediatric Facilities. Poster presentation at the Society of Critical Care Medicine, 42nd Critical Care Congress, San Juan, Puerto Rico, January 19-23, Crit Care Med. 40(12):445, December Harvey H, Malicki D, Bush R, Hilfiker M, Peterson B, Shellington D: Thromboelastography Reveals Abnormalities Not Detected on Traditional Coagulation Studies After Pediatric Traumatic Brain Injury. Poster presentation at the Society of Critical Care Medicine, 42nd Critical Care Congress, San Juan, Puerto Rico, January 19-23, Crit Care Med. 40(12):227, December Tran B, Harvey H, Shellington DK: 1139, A Tale of Two Detergent Pod Ingestions: Common Features of Critical Illness. Poster presentation at the Society of Critical Care Medicine, 43 rd Critical Care Congress, San Francisco, CA, January 9-13, Crit Care Med. 41(12) (Supplement 1):A288-A289, December Harvey H, Shellington DK. Transient Diabetes Insipidus in an 8 Year old with a Concussion: A Case Report. 43rd Critical Care Congress, January 10-14, San Francisco, CA. Crit Care Med (Supp): 41(12): A338-A339, December Tran B, Shellington D, Hilfiker M, Grabowski J. Laparotomy After Pediatric Trauma at a Level I Trauma Center. Poster presentation the Pediatric Trauma Society, Inaugural Meeting, Chicago, IL, November 14-15, Tran B, Grabowski J, Hilfiker M, Shellington D. Intensive Care Utilization of Pediatric Patients Undergoing Laparotomy After Abdominal Trauma. Poster presentation at the Society of Critical Care Medicine, 44th Critical Care Congress, Phoenix, AZ, January 17-21, Crit Care Med 42(12) (Supplement 1):A1621-A1622, December Tran B, Guardenier A, Khanna S, Shellington D. Asystolic Cardiac Arrest in Newly Diagnosed Juvenile Dermatomyositis. Poster presentation at the Society of Critical Care Medicine, 44th Critical Care Congress, Phoenix, AZ, January 17-21, Crit Care Med 42(12) (Supplement 1):A1635, December Bui PN, Foley J, Lamberti J, Nigam V; Vaughn G, Peterson B, Duthie S, Shellington D. Intracranial Hemorrhage After Cardiopulmonary Bypass for Correction of Congenital Heart Disease. Poster presentation at the Society of Critical Care Medicine, 44th Critical Care Congress, Phoenix, AZ, January 17-21, Crit Care Med 42(12) (Supplement 1):A1499, December Kim A, Foley J, Kantor E, Hilfiker M, Peterson B, Shellington D. Secondary Brain Insults During Interfacility Transport After Pediatric Traumatic Brain Injury. Poster presentation at the Society of Critical Care Medicine, 44th Critical Care Congress, Phoenix, AZ, January 17-21, Crit Care Med 42(12) (Supplement 1):A1499, December Bui PN, Lesser D, Shellington D, Worthen HM. Administration of sevoflurane to treat severe bronchospasm. Poster presentation at the Society of Critical Care Medicine, 44th Critical Care Congress, Phoeniz, AZ, January 17-21, Crit Care Med 42(12) (Supplement 1):A1635, December Harvey H, Duthie S, Cannavino C, Hilfiker M, Peterson B, Shellington D. Infectious complications after open, depressed skull fractures do not vary with choice of antibiotic prophylaxis regimen. Poster presentation at the 2015 Surgical Infection Society meeting in Westlake Village, CA, April 15 18, ORAL PRESENTATIONS Ochi, JW, Raviendran R, Fisher B. Oral presentation: Acupuncture Reduces Tonsillectomy Pain: A Prospective, Randomized Trial Preliminary Report. AAMA 24 th Annual Symposium in Atlanta, GA. April 29, Khanna, S. Invited Speaker. Oral presentation: Advances in Management of Respiratory Failure. Jaipur Heart Institute. Jaipur, India. March 23, Shellington DK: Therapeutic Hypothermia: Is it Still Cool to Cool? Contemporary Forums Pediatric Critical Care Nursing Conference, October 27-30, 2013, Las Vegas, NV. Shellington DK: Pediatric Traumatic Brain Injury: From Cellular Pathology to Clinical Guidelines. Contemporary Forums Pediatric Critical Care Nursing Conference, October 27-30, 2013, Las Vegas, NV. Khanna, S. Invited Speaker. Oral presentation: Inotrope Use in the PICU. Narayana Hrudayalaya hospital, Jaipur. Jaipur, India. February, 2014 Khanna, S. Invited Speaker. Oral presentation: Post-Operative Issues After Arterial Switch. Indian Association of Cardiovascular and Throacic Surgeons, Technocollege. Jaipur, India. March, Worthen M. Invited Speaker. Oral presentation: Anesthesia Specifics for Arterial Switch. Indian Association of Cardiovascular and Throacic Surgeons, Technocollege. Jaipur, India. March, AWARDS Selected for the Frist Prize Award in the Annual Research Paper Competition. Ochi, JW, Raviendran R, Fisher B: A Prospective, Randomized Trial Preliminary Report. AAMA 24 th Annual Symposium in Atlanta, GA. April 26-29, 2012 GRANTS Grant/Contract # Annual Budget Total Direct Dollars/Duration of Grant Manchester Family Fellow in Critical Care $300, present Approaches and Decisions for Acute Pediatric Traumatic Brain Injury (ADAPT), NIH U01NS A1; 7/1/2013-6/30/ UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 51

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27 Dermatology 52 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 53

28 INTRODUCTION The Division of Pediatric and Adolescent Dermatology is one of the largest pediatric dermatology units in the United States, and is a highly respected center with a national and international reputation for clinical, research and educational excellence. The academic years were very successful for the division, with significant contributions to the fields of dermatology and pediatrics in research, leadership, and advocacy, and expansion of the clinical services. FACULTY The Division exceeded 20,000 patient visits and over 1,500 surgical, laser and phototherapy procedures per year, with services in satellite clinics throughout San Diego County, including Oceanside, Murrieta, Encinitas and Escondido. The research program broadened its research work in inflammatory skin disease (including eczema, psoriasis and acne), genetic skin disorders, hemangiomas, skin tumors, and procedural dermatology. Division members have held significant senior national leadership positions, including Dr. Sheila Friedlander as a Board of Director member of the American Academy of Dermatology, Dr. Lawrence Eichenfield as Co-Chair of the Pediatric Dermatology Research Alliance (PeDRA), and Dr. Wynnis Tom as Head of the PeDRA Inflammatory Skin Disease Research Group as well as Director of the PeDRA Annual Research Meetings. In addition, Dr. Victoria Barrio is leading a multi-institutional study on facial hemangiomas and their syndromic risks. Dr. Magdalene Dohil has lectured internationally, including the New Zealand Dermatology Society Meeting. Dr. Catalina Matiz joined the faculty, bringing her expertise as one of the few national experts in pediatric contact allergy. The Scar Treatment and Revision (STAR) Program has performed cutting edge research with new laser technologies for the treatment of pediatric scars, including traumatic, post-surgical, birthmark-associated and burn scars. This work is leading to transformative practices in the management of functionally significant and deforming scars. Lawrence F. Eichenfield, MD Professor of Clinical Pediatrics and Medicine Director Sheila Fallon Friedlander, MD Professor of Clinical Pediatrics and Medicine Magdalene A. Dohil, MD Associate Professor of Clinical Pediatrics and Medicine Victoria R. Barrio, MD Associate Clinical Professor and Medicine The Vascular Lesion and Birthmark Center maintains its reputation as a regional and national resource for the evaluation, management and study of hemangiomas, vascular malformations, pigmented and other cutaneous birthmarks. The Center s services include multidisciplinary clinics with experts in dermatology, laser and plastic surgery, diagnostic and interventional radiology, otorhinolaryngology, pathology, ophthalmology and orthopedics. A hematology-oncology expert has also joined the center, as medical therapies are becoming therapeutic options with the marked rise in discovery of genes underlying these lesions. The Eczema and Inflammatory Skin Disease Center, the first program of its type in the nation, continues to evolve in clinical care, education, and research in atopic dermatitis, psoriasis, acne and other inflammatory diseases of childhood and adolescence. The Division is an international leader in the study of new topical and systemic medications for the treatment of atopic dermatitis, psoriasis, and acne. The division s diverse faculty members also specialize in procedural dermatology, cutaneous infections, genetic diseases, nevi (moles) and skin cancer, as well as initiatives for disease prevention and to improve skin health over a lifetime. In addition, the Division is pleased to include three physician assistants in the practice. The Division is developing a Rare Skin Disease Program, highlighting utilizing state of the art techniques in the diagnosis and research of genetic skin conditions, including epidermolysis bullosa, ichthyoses, and mosaic disorders, with hope of contributing to targeted therapies. MAJOR PLANS AND GOALS To provide exceptional educational experiences for fellows, residents, medical students, and allied health providers. We also plan to Center Development Eczema and Inflammatory Skin Disease Center: The Center is continuing to innovate new methods for educating patients, families, physicians and other health care workers, including evolving web-based learning modules, videos, and web 2.0 and 3.0. The research program includes significant genomics initiatives such as the NIH-sponsored research on psoriasis of Dr. Wynnis Tom, as well as the study of disease impact and comorbidities in inflammatory skin diseases including atopic dermatitis and acne. The Center is also a leader in the development of a pediatric dermatology collaborative research group PEDRA (PEdiatric Dermatology Research Alliance) for the study of inflammatory skin disease and comparative effectiveness studies. Dr. Tom is leading a multi-center study of systemic therapy for atopic dermatitis, utilizing web-based collaborative data entry as well as patient-oriented outcome measures. The Vascular Lesion and Birthmark Center is expanding its services, which includes the multi-disciplinary vascular lesion clinic and collaborative clinics with plastic surgery for the evaluation and management of congenital and acquired skin anomalies. The Center was recently named a Sturge-Weber Foundation Center of Excellence, reflecting the expertise in management of port-wine stains and associated syndromes, as well as complex vascular malformations. The laser program expansion continues, with the addition of new laser technology for refractory blood vessel birthmarks. The Center is a leader in utilizing new fractionated laser devices for the treatment of surgical and traumatic scars in children, in collaboration with Naval Medical Center dermatologistlaser surgeons, This new program has the potential to improve the lives of thousands of children, minimizing the physical and psychosocial impact and effects of trauma and disfigurement. The division is exploring the development of a Pediatric Photomedicine and Laser Center, dedicated to research and clinical care utilizing lasers and light-based therapies. Faculty Development The recruitment of two to three faculty members is planned for the next four-year period. A national search is underway for pediatric dermatologists with interests and expertise in laser and procedural dermatology, as well as physician-scientists and clinical experts in pediatric dermatology. Wynnis L. Tom, MD Associate Clinical Professor and Medicine PRACTITIONERS Eliza Barrett, PA-C Stephanie Link, PA-C Brianne Wagenman, PA-C Andrew C. Krakowski, MD Assistant Clinical Professor and Medicine Richard L. Gallo, MD, PHD Associate Professor of Clinical Pediatrics and Medicine Photos not available: Catalina Matiz, MD (Assistant Clinical Professor) and Susan Boiko, MD (Associate Clinical Professor,Voluntary) FELLOWS Luluah Almabubarak, MD (Clinical) Jusleen Ahluwalia, MD (Research) Carol Cheng, MD (Clinical) Nancy Cheng, MD (Clinical) Pamela Gangar, MD (Research) Emily Osier, MD (Research) Brenda Simpson, MD (Clinical) Jessika Valderamma, MD (Clinical) 54 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 55

29 The Division had over 20,000 ambulatory visits each year, with services provided at five locations: Rady Children's Hospital campus and satellite clinics at Encinitas, Escondido, Oceanside, and Murrieta. There were over 1,500 surgical, laser and phototherapy procedures performed annually. The Division has been named a Center of Excellence by the Sturge-Weber Foundation. The Vascular Lesion and Birthmark Center has expanded multidisciplinary activities including laser, interventional radiology, and birthmark surgery services. The Division continues to investigate optimal methods for management of atopic dermatitis, including studying the best intensive education techniques to minimize the impact of the disease on affected individuals and their families. Dr. Wynnis Tom runs a specialty clinic for children with severe atopic dermatitis requiring systemic therapy. Dr. Matiz holds a comprehensive patch testing clinic for complex cases of allergic contact dermatitis, particularly those with concomitant atopic dermatitis. The physicians in the division have advanced training in the expert diagnosis and management of common and uncommon skin conditions, which include: Eczema, psoriasis and other inflammatory skin disorders Hemangiomas, vascular malformations, and other birthmarks Acne Warts and molluscum contagiosum Bacterial, viral and fungal infections of the skin, hair, and nails Genodermatoses Moles (nevi), melanoma and other skin malignancies Congenital and acquired tumors The Division continues its diverse national and international education activities; RCHSD and UCSD have perhaps the most extensive training program for pediatric dermatology in the nation. The Division of Pediatric Dermatology at RCHSD is affiliated with both the Department and the Department of Medicine (Dermatology) at UCSD. The Pediatric Dermatology Fellowship Program was introduced in Based at RCHSD, fellows are involved in clinical activities and research involving pediatric dermatology. The clinical program involves ambulatory dermatology clinics and inpatient consultations at RCHSD, UCSD Hillcrest and Sharp Mary Birch Hospital. The programs have trained more than 280 dermatology residents and 45 fellows (in addition to hundreds of pediatric residents). Pediatric dermatology fellows are also actively involved in research during their fellowship years. These trainees enhance the program and contribute to the advancement of the field of pediatric dermatology through research and education. The Division of Pediatric and Adolescent Dermatology offers specialized clinical training, clinical and basic research, teaching and other academic activities to develop individual expertise and allow CLINICAL ACTIVITIES The Division continues to be a leader in inflammatory skin disease research. Multiple studies of new therapeutic agents, as well as therapies for pre-adolescent acne, have been led by Dr. Eichenfield. Dr. Eichenfield also serves as a member of the NIAID Expert Panel on Food Allergy. Dr. Wynnis Tom is completing her NIH K23 award to study the genetic influences of pediatric psoriasis. She has established the first pediatric psoriasis DNA bank to study disease pathogenesis and test potential biomarkers for course and therapeutic response. 56 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report TEACHING ACTIVITIES RESEARCH ACTIVITIES The members of the division have internationally recognized expertise in laser and dermatologic surgery for children and adolescents. Therapies utilized include topical and systemic drugs, cryosurgery, laser therapy and dermatologic surgery. Surgical services are performed in-office or in the Surgery Center at RCHSD, and state-of-the-art pain relief techniques are utilized during procedures. The Eczema and Inflammatory Skin Disease Center specializes in comprehensive clinical care, education of patients, families and health care professionals, and research on atopic dermatitis, psoriasis, acne and other inflammatory skin diseases. The center integrates basic and clinical research into its care, and emphasizes medical, educational and emotional support as part of its therapeutic interventions. Highlights of the Center s activities include its influential web presence, including video training modules. The center has pioneered novel therapeutic and education approaches, and is a world leader in the study of eczematous dermatitis. The center has instituted the development and testing of new therapies for treatment and approaches to improve clinical outcomes, and the initiation of standardized train the trainers atopic dermatitis education, to improve the consistency of teaching about this common, chronic disease. In addition, the Center has extensive clinical and research activities related to pediatric psoriasis and acne, ranging from NIH-supported basic science to translational and clinical intervention studies. trainees to contribute to the fields of dermatology and pediatrics. Elective rotations are available for medical students and resident trainees in dermatology, pediatrics and other specialties. Divisional education conferences are held weekly, which include case reviews and Journal Club. Dr. Victoria Barrio oversees medical student and resident educational activities for the division. Dr. Sheila Fallon Friedlander co-chairs the national CME Skin Disease Education Seminar "Women's and Pediatric Dermatology" meeting, and won the coveted Speaker of the Day prize at the national Fall Clinical Dermatology meeting. Drs. Krakowski and Friedlander co-chaired the Pediatric Dermatology for the Practitioner CME meeting, with over 220 attendees. The entire faculty has participated as invited speakers in American Academy of Dermatology (AAD) national meetings, and multiple visiting professorships were carried out by senior faculty throughout the world. Both Drs. Wynnis Tom and Victoria Barrio have been awarded the prestigious Robert Goltz Teaching Prize of the UCSD Division of Dermatology. The first guidelines for screening children with psoriasis for comorbid conditions were created through the leadership of Drs. Eichenfield and Tom, working with members of a multidisciplinary expert panel. The guidelines have the support of the National Psoriasis Foundation and the Pediatric Dermatology Research Alliance (PeDRA). Drs. Eichenfield, Tom, and Matiz are members of the American Academy of Dermatology's Atopic Dermatitis Expert Resource Group. Dr. Eichenfield co-chairs the PeDRA Skin Tumor and Related Condition Group(STARC), which directs multi-institutional research throughout the United States on melanoma, non-melanoma skin cancers, and other pediatric cutaneous tumors. Dr. Sheila Fallon Friedlander is a Principal Investigator of a study of topical timolol for infantile hemangiomas, as beta blockers have revolutionized the care of patients with these common vascular tumors. Dr. Eichenfield is Co-Chair of the Pediatric Dermatology Research Alliance (PeDRA), and Dr. Tom was recently selected to be Chair of the PeDRA Science Committee. This consortium is dedicated to developing collaborative research in pediatric dermatology, and has received NIH and other funding to establish this collaborative research network. Dr. Barrio received a PeDRA pilot grant to study facial hemangiomas to further delineate the risk for syndromic findings. Dr. Matiz is examining Staphyloccocal skin eruptions in children and antibiotic resistance in those with and without atopic dermatitis. Over 100 papers and textbook chapters have been published by the Division over the past years. Richard L. Gallo, MD, PhD, directs a basic science research program at UCSD that has NIH RO1 funding of approximately $1.5 million per year the largest program directed by a pediatric dermatologist in the United States. He is a leading investigator on the role of the innate immune system in skin health and disease, along with the microbiome and interactions between disease-causing bacteria and commensal organisms. PUBLICATIONS Krakowski AC, Admani S, Uebelhoer N, Eichenfield LF, Shumaker P. Residual scarring from hidradenitis suppurativa: Fractionated CO2 laser as a novel and non-invasive approach. Pediatrics [in press] Eichenfield LF, Krakowski AC, Piggott C, et al. Evidence-based recommendations for the diagnosis and treatment of pediatric acne. Pediatrics 2013;131 Suppl 3:S Shumaker PR, Dela Rosa KM, Krakowski AC. Treatment of lymphangioma circumscriptum using fractional carbon dioxide laser ablation. Pediatric Dermatology 2013;12. Admani S, Krakowski AC. An atypical presentation of neonatal lupus erythematosus. Journal of Clinical and Aesthetic Dermatology 2013;6(5): Krakowski AC, Ho B. Arthropod assault from biting midges: The all-you-can-eat buffet sign. Journal 2013;163(1):298. Eichenfield LF, Krakowski AC. Moderate to severe acne in adolescents with skin of color: benefits of a fixed combination clindamycin phosphate 1.2% and benzoyl peroxide 2.5% aqueous gel. Journal of Drugs in Dermatology 2012;11(7): Admani S, Krakowski AC, Nelson JS, Eichenfield LF, Friedlander SF. Beneficial effects of early pulsed dye laser therapy in patients with infantile hemangiomas. Dermatologic Surgery 2012;38(10): Krakowski AC, Eichenfield LF. The use of resurfacing, pigment, and depilation lasers in children. In: Irvine A, Hoeger P, and Yan A, eds. Harper s Textbook of Pediatric Dermatology. Chapter 189, 3 rd ed. Hoboken, New Jersey: Blackwell Publishing Ltd., Krakowski AC, Kaplan L. Sun exposure and photo-medicine. In: Auerbach P, ed. Wilderness Medicine, 6 th ed. Maryland Heights, Missouri: Mosby Elsevier, Dohil M. Atopic Dermatitis and Other Inflammatory Skin Disease Natural Ingredients for Skin Care and Treatment. J of Drugs in Dermatology Sept;10(9):s6-s9 (Supplement). Melancon JM, Dohil MA, Eichenfield LF.Facial port-wine stain: when to worry? Pediatr Dermatol Jan-Feb;29(1): doi: /j x. No abstract available. Schmitt J, Spuls P, Boers M, Thomas K, Chalmers J, Dohil M, et al. Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting. Allergy Sep;67(9): Epub 2012 Jul 30 Trevino J, Grosshandler J, Chen AY, Chiang C, Serrao R, Dohil M. Multiples in dermatology: markers for special considerations in diagnosis, therapy, and prognosis. J Drugs Dermatol Jul;11(7): Review. Schmitt J, Spuls P, Boers M, Thomas K, Dohil M, et al. Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting. Allergy Sep;67(9): Herro EM, Friedlander SF, Jacob SE. Violin Bow-Associated Rubber Allergy in a Child. Dermatitis Aug 1;22(4): No abstract available. Breithaupt A, Friedlander SF. A Comparative Trial Evaluating the Efficacy of Tacrolimus 0.1% Ointment versus Aquaphor ointment for The Treatment of Keratosis Pilaris. Pediatr Dermatol Jul- Aug;28(4): doi: /j x. Baldwin HE, Friedlander SF, Eichenfield LF, Mancini AJ, Yan AC. The effects of culture, skin color, and other nonclinical issues on acne treatment. Semin Cutan Med Surg Sep;30(3 Suppl):S12-5. Yan AC, Baldwin HE, Eichenfield LF, Friedlander SF, Mancini AJ. Approach to pediatric acne treatment: an update. Semin Cutan Med Surg Sep;30(3 Suppl):S Mancini AJ, Baldwin HE, Eichenfield LF, Friedlander SF, Yan AC. Acne life cycle: the spectrum of pediatric disease. Semin Cutan Med Surg Sep;30(3 Suppl):S2-5. Eichenfield LF, Mancini AJ, Yan AC, Friedlander SF, Baldwin HE. Parents as partners in pediatric acne management. Semin Cutan Med Surg Sep;30(3 Suppl):S22. No abstract available. Friedlander SF, Baldwin HE, Mancini AJ, Yan AC, Eichenfield LF. The acne continuum: an age-based approach to therapy. Semin Cutan Med Surg Sep;30(3 Suppl):S6-11. Herro EM, Friedlander SF, Jacob SE.Bra-Associated Allergic Contact Dermatitis: P-Tert-Butylphenol Formaldehyde Resin as the Culprit. Pediatr Dermatol Oct 20. doi: /j x. [Epub ahead of print] Gillis K, Bradley J, Friedlander SF. Persistent subcutaneous nodule: "Sealed with a Kiss". Pediatr Infect Dis J Dec;30(12):1119, Friedlander S. Further evidence that propranolol is effective in the treatment of infantile hemagiomas. J Pediatr Jan;160(1):173. Friedlander SF, Chan YC, Chan YH, Eichenfield LF. Onychomycosis Does Not Always Require Systemic Treatment for Cure: A Trial Utilizing Topical Therapy. Submitted, British Journal of Dermatology. Kanada K, Reyes-Merin M, Munden A, Friedlander SF. A prospective study of cutaneous findings in newborns in the United States: Correlation with race, ethnicity, and gestational status using updated classification and nomenclature. In press, Journal of Pediatrics. Admani S, Krakowski AC, Nelson JS, Eichenfield LF, Friedlander SF. Beneficial Effects of Early Pulsed Dye Laser Therapy in Individuals with Infantile Hemangiomas. Dermatol Surg Jul 9. [Epub ahead of print] No abstract available. Ho B, Friedlander SF. Developing a First-line Acne Treatment Plan Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 57

30 for Pediatric and Adolescent Patients. The Dermatologist, January Chen TS, Eichenfield LF, Friedlander SF. Infantile hemangiomas: an update on pathogenesis and therapy. Pediatrics Jan;131(1): Friedlander SF, Chan YC, Chan YH, Eichenfield LF. Onychomycosis does not always require systemic treatment for cure: a trial using topical therapy May-Jun;30(3): Eichenfield LF, Krakowski AC, Piggott C, Del Rosso J, Baldwin H, Friedlander SF, et al. Evidence-based recommendations for the diagnosis and treatment of pediatric acne. Pediatrics May;131 Suppl 3:S Tom WL, Kawasaki T, and Burns JC. Kawasaki Disease. In Textbook of Pediatric Dermatology. 3rd edition. Irvine AD, Höger P, and Yan AC, editors. Blackwell Publishing, Piggott C, Friedlander SF, and Tom WL. Pox Virus Infections. In Fitzpatrick s Dermatology in General Medicine. 8th edition. Goldsmith LA, Katz SI, Gilchrest B, Paller AS, Leffell DJ, and Wolff K, editors. McGraw-Hill Professional, Tom WL, Hurley MY, Oliver DS, Shah MR, Bree AF. Features of basal cell carcinomas in basal cell nevus syndrome. American Journal of Medical Genetics Sep;155(9): Melancon JM, Tom WL, Lee RA, Jackson M, Jiang SI. Management of pilomatrix carcinoma: a case report of successful treatment with Mohs micrographic surgery and review of the literature. Dermatologic Surgery Dec;37(12): Tom WL. Atopic dermatitis: recent findings and insights. Pediatric Annals Jan 13;41(1):e1-5. Chiu YE, Drolet BA, Blei F, Krol A, Lofgren S, Mancini AJ, Metry DW, Silverman RA, Tom WL, Pope E. Variable Response to Propranolol Treatment of Kaposiform Hemangioendothelioma and Tufted Angioma. Pediatric Blood & Cancer Nov;59(5): Caufield M and Tom WL. Oral Azathioprine for Recalcitrant Pediatric Atopic Dermatitis: Clinical Response and Thiopurine Monitoring. Journal of the American Academy of Dermatology. Journal of the American Academy of Dermatology Jan;68(1): Paller AS, Mercy K, Kwasny MJ, Choon SE, Cordoro KM, Girolomoni G, Menter A, Tom WL, Mahoney AM, Oostveen AM, Seyger MM. Association of pediatric psoriasis severity with excess and central adiposity: an international crosssectional study. JAMA Dermatology Feb;149(2): Dohil M. Atopic Dermatitis and Other Inflammatory Skin Disease Natural Ingredients for Skin Care and Treatment. J of Drugs in Dermatology Sept;10(9):s6-s9 (Supplement). Melancon JM, Dohil MA, Eichenfield LF.Facial port-wine stain: when to worry? Pediatr Dermatol Jan-Feb;29(1): doi: /j x. No abstract available. AWARDS AND PRESENTATIONS Victoria R. Barrio, MD Best Doctors in America, Co-Chair, Society for Pediatric Dermatology National Meeting, Spring 2012 Speaker, Pediatric Dermatology Jeopardy. American Academy of Dermatology Annual Meeting, New York, NY, August, 2011 Meeting Co-Chair, Society for Pediatric Dermatology, Pre-AAD Meeting, San Diego, CA, March, 2012 Speaker, Neonatal Dermatology, American Academy of Dermatology 70 th Annual Meeting, San Diego, CA March, 2012 Speaker, Management of Warts and Molluscum in Children My Treatment Approach, Mastering Advances in Dermatology, Greensboro, NC, March, 2012 Speaker, How I Treat Hemangiomas, Mastering Advances in Dermatology, Greensboro, NC, March, 2012 Speaker, Neonatal Dermatology, Pediatric Dermatology for the Practitioner, Philadelphia, PA, April, 2012 Speaker, To ER is Human, Pediatric Dermatology for the Practitioner, Philadelphia, PA, April, 2012 Speaker, Pediatric Dermatology Jeopardy, American Academy of Dermatology Summer Meeting, Boston, MA, August, 2012 Speaker, Pediatric Dermatology Pearls, Tennessee Dermatology Society Annual Meeting, Memphis, TN, November, 2012 Speaker, Growing up is hard to do, Pediatric Dermatology for the Practitioner, San Diego, CA. April 2013 Speaker, Dermatoses of Infancy, Kansas City Dermatologic Society Meeting, Kansas City, KS, June 2013 Magdalene A. Dohil, MD Co-Chair, Society for Pediatric Dermatology National Meeting, Spring 2012 Speaker, GI: The Skin and Gut Connection. Skin Disease Education Foundation: Women s and Pediatric Dermatology Seminar. September 23-25, San Francisco, CA Speaker, Lumps and Bumps. Skin Disease Education Foundation: Women s and Pediatric Speaker, Dermatology Seminar. September 23-25, San Francisco, CA. Speaker, Pediatric Dermatology Common and uncommon conditions to diagnose. Orlando Dermatology Aesthetic & Clinical Conference; January 13 th -16 th 2012 Speaker, Atopic Dermatitis: The use of TCI and Preliminary Data on Safety. Orlando Dermatology Aesthetic & Clinical Conference; January 13 th -16 th 2012 Speaker, Identifying Natural Ingredients and their Use in Skin Care. Orlando Dermatology Aesthetic & Clinical Conference; January 13 th -16 th 2012 Course Director, 24 th Annual Pre-AAD Meeting, Society for Pediatric Dermatology, San Diego, CA, March 15, 2012 Course Director, Pediatric Dermatology, 70 th Annual American Academy of Dermatology, San Diego, CA, March 16-20, 2012 Speaker, Atopic Dermatitis Forum: Measuring and Improving Outcomes. 70 th Annual American Academy of Dermatology, San Diego, CA. March 16-20, 2012 Speaker, Skin Tumors in Children: When to Worry. 70 th Annual American Academy of Dermatology, San Diego, CA. March 16-20, 2012 Speaker, Atopic Dermatitis: Current Concepts in Pathogenesis and Implications for Patient Management. New Zealand Dermatological Society Meeting, Queenstown, New Zealand, August 8-11, 2012 Speaker, Hemangiomas and Vascular Malformations. New Zealand Dermatological Society Meeting, Queenstown, New Zealand, August 8-11, 2012 Speaker, Pediatric Dermatology Case Studies. New Zealand Dermatological Society Meeting, Queenstown, New Zealand, August 8-11, 2012 Speaker, Skin Tumors in Children: When to Worry And When Not New Zealand Dermatological Society Meeting, Queenstown, New Zealand, August 8-11, 2012 Speaker, The Skin and Gut Connection. New Zealand Dermatological Society Meeting, Queenstown, New Zealand, August 8-11, 2012 Speaker, Pediatric Dermatology Workshop. Orlando Dermatology Aesthetic & Clinical Conference, Orlando, Florida, January 18-21, 2013 Speaker, Active Naturals in Dermatology for the Treatment of Inflammatory Skin Disease. Orlando Dermatology Aesthetic & Clinical Conference, Orlando, Florida, January 18-21, 2013 Speaker, Pediatric Cases from the Practice: What Would You Do? Orlando Dermatology Aesthetic & Clinical Conference, Orlando, Florida, January 18-21, 2013 Speaker, Atopic Dermatitis Current Concepts in Pathogenesis and Implications for Patient Care. Practical Pediatrics, Rady Children s Hospital San Diego. March 9, 2013 Speaker, Lumps and Bumps in Little Ones. Pediatric Dermatology for the Practitioner. Hilton La Jolla Torrey Pines, La Jolla, CA. April 5-6, 2013 Speaker, The Skin-Gut Connection. Pediatric Dermatology for the Practitioner. Hilton La Jolla Torrey Pines, La Jolla, CA. April 5-6, 2013 Lawrence F. Eichenfield, MD Editor-in-Chief, Pediatric Dermatology Best Doctors in America, Castle Connolly Medical Ltd., San Diego Top Doctors of Excellence, Dermatology and Pediatric Dermatology, Chair, American Academy of Dermatology Atopic Dermatitis Guidelines Task Force, President-Elect and President, Acne and Rosacea Society, Chair, Pedatric Acne Guidelines Study Group; American Acne and Rosacea Society 2011-present Visiting Professor Pro Tempore and Dr. Raul Fleischmajer Memorial Lecturer. Mount Sinai School of Medicine, Department of Dermatology, New York, NY. May 2012 Visiting Professor and Lecturer, Massachusetts General Hospital, Harvard Medical School, Boston Massachusetts. November, 2012 Visiting Professor, Dowling Club/Grand Round Dermatology Seminar Series; Atopic Dermatitis: Evolving Perspectives on Pathogenesis and Therapy, University of California-Irvine. Irvin, CA. April, 2013 Speaker, The New NIAID Food Allergy Guidelines: How do They Affect My Practice? Summer Academy Meeting of the American Academy of Dermatology. New York, NY. August 4-7, 2011 Speaker, Atopic Dermatitis, What s New? Colorado Dermatologic Society, Englewood, CO, September 23, 2011 Speaker, Atopic Dermatitis: Meeting the Clinical Challenge, and Cutaneous Challenges in Your Littlest Patients, Women's and Pediatric Dermatology Conference. San Francisco, CA. September 24, 2011 Speaker, Prevention of Atopic Dermatitis, and Acne-Update on Management. Excellence in Pediatrics. Istanbul, Turkey. December 2, 2011 Speaker, Inflammatory Issues in Little Ones, and Pediatric Dermatology Jeopardy. Advances in Cosmetic and Medical Dermatology. Maui, HI. February5-6, 2012 Pediatric Dermatology Session Chair and Speaker: What s Erupting in Acne, and What Would you Do: CASES, 36th Annual Hawaii Dermatology Seminar, February 22-24, 2012 Speaker, Acne: What s Erupting? Acne Update, What s New in Atopic Dermatitis, and Cutaneous Challenges in Your Littlest Patients (Workshop). 5th Annual Pediatric Allergy and Dermatology for the Practitioner. Whistler, British Columbia. March 9-11, 2012 Director, Forum F034, Atopic Dermatitis, and Speaker, Atopic Dermatitis: What s Hot, Food Allergy and Dermatology, Eczema and Food Allergies What s Real? and What s New in Pediatric Dermatology. 70th Annual American Academy of Dermatology Meeting. San Diego, CA. March 16-20, 2012 Speaker, Acne Update: What Zit All About, Rheum with a View, Challenging Cases in Pediatric Dermatology. Pediatric Dermatology for the Practitioner. Philadelphia, PA. April 20-21, 2012 Speaker, What s New in Pediatric Inflammatory Skin Disease? American Academy of Dermatology SAM (Summer Academy Meeting). Boston, MA. August 17, 2012 Speaker, Rashes in Kids, Coastal Dermatology Symposium. Napa, CA. September 28, 2012 Grand Rounds Speaker, Atopic Dermatitis: Insights into Pathogenesis and Therapy, Dell Children s Medical Center Dermatology Grand Rounds. Austin, TX. October 12, 2012 Speaker, Atopic Dermatitis What do I do Now? and Rheum With a View, Women s and Pediatric Dermatology Seminar. San Francisco, CA. October 20, 2012 Speaker, What s Erupting? Atopic Dermatitis: What s New and What s True? Hemangioma Update, and Cutaneous Challenges in Your Littlest Patients, Twenty-Ninth Annual Current Advances in Pediatrics (AAP California Chapter 4). Newport Beach, CA. November 2-3, 2012 Speaker, Spot the Rash, 25 th Annual Infectious Diseases in Children Symposium. New York, NY. November 17-18, 2012 Speaker, Atopic Dermatitis: What s New and True? and Acne What s Erupting? 10 th Sainte-Justine Pediatric Dermatology Day, Universite de Montreal. Montreal, Quebec. November 30, 2012 Grand Rounds Speaker, Atopic Dermatitis: Insights into Pathogenesis & Therapy, and Challenging Cases in Pediatric Dermatology, Grand Rounds and Resident Presentation, UC Davis School of Medicine Department of Dermatology Grand Rounds. Sacramento, CA. January 16, 2013 Speaker, Pediatric Dermatology Seminar and Acne & Rosacea Challenging Cases, Maui Derm 2013 Advances in Cosmetic & Medical Dermatology. Maui, HI. January 19-23, 2013 Speaker, Hot Topics in Pediatric Dermatology. Winter Clinical Dermatology Conference Hawaii. Koloa, HI. January 18-23, 2013 Speaker, What s Erupting: Pediatric Acne Update and What s Boiling Over: Atopic Dermatitis Update. SDEF Hawaii Dermatology Seminar. Maui, HI. February 13, 2013 Speaker, Advances in Pediatric Dermatology What s New? Pediatric Acne Management: Optimizing Outcomes, and Case Studies in Pediatric Dermatology Test Your Knowledge. 13 th Annual Winter Conference on Pediatrics. Big Sky, MT. February 19-21, 2013 Director, Forum F098 Atopic Dermatitis and Speaker, Psoriasis in Pediatric Patients, Treating Acne in Younger Children: An Overview of New Pediatric Acne Management Guidelines, Atopic Dermatitis Update and New Guidelines, Translating Evidence into Practice: Atopic Dermatitis and Guidelines for the Diagnosis and Management of Food Allergy, and Hemangiomas and Vascular Lesions. 71st Annual American Academy of Dermatology Meeting. Miami, FL. March 1-4, 2013 Grand Rounds Speaker, Vascular Lesion Laser Update, Department of Dermatology, University of California San Diego. San Diego, CA. March 28, 2013 Speaker, Breaking Out All Over, Look-Alikes: Mimickers You Need to Recognize, and Rheum with a View, Pediatric Dermatology for the Practitioner. San Diego, CA. April 5-6, 2013 Speaker, Atopic Dermatitis: What's New and True, Turning Red: Hemangioma Update, What's Erupting: Pediatric Acne Guidelines, and Cutaneous Challenges in Your Littlest Patients. Advances in Pediatrics CME Conference, California Chapter 2, American Academy. Las Vegas, NV. May 3-5, 2013 Sheila Fallon Friedlander, MD President, Society for Pediatric Dermatology Member, American Academy of Dermatology Board of Directors. Best Doctors in America, Castle Connelly Medical Ltd, San Diego Top Doctors of Excellence, Who s Who in America, President Elect, Society for Pediatric Dermatology, 2011 Program Director, Advanced Pediatric Dermatology, American Academy of Dermatology Annual Meeting, 2011 Chair, Skin Disease and Education Foundation Women s and Pediatric Dermatology Seminar, UCSD Division of Dermatology, The Robert W. Goltz, MD Excellence in Teaching Award, 2010 UCSD Academy of Clinician Scholars, 2010-Present Board of Directors, Children s Specialists of San Diego Holdings, 2010 America s Top Doctors/Best Doctors in America, Castle Connolly Medical Ltd, 2011 Medical Curriculum Committee, Dermatology Foundation, 2008 present 58 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 59

31 Speaker, Peds Derm Boot Camp: Basic Training-Acne and Warts. Women s and Pediatric Dermatology Seminar. San Francisco, CA. September 24-26, Speaker, Vitamin D: The Ongoing Controversy in Kids. Women s and Pediatric Dermatology Seminar. San Francisco, CA. September 24-26, Speaker, Cutaneous Abnormalities in Atopic Dermatitis. 30 th Anniversary Fall Clinical Dermatology Conference. Caesar s Palace, Las Vegas, NV. October 27-30, Speaker, The Challenge of Eczematous Rashes in Little Ones Then..and Now. 30th Anniversary Fall Clinical Dermatology Conference. Caesar s Palace, Las Vegas, NV. October 27-30, Speaker, Lumps and Bumps in the Pediatric Population When to Watch, When to Worry, When to Act! Advances and Approaches for the Dermatologic Practitioner. Grand Wailea Resort, Maui, HI. February 1-3, Speaker, The Challenge of Eczematous Rashes in Little Ones. Advances and Approaches for the Dermatologic Practitioner. Grand Wailea Resort, Maui, HI. February 1-3, Speaker, Pearls Perfectly Polished: New and Emerging Pedi Derm Diseases. 36 th Hawaii Dermatology Seminar, Maui, HI. February 4-8, Speaker,Lumps, Bumps and Procedural Pearls for the Tiny Tyke. 36 th Hawaii Dermatology Seminar, Maui, HI. February 4-8, Speaker, Panel Discussion: The Challenging Pediatric Patient. 36 th Hawaii Dermatology Seminar, Maui, HI. February 4-8, Speaker, Peds Derm Jeopardy Join the Winning Team! 36 th Hawaii Dermatology Seminar, Maui, HI. February 4-8, Director: Advanced Pediatric Dermatology. American Academy of Dermatology 70 th Annual Meeting. San Diego, CA. March 16-20, Speaker, Vascular Birthmarks Management Pearls. American Academy of Dermatology 70 th Annual Meeting. San Diego, CA. March 16-20, Speaker, Management of Complex Vascular Lesions. American Academy of Dermatology 70 th Annual Meeting. San Diego, CA. March 16-20, Speaker, Fun with Fungi and Other Infections. Pediatric Dermatology for the Practitioner, Philadelphia, PA. April 20-21, Speaker, Bugs, Drugs, and Birthmarks. American Academy of Dermatology Summer Meeting. Boston, MA. August 15-19, Speaker, What s New and Important in Pediatric Dermatology. Fall Clinical Dermatology Conference. Las Vegas, NV. October 4-7, Speaker, The Challenging Pediatric Eczema Patient. Fall Clinical Dermatology Conference. Las Vegas, NV. October 4-7, Speaker, How I Approach Atopic Dermatitis. Physician and Nurses Dermatology Symposium, Hyatt Long Beach Hotel. Long Beach, CA. October 12-13, Speaker, How I Approach Lumps and Bumps in Kids. Physician and Nurses Dermatology Symposium, Hyatt Long Beach Hotel. Long Beach, CA. October 12-13, Speaker, Peds Derm Bootcamp: Cases 101. Women s and Pediatric Dermatology Seminar. Grand Hyatt. San Francisco, CA. October 19-21, Speaker, Atopic Dermatitis: A Stepwide Approach. Women s and Pediatric Dermatology Seminar. Grand Hyatt. San Francisco, CA. October 19-21, Speaker, Case Solved! Dermpath to the Rescue. Women s and Pediatric Dermatology Seminar. Grand Hyatt. San Francisco, CA. October 19-21, Speaker, Lumps and Bumps in Little Ones: When to Worry, What to Do. Aloha Update: Pediatrics. Grand Hyatt Kauai Resort and Spa. Kauai, HI. October 27-November 2, Speaker, Acne Boot Camp : A How To for Pediatricians. Aloha Update: Pediatrics. Grand Hyatt Kauai Resort and Spa. Kauai, HI. October 27-November 2, Speaker, The Itch That Must Be Scratched: An Update of Pediatric Eczema. Aloha Update: Pediatrics. Grand Hyatt Kauai Resort and Spa. Kauai, HI. October 27-November 2, Speaker, Pediatric Infestations: Itchy Critters Head to Toe. Aloha Update: Pediatrics. Grand Hyatt Kauai Resort and Spa. Kauai, HI. October 27-November 2, Speaker, Moles and Melanoma: Pediatric Issues. Aloha Update: Pediatrics. Grand Hyatt Kauai Resort and Spa. Kauai, HI. October 27-November 2, Speaker, Infectious Pearls, Pediatric Slant: What is This? School Health Leadership Conference. Del Mar, CA. November 3, Speaker, Infectious Disease Update: What You Need to Know in the War on Bacteria, Viruses, Fungi, Parasites and Insects. ACMD NP and PA, Advances and Approaches for the Dermatological Practitioner. Grand Wailea Resort, Maui, HI. January 16-18, Speaker, Lunch with the Faculty, Pediatric Dermatology: Challenging Cases in Pediatric Dermatology. ACMD NP and PA, Advances and Approaches for the Dermatological Practitioner. Grand Wailea Resort, Maui, HI. January 16-18, Speaker, Lunch with the Faculty, Outside the Box Acne and Rosacea: Challenging Cases That Put Our Faculty to the Test. ACMD NP and PA, Advances and Approaches for the Dermatological Practitioner. Grand Wailea Resort, Maui, HI. January 16-18, Speaker, Pediatric Dermatology. Maui Derm: Advances in Cosmetic and Medical Dermatology. Grand Wailea Resort, Maui, HI. January 19-23, Speaker, Seeing Red? Vascular Lesion Update. SDEF 37 th Hawaii Dermatology Seminar. Grand Wailea Resort, Maui, HI. February 10-15, Speaker, What Else is New in Pediatric Dermatology? Lasers and Other Stuff. SDEF 37th Hawaii Dermatology Seminar. Grand Wailea Resort, Maui, HI. February 10-15, Speaker, Common Pediatric Skin Infections. 71 st Annual American Academy of Dermatology Meeting. Miami Beach, FL. March 1-5, Speaker, Session Moderator. Pediatric Dermatology for the Practitioner. San Diego, CA. April 5-6, Speaker Advanced Workshop: Dermpath to the Rescue Insight Into Challenging Cases. Pediatric Dermatology for the Practitioner. San Diego, CA. April 5-6, Speaker, Vascular Lesions in Kids: Breakthrough in Diagnosis & Management. Pediatric Dermatology for the Practitioner. San Diego, CA. April 5-6, 2013 Wynnis L. Tom, MD NIH Career Development K Award, 2011 UCSD Division of Dermatology, The Robert W. Goltz, MD, Excellence in Teaching Award, 2011 Session Director, American Academy of Dermatology Annual Meeting, 2011 Atopic Dermatitis Delphi Consensus Conference , Editorial Director Appointed, American Academy of Dermatology, Atopic Dermatology Guidelines Task Force Appointed, Junior Faculty Committee for the Society for Pediatric Dermatology Speaker, The Skin and Its Clues to Inherited and Other Syndromes. Grand Rounds, Department, Scripps Mercy Hospital. San Diego, CA. July 7, 2011 Speaker, Infantile Hemangiomas (When to Worry and What to Do). Clinical Conference, Division of Pediatric Otolaryngology, UCSD/Rady Children s Hospital. San Diego, CA. November 18, 2011 Speaker, Is it Growing or Gruesome? Non-Vascular Birthmarks and Other Lesions. Skin Disease Education Foundation 36th Hawaii Dermatology Seminar. Big Island, HI. February 2012 Speaker, Atopic Dermatitis Update. Skin Disease Education Foundation 36th Hawaii Dermatology Seminar. Big Island, HI. February 2012 Speaker, Derm Exam Prep Course: Pediatric Dermatology. American Academy of Dermatology 70th Annual Meeting. San Diego, CA. March 2012 Speaker, Atopic Dermatitis: Systemic Therapy Update. American Academy of Dermatology 70th Annual Meeting. San Diego, CA. March 2012 Speaker, Approaches to the Severe Atopic Child. American Academy of Dermatology 70th Annual Meeting. San Diego, CA. March 2012 Speaker, Cardiovascular Issues for the Pediderm. American Academy of Dermatology 70th Annual Meeting. San Diego, CA. March 2012 Speaker, Treatment of Atopic Dermatitis: How Do We Better Help the Red and Itch? Grand Rounds, Department, University of California, San Diego. San Diego, CA. April 6, Speaker, The Severe Atopic Child: How to Stop the Red and Itch? American Academy of Dermatology 71st Annual Meeting. Miami, FL. March Speaker, The Heartbreak of Psoriasis Literally. Pediatric Dermatology for the Practitioner Meeting. San Diego, CA. April Speaker, When Creams Are Not Enough: Systemic Therapies for Severe Eczema. Pediatric Dermatology for the Practitioner Meeting. San Diego, CA. April 2013 Andrew C. Krakowski, M.D. Pedatric Acne Guidelines Study Group; American Acne and Rosacea Society 2011-present Leadership Forum, American Academy of Dermatology CableFAX Best of the Web Awards; Honorable Mention for Original Content; boondocs Show, 2011 Co-Director, 22 nd Annual Pediatric Dermatology for the Practitioner CME Meeting, Rady Children's Hospital, San Diego, 2013 Academic Dermatology Leadership Program (ADLP), American Academy of Dermatology, 2012-present Speaker, Tall, dark, and melanoma? UCSD Occupational Health Annual Symposium, San Diego, CA, June Speaker, RASA1 (RAS p21 protein activator 1) mutation in a 13-year-old male. San Diego Dermatology Society, San Diego, CA, November 2011 Speaker, Lasers and photomedicine. University of California, San Diego, Division of Dermatology, San Diego, CA, December 14, 2011 Speaker, Rashes in the athlete. Pediatric and Adolescent Sports Medicine Program, San Diego, CA, March 1, 2012 Speaker, Sports dermatoses: What s that rash you re sporting? Annual Meeting of the American Academy of Dermatology (AAD), San Diego, CA, March 19, 2012 Speaker, The non-traditional physician s role in today s world of medicine. Penn Med Alumni Association. University of Pennsylvania, Philadelphia, PA, March 29, 2012 Speaker, Pediatric laser scar revision: A proposed new model of excellence. Rancho Bernardo Unit of the Auxiliary. Rady Children s Hospital, San Diego, San Diego, CA, April 18, 2012 Moderator; Grand Rounds. University of California, San Diego, Division of Dermatology, San Diego, CA, May 3, 2012 Speaker, Pediatric laser scar revision: A proposed new model of excellence. Del Cerro Unit of the Auxiliary. Rady Children s Hospital, San Diego, San Diego, CA, June 4, 2012 Speaker, What you really need to know for the boards. Real World Dermatology for Residents What You Really Need to Know, Las Vegas, NV, June 10, 2012 Speaker, Update on warts and molluscum. CPCMG Educational Meeting. San Diego, CA, June 12, 2012 Speaker, Update on procedural pediatric dermatology: Pediatric scar revision. Annual Summer Meeting of the American Academy of Dermatology (AAD), Boston, MA, August 17, 2012 Speaker, Fall Fantasy: Introduction to the Scar Treatment and Revision (S.T.A.R.) Program. Del Cerro Unit of the Auxiliary. Rady Children s Hospital, San Diego, San Diego, CA, September 29, 2012 Speaker, Pemphigus vulgaris: 7-year-old male with mouth sores, fissured tongue, and pain and redness of his gums. San Diego Dermatology Society, San Diego, CA, November 2012 Speaker, Basal cell nevus syndrome: 6-year-old male with cleft lip/ palate, macrocephaly, polysyndactyly and palmar/plantar pits. San Diego Dermatology Society, San Diego, CA, November 2012 Speaker, Suspected DOCK8 deficiency: 20-month-old male with severe eczema, antibody deficiency, recurrent pneumonias, and verruca vulgaris. San Diego Dermatology Society, San Diego, CA, November 2012 Speaker, Lipoid proteinosis: 3-year-old male with hoarseness, varioliform scarring, and string of pearls papules on bilateral superior eyelids. San Diego Dermatology Society, San Diego, CA, November 2012 Speaker, Wilderness & travel dermatology: A good vacation spoiled. 37 th Hawaii Dermatology Seminar, February 2013 Speaker, Pediatric procedural dermatology: Doc, will there be a scar? 37 th Hawaii Dermatology Seminar, Maui, HI, February 2013 Speaker, Hands-on workshop: Pediatric procedures in the office. 22 nd Annual Pediatric Dermatology for the Practitioner, San Diego, CA, April 4, 2013 Speaker, Pediatric scar revision. 22 nd Annual Pediatric Dermatology for the Practitioner, San Diego, CA, April 4, 2013 Speaker, Is this gonna be on the test? Pediatric board review. 22 nd Annual Pediatric Dermatology for the Practitioner, San Diego, CA, April 4, 2013 Speaker, Acne diagnosis and treatment: A fresh perspective. Pri- Med West 2013, Anaheim, CA, May 4, 2013 Speaker, Use of laser treatment for scarring and contractures San Diego Hand Therapy Special Interest Group, San Diego, CA, May 14, 2013 RESEARCH SUPPORT Lawrence F. Eichenfield, MD A Randomized, Double-Blind, Placebo-Controlled, Parallel- Group, Dose-Ranging Study Investigating the Efficacy, Safety, Pharmacokinetic and Biomarker Profiles of REGN668 Administered to Adult Patients with Moderate-to-Severe Atopic Dermatitis [R668- AD-1021] Regeneron Pharmaceuticals, Inc. $88,888 Apr present A Multicenter, Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Evaluation of Twice Daily PDI % in Comparison to PDI % in the Treatment of Mild to Moderate Atopic Dermatitis in Subjects 3 Months to Less Than 18 Years of Age [Protocol ] Precision Dermatology Inc $53, 572 Mar present Pharmacokinetics and pharmacodynamics of calcitriol 3 mcg/g ointment applied twice daily for 14 days under conditions of maximal use in pediatric subjects (2 to 12 years of age) with plaque psoriasis [RD.06.SPR.18104] Galderma $18,730 Feb present A Pharmacokinetic study of CD5789 followingdermal application of CD µg/g or 100 µg/g Cream under maximal use conditions 60 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 61

32 in subjects 9 to 17 years of age with Acne Vulgaris [RD.06. SPR.18237] Galderma $41,746 Nov present Clinical Evaluation of T.R.U.E. TEST Panel 3.2 in Children and Adolescents (PREA II) SmartPractice $71,454 Oct present A Multicenter, Prospective, Randomized, Open-label, Intra-subject Controlled Study of the Efficacy and Safety of ABH001 for the Treatment of Stalled Chronic Cutaneous Wounds Associated with Generalized Epidermolysis Bullosa [Protocol EB01-ABH001] Shire Regenerative Medicine $34,500 Sept present A randomized, multi-center, Investigator-blind, vehicle- and activecontrolled, phase 2 study to assess the efficacy and safety of different concentrations of CD5789 cream applied once daily in subjects with moderate to severe acne vulgaris [RD.06.SPR.18223] Galderma $107,950 June 2012-present A Phase 1, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Calcipotriene Foam, 0.005%, Applied Under Maximal-Use Conditions in Adolescent Subjects (Ages 12 to 16 Years) with Plaque Psoriasis [Clinical Study Protocol: STF ] Stiefel GlaxoSmithKline $58,000 Feb present An Open-Label Extension Study to Evaluate the Safety of Etanerceptin Pediatric Subjects with Plaque Psoriasis /Amgen $106,793 $251,799 Jan Present A Phase Two Study Evaluating the Safety and Efficacy of Once Daily Use of the LEO topical Suspension Containing Calcipotriol 50 mcg/g Plus Betamet MBL 0801/Leo Pharmaceutical Products Ltd. $70,279 $158,582 May 2010-Jan A Multi-Center, Double-Blinded, Vehicle Controlled, Phase 2 Study of JNJ AAA for the Treatment of Acne Vulgaris CA-P- 8023/Johnson & Johnson $100,685 $148,997 Jan Sept A Phase 2, Single-Arm Study to Evaluate the Safety and Pharmacokinetics of Alefacept in Adolescent Subjects with Moderate to Severe Psoriasis 0485-CL-0004/Astellas Pharma Inc. $77,278 $142,472 Feb Present Cross-Sectional Evaluation of Biological Markers of Cardiovascular Disease in Children and Adolescents with Psoriasis /Amgen $105,952 $133,500 Jan Oct A Randomized, Double-Blind, Placebo-Controlled, Dose Response Study for the Safety and Efficacy of Thymosin Beta 4 in the Treatment of Patients with Epidermolysis Bullosa SSEB/Regenerx Biopharmaceuticals, Inc. $90,065 $103,680 Dec Sep Evaluation of the Cutaneous Innate Immune and Clinical Response to Oral and Topical Vitamin D UCSD/CSSD/RCHSD Intramural Grant $50,000 Aug June 2011 Sheila Fallon Friedlander, MD Topical timolol for the treatment of infantile hemangiomas Valeant Pharmaceuticals $105, 750 Mar present A Randomized, Controlled, Multi-Dose, Multi-Center, Adaptive Phase II/III Study in Infants with Proliferating Infantile Hemangiomas Requiring Systemic Therapy to Compare Four Regimens of Propranolol to Placebo V0400 SB/Pierre Fabre Dermatologie $194,795 $245,442 Jan Present Autologous Retinal Pigmented Epithelial Cells Derived from Induced Pluripotent Stem Cells for the Treatment of Atrophic Age Related Macular Degeneration SUB CIRM/Scripps Research Institute $50,000 $60,000 Oct Sept Wynnis L. Tom, MD An Open-Label, Maximal Use, Systemic Exposure Study to Assess the Safety and Pharmacokinetic Profile of AN2728 Topical Ointment, 2% in Children and Adolescents with Atopic Dermatitis [Protocol AN2728-AD-102] Anacor Pharmaceuticals $46, 150 June 2013 present A Phase 3 Study to Evaluate the Efficacy, Safety, and Effect of Withdrawal and Retreatment With Brodalumab in Subjects With Moderate to Severe Plaque Psoriasis: AMAGINE-1 [Protocol ] Amgen $126,000 May 2012 present An Open-Label Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of AN2728 Ointment in Adolescents with Atopic Dermatitis [AN2728-AD-203] Anacor Pharmaceuticals $56,031 May 2012 Feb Genetic Influence in Pediatric Psoriasis 1 K23 AR A1/NIH (NIAMS) $122,500 $661,500 July June 2016 Impact of the Severity of Pediatric Psoriasis in Childhood Body Mass Index and Co-Morbid Risk Factors: An Epidemiologic Analysis /International Psoriasis Council $9,524 $12,000 Apr Mar Andrew Krakowski, MD Collection of skin biopsy samples from subjects with Recessive Dystrophic Epidermolysis Bullosa for the evaluation of a new genetically modified fibroblast cell therapy product candidate Fibrocell Sciences, Inc $13,080 Mar present Double-Blind, Prospective, Randomized, Vehicle Controlled Multi-Center Study of hotodynamic Therapy with Visionac Cream in Patients with Acne Vulgaris PC TA 206/11/Photocure ASA (Norway) $54,841 $ 69,100 Apr Jun 2012 A Multi-Center Randomized Vehicle Controlled Double-Blind Study to Evaluate the Safety and Efficacy of Epiduo Gel 0.1% /2.5% Administered Once Daily 18155/Galderma Laboratory, Inc. $53,244 $67,088 July Oct Safety and efficacy of TACLONEX ointment ("Study Drug") in adolescent patients (aged 12 to17 years) with psoriasis vulgaris MCB 0501 INT/Leo Pharmaceutical Products Ltd. $51,510 $51,510 May May UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 63

33 Dysmorphology & Teratology 64 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 65

34 INTRODUCTION The Division of Dysmorphology and Teratology is dedicated to providing comprehensive specialized care in the diagnosis, treatment, and management of birth defects and other adverse pregnancy outcomes. Through clinical, epidemiological, and basic science research, the scientific goals of the Division are: 1) to better understand the etiology and developmental pathogenesis of birth defects and other adverse pregnancy outcomes due to environmental exposures; 2) to develop interventions and diagnostic modalities to prevent those birth defects; and 3) to educate healthcare providers the general public about teratogenic exposures. FACULTY Led by Dr. Kenneth Lyons Jones, a pediatrician and dysmorphologist-teratologist, and Dr. Christina Chambers, a perinatal epidemiologist and teratologist, the Division of Dysmorphology and Teratology currently runs the State of California Birth Defects Monitoring Program, a long-standing public health surveillance program for birth defects that monitors 15 counties in California and is linked to a State biorepository for maternal serum samples and infant blood spots; has partnered with the newly founded Rady Genomic and Systems Medicine Institute to develop a program for better understanding the genetic underpinnings of some birth defects; established a research only Human Milk Biorepository; and collaborates with institutions and researchers both domestically (including Boston University, Stanford University, University of Washington, University of New Mexico, Emory University, Indiana University, University of South Florida) and internationally (Canada, Australia, South Africa, Ukraine, South Korea, Poland and Mexico). In , the Division employed over 70 clinical and research staff, had $27,760,070 in total funding, and published 56 manuscripts, 6 book chapters and 1 book. In 2015, the Division expanded its faculty with the addition of Miguel del Campo, MD, PhD, a medical geneticist and a leader in the fields of clinical genetics and dysmorphology. Other key additions in the last two years include Wladimir Wertelecki, MD, Project Scientist, with expertise in medical genetics, and the research liaison for our collaboration with the Omni-Net for Children foundation in Ukraine; Kristin Palmsten, ScD, Assistant Project Scientist, specializing in pharmacoepidemiology and perinatal epidemiology; Diana R. Simmes, MPH, Academic Coordinator, the Institute for Fetal Alcohol Spectrum Disorders Discovery; and Jennifer Zellner, PhD, Director of Communications and Research Development. Another major development for the Division of Dysmorphology and Teratology over the past two years was the rebranding of its public-facing center, now called the Center for Better Beginnings (formally known as the Center for the Promotion of Maternal Health and Infant Development). This re-brand recognizes the importance of translating and promoting our clinical, research, and service activities to non-academic and non-medical audiences. The Center continues to expand and is now one of North America s foremost institutes for breakthrough research and education in maternal health and child development and brings together experts from all over the world to promote healthy pregnancies and prevent adverse outcomes associated with exposures during pregnancy and lactation. Through patient care, teaching, advocacy and research, the Center serves as a trusted resource for agencies, organizations, and individuals on exposures during pregnancy and lactation. Kenneth Lyons Jones, MD Distinguished Professor ; Co-Director, Center for Better Beginnings; Division Chief Christina Chambers, PhD, MPH Professor, Vice Chair of Clinical Research, Director, Center for Better Beginnings; Professor of Epidemiology & Global Health, Dept. of Family Medicine & Public Health; Clinical Professor, Skaggs School of Pharmacy & Pharmaceutical Sciences; Associate Director, Clinical Translational Research Institute Miguel del Campo, MD, PhD Associate Clinical Professor Medical and research training continues to be a priority for the Division of Dysmorphology and Teratology. Over the past two years, the Division has created a Stats/Epi Seminar Series and a Clinical Research Seminar Series for researchers in the Department and at Rady Children s Hospital-San Diego, and has also organized and hosted an international continuing medical education course on Pregnancy and Lactation in Women with Autoimmune Diseases. Division members train and mentor high school, undergraduate, graduate, and medical students, fellows, post-doctoral scholars, visiting scholars, and other medical and research professionals. Additionally, the Division remains at the forefront both nationally and internationally in the field of Fetal Alcohol Spectrum Disorders (FASD). Advances include the award of a 4 year grant from the CDC to train pediatricians and nurses in the prevention of alcohol-exposed pregnancies; the development of a telemedicine program whereby a long-distance evaluation of a child for FASD can be conducted; the launching of nurse conducted FASD screenings; and creating the SoCal NOFAS website and a local bilingual support group for families affected by FASD. 66 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report DIVISION FAST FACTS $10 Million in Major Research Grants MAJOR PLANS AND GOALS Expand and solidify sustainable federal funding for teratogen counseling services in California and nationwide Further develop the Institute for Fetal Alcohol Spectrum Disorders Discovery to serve patients and provide sustainable services and research opportunities Expand the reach of Mommy's Milk Human Milk Research Biorepository with new collaborations and national sample collections Establish the San Diego study of Mothers and Infants (SOMI) platform to test and generate hypotheses about genetics and environment as related to child health outcomes in our community. Kristin Palmsten, ScD Assistant Project Scientist Annika Montag, PhD INPATIENT/OUTPATIENT The Division of Dysmorphology and Teratology has a number of clinical activities providing diagnostic services, genetic and teratogen counseling, and long-term follow-up of children with birth defects nationally and internationally. Clinics continue to be held in San Diego, CA and Tijuana, Mexico. Inpatient consults are conducted at UCSD Medical Center (in the neonatal intensive care unit, newborn nursery and autopsy service) and at Scripps Mercy Hospital. Outpatient consults and follow-up take place at Rady Children s Hospital San Diego and at Hospital del Infantil de las Californias in Tijuana. Additionally, through our free teratogen information service, MotherToBaby California, the Division continues to provide information to pregnant and breastfeeding women, women planning pregnancy, fathers, family members, physicians, and other health care providers worldwide about exposures during pregnancy and lactation including but not limited to: Over-the-Counter Medications Prescription Medications Vitamins/Supplements Herbal Supplements Alcohol/Recreational Drugs Vaccinations or FELLOWS Wladimir Wertelecki, MD Project Scientist CLINICAL ACTIVITIES Immunizations Diseases or Infections Chemicals Pesticides Occupational Exposures Environmental Exposures Paternal Exposures Gretchen Bandoli, PhD Additionally, the Division of Dysmorphology and Teratology houses the Institute for Fetal Alcohol Spectrum Disorders Discovery (IFASDD), which provides diagnostic, screening, and intervention services to children with prenatal alcohol exposure. Services include dysmorphology exams, the Math Interactive Learning Experience (MILE) intervention program, educational support, a parent support group that meets monthly, an FASD patient registry, and a significant community outreach and education program. Nurse conducted FASD screenings are provided to high-risk populations in early intervention programs and the juvenile justice system. IFASDD works closely with the Southern California affiliate of the National Organization on Fetal Alcohol Syndrome (SoCal NOFAS) to provide support to families, increase public awareness of FASD through a speakers bureau, and promote the prevention of alcohol-exposed pregnancies. With funding from the National Institute on Alcohol Abuse and Alcoholism, the Division is developing a telemedicine program that will allow expert dysmorphologists to evaluate children in remote locations for FASDs. This will provide an innovative approach to the diagnosis of FASD in underserved areas throughout the world where physicians with expertise in diagnosis of this disorder are unavailable. This system will initially be field-tested in San Diego and then will be expanded worldwide Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 67

35 The Division offers a wide range of teaching and training activities through clinical rotations, educational courses, pre- and postdoctoral training programs, Clinical Research Seminars, Stat/Epi Seminars, Journal Club, continuing medical education events, and community outreach. Kenneth Lyons Jones, MD Dr. Jones conducts resident rounds for neonatal fellows, residents and medical students in the UCSD neonatal intensive care unit and newborn nursery and gives didactic lectures at the UCSD School of Medicine. He has a weekly one and one-half day outpatient clinic at Rady Children s Hospital-San Diego in which at least one UCSD Pediatric Resident is directly involved. Fourth-year medical students may also rotate on this service on a case-by-case basis. Christina D. Chambers, PhD, MPH Dr. Chambers continues to teach Human Teratology, an elective course offered in the Skaggs School of Pharmacy and Pharmaceutical Sciences (SPPS 261). This course is open to pharmacy students and students in other health sciences. Additionally, she conducts six-week elective rotations in teratology for four to eight UCSD pharmacy students. She continues to chair or serve as a committee member for medical students as part of the ISP and continues to mentor NIH summer internship projects for medical and pharmacy students. In her role as the Associate Director of the Clinical Translational Research Institute at UCSD, Dr. Chambers teaches on the topic of reproductive epidemiology as part of the CREST program at UCSD and is in the process of developing a CREST course on Lifecourse Through the Center for Better Beginnings, the Division of Dysmorphology and Teratology continues to conduct cutting-edge local, national and international epidemiologic and biomedical research focused on the identification and prevention of birth defects, miscarriage, preterm birth, pre and post-natal growth abnormalities and longer term neurodevelopmental and functional impairments. This research has been instrumental in identifying previously unrecognized human teratogens, as well as ruling out substantial risk for other medications and vaccines, and has led to changes in clinical practice and public health policy. The specific research areas and highlights in the Division include: 1. Birth Defects Etiology and Prevention In 2013, Dr. Chambers took on the PI role for a three-year contract to run the State of California Birth Defects Monitoring Program, a long-standing public health surveillance program for birth defects that monitors 15 counties in California and is linked to a State biorepository for maternal serum samples and infant blood spots. Additionally, collaborations have been established with CDC s SMART collaborative program to evaluate assisted reproductive technology birth outcomes in California; the Department of Medicine to evaluate a metabolomics signature in children with specific types of heart defects; and with researchers state wide to study the etiology of gastroschisis. 2. Medications and Vaccines in Pregnancy The Division of Dysmorphology and Teratology continues to be the coordinating center for the MotherToBaby Pregnancy Studies, which consist of multiple national post-marketing surveillance studies of medication and vaccine safety in pregnancy. These studies are conducted through the Organization of Teratology Information Specialists. Our Division provides the research infrastructure that allows for proper study design, subject ascertainment, follow-up, 68 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report TEACHING ACTIVITIES Epidemiology. Furthermore, she teaches in Clinical Epidemiology and Perinatal Epidemiology elective courses offered to graduate students at UCSD, and has lectured on maternal child health in master s level courses in the School of Public Health at San Diego State University. These lectures have focused on various obstetric and pediatric diseases, approaches to conducting research on these topics, and prevention. Dr. Chambers has a strong history of supporting graduate students, postdoctoral fellows and junior faculty in epidemiologic methods and in career development. Over the past two years, she has been the primary mentor for 4 pre-doctoral students, 5 post-doctoral scholars, 3 K-Award fellows, and 3 visiting scholars. Dr. Chambers has provided support for maximizing research independence, professional development, and career success through the expansion of leadership opportunities, promotion of professional visibility and fellowship opportunities. Miguel del Campo, MD, PhD Dr. del Campo teaches medical students and residents how to diagnose and care for children born with birth defects. Teaching takes place at the bedside and in the classroom. He has expertise and experience with FASD; mechanisms of normal and abnormal structural development, particularly through the use of new genetic technologies; and he has had substantial involvement in establishing the safety of prenatal exposures to medications and vaccines. RESEARCH ACTIVITIES collection of data, statistical analysis and interpretation of data. Some of these studies are done in collaboration with the American Academy of Allergy Asthma and Immunology and Boston University as part of the Vaccines and Medications in Pregnancy Surveillance System. Our ongoing studies on medications and vaccines in pregnancy include: Medications used to treat autoimmune diseases such as ulcerative colitis and Crohn's Disease, Rheumatoid Arthritis, Psoriasis, Psoriatic Arthritis, Ankylosing Spondylitis, and Multiple Sclerosis The Seasonal Flu Vaccine The Pertussis Vaccine Medications used to treat Asthma 3. Fetal Alcohol Spectrum Disorders Research efforts in the area of FASDs continue to be a strong focus in the Division. Our FASD research is conducted locally, nationally and internationally and centers on: estimating the prevalence of FASD; establishing an FASD Patient Research Registry; examining a variety of risk factors for FASD; cross-cultural comparisons of the dysmorphic features of children exposed to alcohol; testing intervention strategies to reduce risky alcohol consumption among women of reproductive age; and biomarker development. For example, in 2014 the Division established a collaboration with Texas A&M University to develop mirna biomarkers of maternal alcohol exposures and with researchers and FASD specialist at the Child Development Center in Queensland, Australia. 4. Research Only Human Milk Biorepository In collaboration with UCSD's Clinical and Translational Research Institute, Rady Children s Hospital-San Diego, Sharp Mary Birch Hospital for Women and Newborns and San Diego State University's School of Public Health, in 2014 we opened the Mommy's Milk Human Milk Research Biorepository. This will enable scientists from diverse fields to answer a multitude of questions about human milk, including its unique biochemical properties and the extent to which pharmaceuticals and substances to which nursing mothers are exposed can be passed to the infant during breastfeeding and their effects on the infant both while nursing and long term. RESEARCH SUPPORT Christina D. Chambers, PhD, MPH OPP /15/ /14/2016 $49,580 Bill & Melinda Gates Foundation Gestational Dating at Birth by Metabolic Profile Sub-award # /25/ /24/2019 $3,297,800 Celgene Apremlist Pregnancy Exposure Registry: OTIS Autoimmune Diseases in Pregnancy Project U261IHS /01/ /31/2018 $234,906 NIH/HIGM/IHC NARCH VII Development of a Model Resource and Support Network for FASD-Affected Families in Tribal and Urban Native American Communities /01/ /31/2017 $1,491,036 AAAAI VAMPSS Postmarketing Surveillance of Afluria Safety in Pregnancy /17/ /16/2018 $3,708,451 Pfizer Tofacitinib Pregnancy Exposure Registry OTIS Autoimmune Diseases in Pregnancy Project /01/ /31/2020 $2,340,937 Janssen Biotech, Inc 04/01/ /31/2016 $4,889,207 California Department of Health California Birth Defects Monitoring Program R01 AA /10/ /31/2017 $953,100 NIH/NIAAA Influence of Nutrition on Growth and Neurodevelopment in Children with FASD in Ukraine /13/ /12/2017 $4,309,781 UCB Pharma, Inc. Cimzia Pregnancy Exposure Registry an OTIS Autoimmune Diseases in Pregnancy Project /25/ /31/2017 $2,530,817 Genzyme (Sanofi-Aventis) The Teriflunomide Pregnancy Exposure Registry an OTIS Autoimmune Diseases in Pregnancy Project /01/ /31/2016 $3,417,966 Hoffman La Roche Genentech OTIS Autoimmune Diseases in Pregnancy Project: The Actemra Pregnancy Registry U01AA /20/ /31/2016 $9,946,558 NIH-NIAAA Co-FASP Measurement of Prevalence of FASD in San Diego County /01/ /01/2016 $3,152,027 Bristol Myers/Squibb OTIS Autoimmune Diseases in Pregnancy Project; The Abatacept Pregnancy Registry 07/18/ /31/2016 $2,532,920 Apotex, Inc., Barr Laboratories, Inc. TEVA Pharmaceuticals, USA, Kali Laboratories, Sandoz Pharmaceuticals Prospective Follow-Up of Pregnancy Exposure to Leflunomide--an OTIS Autoimmune Diseases in Pregnancy Project U01AA /30/ /31/2017 $7,568,350 NIH/NIAAA Early Identification of Affected Children and Risk Factors for FASD in Ukraine /28/2014-1/26/2015 $65,000 AAAAI Duloxetine Pregnancy Exposure Registry /15/ /14/2014 $149,371 Glaxo Smith Kline Asthma Control Test (ACT) Pregnancy Study A VAMPSS Study /12/ /30/2014 $1,852,788 Novartis Menveo Vaccine Pregnancy Registry A VAMPSS Study HHSO C 02/25/ /27/2015 $4,290,651 DHHS BARDA H1N1 and Influenza Vaccines and Antiviral Medications in Pregnancy (VAMPSS) U26IHS HIS 09/01/ /31/2014 $91,570 NIH/NIGM/IHC NARCH - Native American Screening, Brief Intervention, and Referral for Treatment (NASBIRT) For Prevention of Alcohol Use in Pregnancy in San Diego County R18HS /30/ /31/2015 $2,410,401 PHS (AHRQ) Agency for Healthcare Research and Quality Pregnancy Outcomes and Asthma Medications in Pregnancy: a Demonstration Project CTA# /01/ /19/2014 $6,182,355 Immunex Corporation/Amgen Incorporated Rheumatic Diseases and Psoriasis Pregnancy Registry--OTIS Autoimmune Diseases in Pregnancy Project Kenneth Lyons Jones, MD Continuous $330,774 Community Service Project State of California Department of Education: California Teratogen Information Service & Clinical Research Program Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 69

36 U01DD /30/ /29/2018 $1,100,000 Center for Disease Control (CDC) FASD Prevention, Identification, and Treatment: Trainings and Education for Healthcare Providers by the Western PIC 2U24AA /30/ /31/2017 $2,653,172 NIH/NIAAA Dysmorphology Core /01/ /12/2015 $3,830,319 AbbVie Laboratories (Abbott) Prospective Follow-up of Pregnancy Exposure to Humira (adalimumab) PUBLICATIONS Coles CD, Kable JA, Keen CL, Jones KL, Wertelecki W, Granovska IV, Pashtepa AO, Chambers CD; CIFASD. Dose and timing of prenatal alcohol exposure and maternal nutritional supplements: Developmental effects on 6-Month-Old Infants. Matern Child Health J 2015;19:2605:2614. Karam F, Sheehy O, Huneau MC, Chambers C, Fraser WD, Johnson D, Kao K, Martin BZ, Riordan SH, Roth M, St-André M, Lavigne SV, Wolfe L, Bérard A. The ASQ and R-PDQ telephone-administered validation within the OTIS Antidepressant in Pregnancy Study. Psychol Assess 2015;27: Chambers C. Over-the-counter medications: Risk and safety in pregnancy. Semin Perinatol 2015;39: Baril L, Rosillon D, Willame C, Angelo MG, Zima J, van den Bosch JH, Van Staa T, Boggon R, Bunge EM, Hernandez-Diaz S, Chambers CD. Risk of spontaneous abortion and other pregnancy outcomes in year old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom. Vaccine 2015;33: Migliorini R, Moore EM, Glass L, Infante MA, Tapert SF, Jones KL, Mattson SN, Riley EP. Anterior cingulate cortex surface area relates to behavioral inhibition in adolescents with and without heavy prenatal alcohol exposure. Behav Brain Res 2015;292: Kable JA, Coles CD, Keen CL, Uriu-Adams JY, Jones KL, Yevtushok L, Kulikovsky Y, Wertelecki W, Pedersen TL, Chambers CD; CIFASD. The impact of micronutrient supplementation in alcoholexposed pregnancies on information processing skills in Ukrainian infants. Alcohol 2015;49: Palmsten K, Hernández-Díaz S, Chambers CD, Mogun H, Lai S, Gilmer TP, Huybrechts KF. The most commonly dispensed prescription medications among pregnant women enrolled in the U.S. Medicaid program. Obstet Gynecol 2015;126: Alwan S, Chambers CD. Findings from the National Birth Defects Prevention Study: Interpretation and translation for the clinician. Birth Defects Res A Clin Mol Teratol 2015;103: Montag AC, Brodine SK, Alcaraz JE, Clapp JD, Allison MA, Calac DJ, Hull AD, Gorman JR, Jones KL, Chambers CD. Effect of depression on risky drinking and response to a Screening, Brief Intervention, and Referral to Treatment Intervention. Am J Public Health 2015;105: Mody SK, Wu J, Ornelas M, Kernahan C, Salas E, Kao K, Felix R, Chambers C. Using the electronic medical record to refer women taking category D or X medications for teratogen and contraceptive counseling. Birth Defects Res A Clin Mol Teratol 2015;103: Baer RJ, Chambers CD, Jones KL, Shew SB, MacKenzie TC, Shaw GM, Jelliffe-Pawlowski LL. Maternal factors associated with the occurrence of gastroschisis. Am J Med Genet A 2015;167: Mitchell AA, Louik C, Chambers C, Jones KL, Schatz M. Immunization surveillance systems for pregnant women. Pharmacoepidemiol Drug Saf 2015;24:669. Gautam P, Lebel C, Narr KL, Mattson SN, May PA, Adnams CM, Riley EP, Jones KL, Kan EC, Sowell ER. Volume changes and brainbehavior relationships in white matter and subcortical gray matter in children with prenatal alcohol exposure. Hum Brain Mapp 2015;36: Lu S, Du S, Ren Z, Zhao J, Chambers C, Wang J, Ma G. Accessibility of catering service venues and adolescent drinking in Beijing, China. Int J Environ Res Public Health 2015;12: Palmsten K, Chambers CD. Hypospadias: One defect, multiple causes, acting through shared pathways. Curr Epidemiol Rep 2015;2: Gorman JR, Chambers CD. Pregnant women s attitudes toward influenza vaccination while breastfeeding. Preventive Medicine Reports 2015;2: Hoyme HE, Hoyme DB, Elliott AJ, Blankenship J, Kalberg WO, Buckley D, Abdul-Rahman O, Adam MP, Robinson LK, Manning M, Bezuidenhout H, Jones KL, May PA. A South African mixed race lip/ philtrum guide for diagnosis of fetal alcohol spectrum disorders. Am J Med Genet A 2015;167A: Bharti B, Lee SJ, Lindsay SP, Wingard DL, Jones KL, Lemus H, Chambers CD. Disease severity and pregnancy outcomes in women with rheumatoid arthritis: Results from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project. J Rheumatol 2015;43: Kavanaugh A, Cush JJ, Ahmed MS, Bermas BL, Chakravarty E, Chambers C, Clowse M, Curtis JR, Dao K, Hankins GD, Koren G, Kim SC, Lapteva L, Mahadevan U, Moore T, Nolan M, Ren Z, Sammaritano LR, Seymour S, Weisman MH. Proceedings from the ACR Reproductive Health Summit: The management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res (Hoboken) 2015;67: Ware Al, Infante MA, O Briend JW, Tapert SF, Jones KL, Riley EP, Mattson SN. An fmri study of behavioral response inhibition in adolescents with and without histories of heavy prenatal alcohol exposure. Behav Brain Res 2015;278: Montag AC, Brodine SK, Alcaraz JE, Clapp JD, Allison MA, Calac DJ, Hull AD, Gorman JR, Jones KL, Chambers CD. Preventing alcohol-exposed pregnancy among American Indian/Alaska Native population: Effect of a screening, brief intervention, and referral to treatment intervention. Alcohol Clin Exp Res 2015;39: Alwan S, Chambers CD, Armenti VT, Sadovnick AD. The need for a disease-specific prospective pregnancy registry for multiple sclerosis (MS). Mult Scler Relat Disord 2015;4:6-17. Irvin VL, Hofstetter CR, Nichols JF, Chambers CD, Usita PM, Norman GJ, Kang S, Hovell MF. Compliance with smoke-free policies in Korean bars and restaurants in California: A descriptive analysis. Asian Pac J Cancer Prev 2015;16: Weber-Schoendorfer C, Chambers C, Wacker E, Beghin D, Bernaard N, on behalf of the network of French Pharmacovigilance centers, Shechtman S, Johnson D, Cuppers-Maarschalkerweerd B, Pistelli A, Clementi M, Winterfeld U, Elefant E, Koren G, Vial T, Ornory A, Meister R, Schaefer C. Pregnancy outcomes after rheumatologic methotrexate (MTX) treatment prior to or during early pregnancy: A prospective multicenter cohort study. Arthritis Rheumatol 2014;66: Smith EN, Jepsen K, Arias AD, Shepard PJ, Chambers CD, Frazer KA. Genetic ancestry of participants in the National Children s Study. Genome Biol 2014;15:R22. Chambers CD, Yevtushok L, Zymak-Zakutnya N, Korzhynskyy Y, Ostapchuk L, Akhmedzhanova D, Chan PR, Xu R, Wertelecki W. Prevalence and predictors of maternal alcohol consumption in 2 regions of Ukraine. Alcohol Clin Exp Res 2014;38: Xu R, Luo Y, Glynn R, Johnson D, Jones KL, Chambers C. Timedependent propensity score for assessing the effect of vaccine exposure on pregnancy outcomes through pregnancy exposure cohort studies. Int J Environ Res Public Health 2014;11: Popova S, Chambers CD. Fetal Alcohol Spectrum Disorders must be recognized globally as a large public health problem. Int J Alcohol Drug Res 2014;3:1-3. Broussard CS, Frey MT, Hernandez-Diaz S, Greene MF, Chambers CD, Sahin L, Collins Sharp BA, Honein MA. Developing a systematic approach to safer medication use during pregnancy: Summary of a Centers for Disease Control and Prevention-convened meeting. Am J Obstet Gynecol 2014;211: Namazy JA, Chambers C, Schatz M. Safety of therapeutic options for treating asthma in pregnancy. Expert Opin Drug Saf 2014;13: Østensen M, Andreoli L, Brucato A, Cetin I, Chambers C, Clowse ME, Costedoat-Chalumeau N, Cutolo M, Dolhain R, Fenstad MH, Förger F, Wahren-Herlenius M, Ruiz-Irastorza G, Koksvik H, Nelson-Piercy C, Shoenfeld Y, Tincani A, Villiger PM, Wallenius M, von Wolff M. State of the art: Reproduction and pregnancy in rheumatic diseases. Autoimmun Rev 2014;14: Gautam P, Nuñez SC, Narr KL, Mattson SN, May PA, Adnams CM, Riley EP, Jones KL, Kan EC, Sowell ER. Developmental trajectories for visuo-spatial attention are altered by prenatal alcohol exposure: A longitudinal FMRI study. Cereb Cortex 2015;25: Nguyen TT, Glass L, Coles CD, Kable JA, May PA, Kalberg WO, Sowell ER, Jones KL, Riley EP, Mattson SN; the CIFASD. The clinical utility and specificity of parent report of executive function among children with prenatal alcohol exposure. J Int Neuropsychol Soc 2014;20: Wang G, Murphy VE, Namzy J, Powell H, Schatz M, Chambers C, Attia J, Gibson PG. The risk of maternal and placental complications in pregnant women with asthma: A systematic review and metaanalysis. J Matern Fetal Neonatal Med 2014;27: Ware AL, Glass L, Crocker N, Deweese BN, Coles CD, Kable JA, May PA, Kalberg WO, Sowell ER, Jones KL, Riley EP, Mattson SN; CIFASD. Effects of prenatal alcohol exposure and attention-deficit/ hyperactivity disorder on adaptive functioning. Alcohol Clin Exp Res 2014;38: Glass L, Graham DM, Dewees BN, Jones KL, Riley EP, Mattson SN. Correspondence of parent report and laboratory measures of inattention and hyperactivity in children with heavy prenatal alcohol exposure. Neurotoxicol Teratol 2014;42: Tran B, Thomas AG, Vaida F, Ditsela M, Phetogo R, Kelapile D, Haubrich R, Chambers C, Schaffer R. An intervention study examining the effects of condom wrapper graphics and scent on condom use in the Botswana Defence Force. AIDS Care 2014;26: West JH, Blumberg EJ, Kelley NJ, Hill L, Sipan CL, Schmitz KE, Kolody B, Chambers CD, Friedman LS, Hovell MF. The role of parenting in alcohol and tobacco use among Latino adolescents. J Child Adolesc Subst Abuse 2013;22: Namazy JA, Murphy VE, Powell H, Gibson PG, Chambers CD, Schatz M. Effects of asthma severity, exacerbations, and oral corticosteroids on perinatal outcomes. Eur Respir J 2013;41: Louik C, Chambers CD, Jacobs D, Rice F, Johnson D, Mitchell A. Influenza vaccine safety in pregnancy: Can we identify exposures? Pharmacoepidemiol Drug Saf 2013;22: Jones KL, Weiss LA, Hagey LR, Gonzalez V, Benirschke K, Chambers CD. Altered lipid metabolism in gastroschisis: A novel hypothesis. Am J Med Genet A 2013;161A: Bracken MB, Baker D, Cauley JA, Chambers CD, Culhane J, Dabelea D, Dearborn D, Drews-Botsch CD, Dudley DJ, Durkin M, Entwisle B, Flick L, Hale D, Holl J, Hovell M, Hudak M, Paneth N, Specker B, Wilhelm M, Wyatt S. New models for large prospective studies: Is there a risk of throwing out the baby with the bathwater? Am J Epidemiol 2013;177: Ding D, Adams MA, Sallis JF, Norman GJ, Hovell MF, Chambers CD, Hofstetter CR, Bowles HR, Hagströmer M, Craig CL, Gomez LF, Bourdeaudhuij ID, Macfarlane DJ, Matsudo V, McLean G, Sjöstroöm M, Tomten H, Lefevre J, Volbekiene V, Bauman AE. Perceived neighborhood environment and physical activity in 11 countries: Do associations differ by country? Int J Behav Nutr Phys Act 2013;14:10:57. Kay VR, Chambers CD, Foster WG. Reproductive and developmental effects of phthalate diesters in females. Crit Rev Toxicology 2013;43: Murphy VE, Wang G, Namazy JA, Powell H, Gibson PG, Chambers C, Schatz M. The risk of congenital malformations, perinatal mortality, and neonatal hospitalization among pregnant women with asthma: A systemic review and meta-analysis. BJOG 2013;120: Gorman JR, Clapp JD, Calac D, Kolander C, Nyquist C, Chambers CD. Creating a culturally appropriate web-based behavioral intervention for American Indian/Alaska Native women in Southern California: The healthy women, healthy native women, healthy Native Nation study. Am Indian Alsk Native Ment Health Res 2013;20:1-15. Weiss LA, Chambers CD. Associations between multivitamin supplement use and alcohol consumption before pregnancy: Pregnancy risk assessment monitoring system, 2004 to Alcohol Clin Exp Res 2013;37: Chambers CD, Johnson D, Xu R, Luo Y, Louik C, Mitchell AA, Schatz M, Jones KL: OTIS Collaborative Research Group. Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: Birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants. Vaccine 2013;31: Glass L, Ware AL, Crocker N, Deweese BN, Coles CD, Kable JA, May PA, Kalberg WO, Sowell ER, Jones KL, Riley EP, Mattson SN; the CIFASD. Neuropsychological deficits associated with heavy prenatal alcohol exposure are not exacerbated by ADHD. Neuropsychology 2013;27: UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 71

37 O'Brien JW, Norman AL, Fryer SL, Tapert SF, Paulus MP, Jones KL, Riley EP, Mattson SN. Effect of predictive cuing on response inhibition in children with heavy prenatal alcohol exposure. Alcohol Clin Exp Res 2013;37: Ware AL, O Brien JW, Crocker N, Deweese BN, Roesch SC, Coles CD, Kable JA, May PA, Kalberg WO, Sowell ER, Jones KL, Riley EP, Mattson SN; the CIFASD. The effects of prenatal alcohol exposure and attention-deficit/hyperactivity disorder on psychopathology and behavior. Alcohol Clin Exp Res 2013;37: Louik C, Ahrens K, Kerr S, Pyo J, Chambers C, Jones, KL, Schatz M, Mitchell AA. Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: Exposure prevalence, preterm delivery, and specific birth defects. Vaccine 2013;31: Tran BR, Thomas AG, Ditsela M, Vaida F, Phetogo R, Kelapile D, Chambers C, Haubrich R, Shaffer R. Condom use behaviors and correlates of use in the Botswana Defence force. Int J STD AIDS 2013;24: Tran B, Thomas AG, Vaida F, Ditsela M, Phetogo R, Kelapile D, Chambers C, Haubrich R, Shaffer R. Comparisons of reported sexual behaviors from a retrospective survey versus a prospective diary in the Botswana Defence Force. AIDS Educ Prev 2013;25: Mattson SN, Roesch SC, Glass L, Deweese BN, Coles CD, Kable JA, May PA, Kalberg WO, Sowell ER, Adnams CM, Jones KL, Riley EP; the CIFASD. Further development of a neurobehavioral profile of fetal alcohol spectrum disorders. Alcohol Clin Exp Res 2013;37: Chambers CD, Andrews EB. Drug safety in pregnancy. In: Andrews EB, Moore N eds. Mann s Pharmacovigilance, 3rd Edition. Chichester, UK: John Wiley and Sons, Ltd.; 2014: Chambers C. Safe caffeine exposure levels in vulnerable populations: Pregnant women and infants. In: Caffeine in Food and Dietary Supplements: Examining Safety Workshop Summary. Washington, DC: Institute of Medicine of the National Academies Press, 2014: Schatz M, Zeiger RS, Falkoff R, Chambers C, Macy E, Mellon MH. Asthma and allergic diseases during pregnancy. In: Adkinson N, Bocher BS, Burks A, Busse WW, Holgate ST, Lemanske RE, O Henir RE, eds. Middleton s Allergy 2 Volume Set, 8th Edition. Philadelphia, PA: Elsevier Saunders; 2014: Chambers CD, the American Academy, American College of Obstetricians and Gynecologists. Neonatal Encephalopathy and Neurologic Outcome/the American College of Obstetricians and Gynecologists, American Academy, 2nd Edition. Elk Grove Village, IL: AAP, Washington, DC: American College of Obstetricians and Gynecologists 2014:e Chambers CD. Birth defects and the environment. In: Androgen PJ, Etzel RA, eds. Textbook of Children s Environmental Health. New York, NY: Oxford University Press; Chambers CD, Scialli A. Teratogenesis and environmental exposure. In: Creasy RK, Resnik R, Iams JD, eds. Creasy and Resnick s Maternal-Fetal Medicine: Principles and Practice,7th Edition. Philadelphia, PA: Elsevier Saunders; 2013; Jones KL, Jones MC, Del Campo M. Smith s Recognizable Patterns of Human Malformation, 7 th ed. Philadelphia, PA: Elsevier UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 73

38 Emergency Medicine 74 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 75

39 INTRODUCTION The Division of Emergency Medicine provides medical care to sick and injured children, under the leadership of Division Chief Dr. Keri Carstairs. The Division is comprised of the Sam S. and Rose Stein Emergency Care Center (ECC) at Rady Children s Hospital-San Diego (RCHSD), a pediatric track at Rancho Springs ED in Murrieta, along with four Urgent Care Centers (UCCs), which are managed under the leadership of Section Chief, Dr. Kathleen Konzen. FACULTY Our ECC is the only emergency care center in the San Diego region that is solely dedicated to the care of children. It is also the only Level 1 pediatric trauma center in San Diego County. Our emergency care center specializes in a host of services including evaluation and treatment of medical illnesses, treatment of minor injuries (including lacerations), acute orthopedic care, pediatric sedations, non-accidental injuries, stabilization and treatment of children with critical illnesses and trauma, poisonings, water submersion injuries, acute psychiatric illnesses, and the care of children with special needs, among others. Our UCCs provide after-hours pediatric care conveniently located at four different locations outside of our main campus. DIVISION FAST FACTS Keri Carstairs, MD Associate Professor of Clinical Pediatrics Chief and Medical Director Seema Shah, MD Associate Clinical Professor ; Clinical Director Joyce Arpilleda, MD Clinical Professor David Chao, MD Staff Physician Yu-Tsun Cheng, MD Staff Physician The only Level 1 Pediatric Trauma Center in San Diego County Over 86,000 patients entered Emergency Medicine's doors July 2014 thru June 2015 MAJOR PLANS AND GOALS Heather Conrad, MD Assistant Clinical Professor ; Medical Director, Rancho Springs Pediatric Track Joy Joelle Donofrio, DO Assistant Clinical Professor Arit Edwin-Enyenihi, MD Associate Clinical Professor Marc Etkin, MD Associate Clinical Professor ; Director of Informatics Clare Haas, MD Staff Physician Director of Simulation To improve clinical operations recently expanded to Riverside County, and to grow the Urgent Care team to a 5th site in San Diego County. To expand the fellowship program to include 3 pediatric emergency medicine fellows per year, and to start a new fellowship in pediatric point-of-care emergency ultrasound within 3 years. Jim Harley, MD, MPH Clinical Professor Cynthia Hoecker, MD Clinical Professor Paul Ishimini, MD Associate Clinical Professor of Emergency Medicine and Pediatrics; Pediatric Emergency Medicine John Kanegaye, MD Clinical Professor ; Research Director Simon Lucio, MD Clinical Professor To grow a new program dedicated to quality improvement, and pathway development to standardize the care provided. The development of an emergency medicine observation unit will help both the Division and hospital flow and capacity. To continue the expansion of a research program that will support fellows and faculty in their research endeavors. This will include the addition of an epidemiology team for research design and statistical support as well as the development of a research assistant program and emergency medicine faculty development program to provide needed mentorship. Mathew Murray, MD Assistant Clinical Professor of Pediatrics and Emergency Medicine; Co-Director, Pediatric Emergency Medicine Resident Education Margaret Nguyen, MD Assistant Clinical Professor ; Observation Medicine Director Kristy Putnam, MD, MPH Assistant Clinical Professor ; Associate Director of Quality Kristin Ratnayake, MD Assistant Clinical Professor Stacey Lynn Ulrich, MD Associate Clinical Professor 76 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 77

40 FACULTY FACULTY Urgent Care PEDIATRICIANS Atim Uya, MD Assistant Clinical Professor, Director of Ultrasound Shannon Wai, MD Assistant Clinical Professor,Co-Director of Pediatric Emergency Medicine Resident Education Amy Williams, MD Assistant Clinical Professor Elisa Zimmerman, MD Staff Physician Katherine Konzen, MD, MPH Clinical Professor, Medical Director Tom Bellomo, MD Staff Physician Shaun Berger, MD Staff Physician INTERMEDIATE CARE PEDIATRICIANS Trish Ghosh, MD Staff Physician Weena Joshi, MD Staff Physician Lauren Kearney, MD Staff Physician Gregory Langley, MD Associate Clinical Professor Wendy Hunter, MD Associate Clinical Professor, Lead Pediatrician Angelo del Re, MD Staff Physician Sarah Judd, MD Assistant Clinical Professor Naomi Lawrence-Reid, MD Staff Physician Seema Mishra, MD Assistant Clinical Professor Jennifer Tiller, MD Staff Physician Kamala Vaidya, MD Associate Physician Jamie Lien, MD Associate Clinical Professor Jane Lyons, MD Staff Physician Micheala Vigilante, MD Staff Physician Jennifer Weglowski, MD Associate Clinical Professor Winston Wu, MD Staff Physician Not Pictured: Hannah Awai, MD, Adam Braddock, MD, Jehrib Carbarlo, MD, Patricia Eck, MD, Elizabeth Filler, MD, Kara Hutton, MD, Jenny Ilfeld, Sarah Judd, MD, Kathy Smith, MD, Annemarie Selaya, MD and Joel Traut, MD, Kimberly Williard, MD, Corey Simpson, MD FELLOWS Sarah Combs, MD Margaret Huang, MD Michael Long, MD Naomi Abe, MD Karen Yaphockun, DO 78 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 79

41 CLINICAL CARE Our Emergency Care Center is the only center of its kind in the San Diego region, solely dedicated to the emergent care of children and is the only Level 1 pediatric trauma center in San Diego County. The Center specializes in the evaluation, diagnosis and treatment of a pediatric medical illnesses and traumatic injuries. Keri L. Carstairs, MD, FACEP began serving as chief and medical director of the Division of Emergency Medicine in July Dr. Seema Shah serves as Clinical Director; Dr. Heather Conrad serves as Medical Director for the pediatric track at Rancho Springs; Sue Cox, RN serves as interim Nursing Director. The ECC is the busiest pediatric emergency department on the West Coast. From July 2014 through June 2015, over 86,000 patients arrived in the ECC for treatment. This represents a greater than 15% increase in volume over the previous year. Despite this enormous increase in volume, our operational and patient satisfaction scores are at a record high. Our average Left Without Being Seen (LWBS) rate was less than 2% daily, and the average length of stay was 140 minutes. As we begin FY2016, our census continues to rise and we are estimated to see over 90,000 patients in our RCHSD ED, 9,000 in our Rancho Springs ED, and 60,000 in our urgent cares. Operations continue to improve, with a LWBS rate for FY2016 of 0.4% and length of stay of less than 130 minutes, both well below the industry benchmarks. Patient satisfaction scores also remain high. The ECC is the most common entrance for admitted patients at RCHSD. Ten percent of the patients that are seen in the ECC are admitted. This accounts for approximately 50% of the total admissions to RCHSD. ECC is the receiving unit for emergency transports brought in by paramedics via both ground and air transport. The Division provides continuous feedback and consultation regarding pediatric pre-hospital and disaster preparation and care in San Diego. The Division is also focusing on the care of pediatric mental health patients as the census of patients with mental health needs has tripled over the previous 2 years. This patient population presents a unique challenge to both the division and the entire hospital, as the patients require prolonged evaluation and observation, and often wait days to hours for inpatient beds. We have developed a working group to focus on improving care of these patients in the ED and to decrease boarding time. A mental health observation unit was opened in order to improve both capacity and the quality of care delivered. This resulted in 55% of mental health patients discharged home after observation, thereby avoiding unnecessary admissions. In 2015, the Department recruited Dr. Atim Uya, who has completed fellowship training in both pediatric emergency medicine and emergency ultrasound, who joined as Emergency Medicine Ultrasound Director. In this role, Dr. Uya has implemented a robust training program for all faculty and fellows to include formal and bedside training in pediatric point-of-care ultrasound. The use of ultrasound at the bedside in the ED is well known to improve quality of care and patient outcomes. To add to this initiative, the Department recently recruited a second attending physician with ultrasound training and will continue to build this valuable skillset for faculty and fellows. The Division's mission is focused on providing efficient, high quality care to every child who walks through our doors, while promoting excellence in pediatric education and research to improve the care of children in our community. The Division's vision is to increasingly become a national leader in high quality care, patient experience, clinical outcomes, research, and education with a team that is passionate and proud of what we do by providing the best outcomes for every patient every time. MEDICAL STAFF Provider staff is comprised of 28 board certified pediatric emergency medicine specialists, 10 board-certified pediatricians, and 2 nurse 80 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report CLINICAL ACTIVITIES practitioners. All pediatric emergency medicine specialists in the Division have completed residencies in Pediatrics or Emergency Medicine and 2 to 3 years of fellowship training in Pediatric Emergency Medicine. These pediatric emergency physicians work in all areas of our ED as well as at the satellite site in Murrieta. Pediatricians and nurse practitioners staff for less acutely ill and injured guests in the Intermediate Care and fast-track areas of our emergency center. QI INITIATIVES Beginning in October 2014, the Division began a quality improvement initiative (QI) to further the mission of improving care for our patients. The process began with the appointment of a Clinical Director, Dr. Seema Shah, to specifically oversee this initiative. In addition, the Emergency Department Quality Assessment and Performance Improvement (ED QAPI) committee with the oversight from the Dr. Glenn Billman, Chief Safety Officer at RCHSD were created. The committee consists of a multidisciplinary team consisting of physicians, fellows, registered nurses, respiratory therapists and informaticists; additionally, >75% of our faculty and fellows on projects, guidelines and pathways, with over 25 active quality improvement projects. Faculty members in the division are required to be involved in at least one project each year. Projects include: Bronchiolitis: In conjunction with the hospital-based multidisciplinary pathway group, the pathway was reorganized to be consistent with the 2014 American Academy bronchiolitis guidelines. After implementation of the new pathway and order set, this markedly decreased the unnecessary use of beta agonist therapy. Handoff: The field of Emergency Medicine is particularly susceptible to serious errors due to frequent interruptions, rapid turnover of patients, and a high stress environment. The Division has created a standardized handoff tool to be use by all emergency providers. This provides the ability to track usage of the tool, in addition to monitor the number of handoffs are occurring. Appendicitis: as a part of the Gastroenterology service line, a new pathway was developed with pediatric surgeons and radiologists to institute the use of ultrasound for appendicitis. This pathway also includes the utilization of an order set and attempts to streamline management of patients in the units. Asthma: The Division developed a new asthma pathway after review of best practice guidelines and discussions with pediatric emergency care providers in the US. This new algorithm involved the creation of an EMR-based order set. To further facilitate flow of care, the Division instituted widespread education of nurses, respiratory therapists and emergency physicians. As a result, the time to first dose of steroids and beta agonist therapy decreased, while pathway utilization increased in the ED. Concussion: The increase in public and pediatric specific awareness regarding concussions led to the development of a streamlined approach to management of patients with concussions in conjunction with rehabilitation specialists. DISASTER PREPAREDNESS The Department has recently recruited Dr. Joelle Donofrio as EMS director, who has specialized training in both disaster medicine and emergency medical services. She is currently in the process of improving both Division's and the hospital s approach to disaster preparedness in order to help make us ready to be the first linereceiving unit for pediatric disaster victims. EMERGENCY MEDICAL SERVICES The Division provides advice and direction to the County and City of San Diego in pre-hospital care. We strive to ensure that paramedics are properly supplied with the necessary equipment, education, and protocols to assess and stabilize sick and injured children before they are brought to the hospital. RESIDENTS AND MEDICAL STUDENTS Education is a vital mission of the Division which currently educates over 200 residents from residency programs in Pediatrics, Emergency Medicine, and Family Medicine located in San Diego. Residents are trained to recognize and stabilize sick and injured children and performed emergency procedures on pediatric patients. Drs. Matthew Murray and Shannon Wai currently serve as Directors of resident education. UCSD medical students rotate with the Division. Dr. Michele McDaniel directs our medical student education and has expanded this program substantially over the past year to include medical students in their 3rd year as well as those rotating at UCSD Hillcrest. The fourth-year UCSD medical student rotation is one of the most popular selections among students interested in pediatrics or emergency medicine. FELLOWSHIP The Division of Emergency Medicine runs an ACGMEaccredited two- to three-year fellowship program in pediatric emergency medicine. Currently, there are six fellows-intraining; Dr. Paul Ishimine is the Fellowship Director. Training future pediatric emergency medicine physicians is a key priority of the Division to help meet this need. We currently match 3 fellows per academic year; upon completion CURRENT RESEARCH Dr. John Kanegaye continues to champion the Division's research efforts as Research Director. Division-wide, there are 18 active studies, with over 30 proposals in various stages. Division members presented their work as one abstract at the American College of Emergency Physicians Scientific Assembly, October 2015, and with 9 abstracts at the Quigley Symposium in November 2015, which included winner and runner-up for Best Abstract award. An additional seven abstracts await decisions from military, national, and international meetings. Since July 2015, Division authors have published or had accepted six original research articles, of which four have Division members as first or senior authors. Two resulted from PEM fellowship projects, one from the Pediatrics Residency Program, and four resulted from KD research. Five manuscripts are under review at high impact journals including the NEJM, Lancet, BMC Pediatrics, PLOS ONE, and Pediatrics. Supporting their efforts, 2 Division investigators have secured extramural funding. A CHANGE IN THE RESEARCH ENVIRONMENT Although the ECC is a rich source of material for clinical research, in the past, clinical obligations have taken priority over research. Historically, the academic output by the Division has depended upon the sporadic unfunded efforts of full-time clinicians. Despite creative efforts to increase research activity (for, example, most of the DEM s KD publications or submissions used subjects recruited by the Pediatric Emergency Medicine Kawasaki Disease Research Group), potential subjects were more often lost than recruited. In comparison, truly successful academic PEM programs use statistical support and research assistant (RA) coverage. However, the Division is in the process of changing TEACHING ACTIVITIES of fellowship, fellows have obtained positions in academic institutions nationwide, including UCSD. SIMULATION A pediatric emergency medicine simulation director was recently appointed. This is an emerging area of increasing educational importance that helps future clinicians learn to care for children as well as maintains the skills of our faculty. Fellows, residents and students are educated monthly via this robust simulation program, which is an area of continued growth for the Division's academic mission. EDUCATION AND OUTREACH Drs. Ishimine and Shah have hosted eight Pediatric Emergency Medicine Regional conferences, occuring biannually, which have drawn audiences from around the county. The target audience is emergency medicine trainees and faculty, with a goal of improved pediatric care at emergency departments throughout the county. Division faculty members continue to provide lectures both within and outside the confines of the university at regional and national meetings. Several members have also published articles in public news magazines directed at educating the public. RESEARCH ACTIVITIES its research environment. With generous support from the Rady Children s Hospital Academic Enrichment Fund Award, the Division's research infrastructure is expanding. Kathryn Hollenbach, PhD, MPH and Karen Ferran, PhD, MSPH, professional epidemiologists and biostatisticians were recently hired to provide research support via monthly research methodology lectures, biostatistical support, and scientific writing expertise. Additionally, Dr. Hollenbach is in the process of obtaining training to become an EPIC analyst to help with extraction of data from EPIC, RCHSD's electronic medical record system, in order to support the Division's research efforts. In addition, Drs. Hollenbach and Ferran are spearheading the development of a new research assistant (RA) program: On-site RAs will enhance clinical research endeavors by extracting data for retrospective clinical and quality assurance studies and providing real time data collection for our prospective clinical studies. As of January, 12 RAs have been identified and are currently undergoing the on-boarding procedure, and an additional 15 applications have been received and are currently under review. All of these efforts will result in improved support for the faculty to increase academic output. HUMAN SUBJECT STUDIES Yung Y, Nguyen M, Chun J. CSF Lysophospholipid biomarker in hydrocephalus. IRB Approved October Carstairs S, Carstairs K, Yaphockun K, Hollenbach K, Ferran K. A retrospective review of antipsychotic medication administration for agitated psychiatric patients in a tertiary care pediatric hospital emergency department. IRB approved. Carstairs S, Carstairs K, Yaphockun K, Ferran K, Hollenbach K. A retrospective review of administration of physostigmine at a tertiary Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 81

42 care pediatric hospital in patients with suspected antimuscarinic poisoning. IRB approved. Williams A, Bonsu B, Johnson AL, Pommert KBJ, Hollenbach KA, Kanegaye JT. Tablet computer as a distraction tool during facial laceration repair: A randomized trial. Data analysis and manuscript in progress. Auten J, Pennock A, Naheedy J, Hurst N, Kanegaye JT. Ultrasoundand Fluoroscopy-Guided Reduction Of Pediatric Forearm Fractures: A Prospective Observational Study. Data analysis in progress. Ishimine P, RCHSD site investigator for the AAP Pediatric Emergency Medicine Collaborative Research Committee. Herpes simplex virus infection in infants. Manuscript and substudy in progress. Ishimine P, RCHSD site investigator for Pediatric Research in Inpatient Settings Network. Pediatric Intravenous Versus Oral antibiotic Therapy (PIVVOT) study. Manuscript for substudy on perforated appendicitis in progress. Huang M, Magana J, Malicki D, Schroter S, Clark R, Kanegaye JT. Child protection and toxicologic outcomes of young children with positive urine drug screens in a pediatric emergency department. IRB Research Plan approved 11/3/15. Data collection in progress. Combs S, Shah S, Kanegaye JT. Clinical characteristics identifying low-risk young infants presenting to the ED. Requirement for IRB approval and consent waived (6/12/15). Huang M, Wai S, Fairbanks T. Retrospective study of diagnostic utility of D-dimer in minor head trauma. Long M, Nguyen M, Del Re A, Wu W, Kanegaye JT. Positional differences in lumbar spaces among infants in lateral flexed versus seated flexed position. Patient enrollment in progress. Nguyen M, Lizardo E, Bickler S, DiMaio A. Urine biomarkers in the diagnosis of acute appendicitis. IRB approved, study collection to be started. PEM fellows, Carstairs K, Fairbanks T, Magit A. Prospective study of telemedicine in the diagnosis of acute appendicitis. Elkhunovich M, Liu D, Arpilleda J, Clingenpeel J, Mansour K, Reich T, Yen K, Wang V. The incidence of UTIs in febrile infants 2-12 months of age with bronchiolitis. Patient enrollment completed in fall Abstract submitted. Putnam K, Carstairs K, Bonsu B, Kanegaye JT. Urine cytometric urinalysis as a predictor of UTI and bacteremia in young febrile infants. Data collection in progress. Kanegaye JT, Tremoulet AH, Burns JC, Ling BX. Biomarker and diagnostic algorithm to differentiate Kawasaki disease from other febrile illnesses. Patient enrollment in progress. Magana J, Kanegaye JT, in collaboration with emergency and child abuse investigators at Lurie Children s Hospital, Chicago IL and Cincinnati Children s Hospital Medical Center, Cincinnati OH, and Kosair Children s Hospital, Louisville KY. Clinical decision rules to discriminate bruising caused by physical child abuse from bruising caused by accidental trauma. Data analysis in progress. Shah S, Hollenbach K. Utilization of the asthma pathway to improve asthma management in a pediatric emergency department. Requirement for IRB approval and consent waived (date). Tamas V, Madati J, Ishimine P. D- and L-lactate levels as biomarkers for intussusception. Manuscript under revision for resubmission. Carstairs K, Carstairs S, Hollenbach K, Ferran K. A retrospective review of home use of mood stabilizing medications prior to presentation for psychiatric illnesses to a tertiary care pediatric hospital emergency department. IRB Research Plan under review. Donofrio J, Wu W, Saenz N, Hollenbach K, Carstairs K. Retrospective evaluation of a lateral cervical radiograph and cervical collar for midline cervical tenderness in low risk pediatric trauma patients. IRB submission in progress. Nguyen, M, Hollenbach K, Ferran K, Castillo E. Understanding return visits to the pediatric emergency department: A patientcentered outcomes pilot study. IRB submission in progress. Davenport K, Bickler S, Nguyen M. Spatial analysis and Pediatric Appendicitis study. IRB approved. Modification of IRB Research Plan in progress. Guyon P, Nguyen M, Ferran K, Hollenbach K, O Toole P. Trends in injuries related to cellphone use in children and teens. Awaiting IRB classification as exempt from review. Nguyen M, Murray M, RCHSD site investigators for NEAR 4 KIDS. Survey of Emergency Airway Procedures in Pediatric Emergency Department: National Emergency Airway Registry. DUA executed. Revised IRB research plan under review. Yaphockun K, Kaufhold M, Dwek J, Kanegaye JT. The additional yield of lateral radiographs centered on lower extremity joints in identifying fractures on skeletal surveys. Research plan in progress. McDaniel M, Arpilleda J. Pediatric emergency provider use of medications for analgesia, sedation, and anxiolysis during reduction of anterior shoulder dislocations. IRB approved, RTA letter received. Carstairs K, Fero K, Hollenbach KA. Retrospective assessment of a validated Pediatric Early Warning Score (PEWS) in a pediatric emergency department. Awaiting IRB Submission. Carstairs K. A Retrospective review of naloxone use in a tertiarycare pediatric hospital. IRB research plan submitted (1/13/16). Carstairs K, Hollenbach K, Shah S, Putnam K, Black I, Weber R. Utilization of Seasonal Demand Capacity Analysis to Improved Pediatric Emergency Department Metrics and Patient Satisfaction Scores in a Pediatric Emergency Department. In planning phase. Carstairs K, Abe E, Uya A, Ratnayake K, Williams A, Hollenbach K. Comparison of Point of Care Ultrasound to MRI for the Evaluation of Appendicitis in a Pediatric ED. In planning phase. Carstairs K, Chan T. Pediatric Emergency Department Staffing: Comparison of mid-level providers, emergency physicians, and pediatricians. In planning phase. Conrad H, Carstairs K, Lucio S, Ratnayake K. Reduction in the length of stay for pediatric patients in a community ED after the implantation of a pediatric track staffed by pediatric emergency physicians. Same as #6-QI project with a plan for retrospective review. Dunford J, Kahn C, Donofrio J, Groebel M, Pierce J. A retrospective analysis of prehospital treatment of LVAD patients in San Diego. Collaboration with UCSD, San Diego City Fire. IRB proposal in progress. Donofrio J, Kahn C. Use of a field hospital in a multi-agency multicasualty incident drill. IRB proposal submitted. Donofrio J, Kahn C. Criteria Outcomes Tool Validation of Mass Casualty Algorithms in Pediatric population. IRB proposal submitted. Donofrio J, Zimmerman E. Adding RCHSD to the Accuvein RCT Carstairs K, Donofrio J, Chao D. PsySTART pediatric singleton trauma PTSD prediction study. Prospective multicenter collaborative study with UCI and Harbor UCLA. IRB proposal submitted. PUBLICATIONS Ling XB, Kanegaye JT, Ji J, Peng S, Sato Y, Tremoulet AH, Burns JC, Cohen HJ. Point-of-care differentiation of Kawasaki disease from other febrile illnesses. J Pediatr. 2013;162(1): PMID: Kanegaye JT, Van Cott E, Tremoulet A, Salgado A, Shimizu C, Kruk P, Hauschildt J, Jain S, Sun X, Burns JC. Lymph-node-first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr. 2013;162(6): PMID: PMCID: PMC Shimizu C, Kim J, Stepanowsky P, Trinh C, Lau HD, Akers JC, Chen C, Kanegaye JT, Tremoulet A, Ohno-Machado L, Burns JC.. Differential expression of mir-145 in children with Kawasaki disease. PLoS One. 2013;8(3):e PMID: ; PMCID: PMC Burns JC, Song Y, Bujold M, Shimizu C, Kanegaye JT, Tremoulet AH, Franco A. Immune-monitoring in Kawasaki disease patients treated with infliximab and intravenous immunoglobulin. Clin Exp Immunol. 2013;174(3): PubMed PMID: ; PMCID: PMC Ishimine P, Kanegaye J, indexed working group authors in: Dalziel SR, Thompson JM, Macias CG, Fernandes RM, Johnson DW, Waisman Y, Cheng N, Acworth J, Chamberlain JM, Osmond MH, Plint A, Valerio P, Black KJ, Fitzpatrick E, Newton AS, Kuppermann N, Klassen TP; Pediatric Emergency Research Networks H1N1 Working Group. Predictors of severe H1N1 infection in children presenting within Pediatric Emergency Research Networks (PERN): retrospective case-control study. BMJ Aug;347:f4836. PMID: ; PMCID: PMC Ogata S, Shimizu C, Franco A, Touma R, Kanegaye JT, Choudhury BP, Naidu NN, Kanda Y, Hoang LT, Hibberd ML, Tremoulet AH, Varki A, Burns JC. Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G. PLoS One Dec;8(12):e PMID: ; PMCID: PMC Ishimine P, Kanegaye J, indexed authors in: Schnadower D, Kuppermann N, Macias CG, Freedman SB, Agrawal D, Mao J, Dayan PS; American Academy Pediatric Emergency Medicine Collaborative Research Committee UTI Study Group. Outpatient management of young febrile infants with urinary tract infections. Pediatr Emerg Care Sep;30(9): PMID: Kanegaye JT, Jacob JM, Malicki D. Automated urinalysis and urine dipstick in the emergency evaluation of young febrile children. Pediatrics Sep;134(3): PMID: Tremoulet AH, Jain S, Jaggi P, Jimenez-Fernandez S, Pancheri JM, Sun X, Kanegaye JT, Kovalchin J, Printz BF, Ramilo O, Burns JC. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet May;383(9930): PMID: Franco A, Touma R, Song Y, Shimizu C, Tremoulet AH, Kanegaye JT, Burns JC. Specificity of regulatory T cells that modulate vascular inflammation. Autoimmunity Mar;47(2): PMID: Lumba-Brown A, Harley J, Lucio S, Vaida F, Hilfiker M. Hypertonic saline as a therapy for pediatric concussive pain: a randomized controlled trial of symptom treatment in the emergency department. Pediatr Emerg Care Mar;30(3): Wardi G, Ishimine P, Lasoff D, Yuan C, Campbell C. An unusual case of an icteric infant with abdominal distention. J Emerg Med Jul;47(1): Epub 2014 Mar 20. PubMed PMID: Ishimine P, indexed author in: Keren R, Shah SS, Srivastava R, Rangel S, Bendel-Stenzel M, Harik N, Hartley J, Lopez M, Seguias L, Tieder J, Bryan M, Gong W, Hall M, Localio R, Luan X, deberardinis R, Parker A. Pediatric Research in Inpatient Settings Network. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr Feb;169(2): PMID: Work conducted outside of UCSD/RCHSD: Thota D, Zanoni S, Mells C, Auten JD. Acute, proximal aortic dissection with negative d-dimer assay and normal portable chest radiograph: a case report. Mil Med Jan;180(1):e doi: /MILMED-D PubMed PMID: Auten JD, Ross EM, French MA, Li IZ, Robinson L, Brown N, King KJ, Tanen DA. Low-Fidelity Hybrid Sexual Assault Simulation Training's Effect on the Comfort and Competency of Resident Physicians. J Emerg Med Nov 27. pii:s (14) doi: /j.jemermed [Epub ahead of print]pubmed PMID: SCIENTIFIC PRESENTATIONS Ogata S, Shimizu C, Kanegaye J, Choudhury B, Varki A, Burns JC, Tremoulet AH. Sialic acid modification of IgG in patients with Kawasaki disease. Poster presentation, Building Bridges for Child Health: Pediatric Translational Research Symposium (UCSD Department and Rady Children s Hospital San Diego), February 1, 2013, La Jolla, California. Rudinsky S, Sharieff GQ, Law W, Kanegaye JT. Adverse clinical events among pediatric emergency department patients hospitalized after multiple dose administration of racemic epinephrine for croup. Poster presentation, 28th Annual Academic Research Competition, Naval Medical Center San Diego, April 12, Magana JN, Kanegaye JT, Kaczor K, Lorenz DJ, Bennett BL, MD, Meyers G, Hickey S, Pierce MC. The low prevalence of bruising in the first year of life among infants presenting to pediatric emergency departments. Poster presentation, 2013 Ray E. Helfer Society Annual Meeting, April 14-17, 2013, Sonoma, CA. Trinh C, Shimizu C, Kim J, Kanegaye JT, Tremoulet A, Burns JC..Whole blood microrna profiles in adenovirus-infected children. Poster presentation at the 2013 Pediatric Academic Societies' Annual Meeting, Washington, DC, May 4, Shimizu C, Kim J, Stepanowsky P, Trinh C, Lau HD, Akers J, Chen C, Kanegaye JT, Tremoulet A, Ohno-Machado L, Burns JC.. Differential expression of mir-145 in children with Kawasaki disease. Poster presentation at the 2013 Pediatric Academic Societies' Annual Meeting, Washington, DC, May 4, Ogata S, Shimizu C, Kanegaye J, Choudhury B, Varki A, Burns JC, Tremoulet AH. Treatment response and monosaccharide modification of IgG in patients with Kawasaki disease. Platform presentation at the 2013 Pediatric Academic Societies' Annual Meeting in Washington, DC, May 4, UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 83

43 Shimizu C, Huang CYJ, Phan-Huy A, Salgado AP, Antonio L, Kanegaye JT, Tremoulet AH, Franco A, Burns JC. Lysyl oxidase expression in the patients with Kawasaki disease. Platform presentation, 2015 International Kawasaki Disease Symposium, Honolulu, HI, February 3, Hao S, Jin B, Tan Z, Li Z, Ji J, Kanegaye JT, Tremoulet AH, Burns JC, Cohen HJ, Ling XB. An Improved Point-of-Care Differentiation of Kawasaki Disease from Other Febrile Illnesses. Platform presentation, 2015 International Kawasaki Disease Symposium, Honolulu, HI, February 4, Li Z, Tan Z, Hao S, Jin B, Liu X, Zhang J, Jin H, He Z, Wang H, Kanegaye JT, Tremoulet AH, Burns JC, Wu J, Cohen HJ, Ling XB. Discrimination of Kawasaki Disease from Other Febrile Illnesses with a Urinary Colorimetric Sensor Array. Poster presentation, 2015 Pediatric Academic Societies' Annual Meeting, San Diego, CA, April 26, Castillo E, Chan T, Vilke G, Hsia R, Ishimine P, Shah S, Kapoor K, Brennan J. A description of pediatric frequent users of Emergency Department resources. American College of Emergency Physicians Scientific Assembly. Boston, MA; October Carstairs K; Hollenbach K; Shah S; Weber R; Black I; McDonough L; Lopez B; Kaufma, I; Davis C. Improved Emergency Department Quality Metrics and Patient Satisfaction Scores Following Implementation of Lean Flow Principles and Queuing Theory-Based Operational Changes. Poster presentation, 2015 Ed Quigley Clinical Research Symposium, Rady Children's Hospital San Diego, November 5, Castillo E, Chan T, Vilke G, Hsia R, Ishimine P, Shah S, Kapoor K, Brennan J. A description of pediatric frequent users of Emergency Department resources Ed Quigley Clinical Research Symposium. Rady Children s Hospital, San Diego. San Diego, CA; November Kanegaye JT, Jones JM, Burns JC, Jain S, Sun X, Jimenez- Fernandez S, Berry E, Pancheri JM, Jaggi P, Ramilo O, Tremoulet AH. Axillary, oral, and rectal routes of temperature measurement during treatment of acute Kawasaki disease. Poster presentation, 2015 Ed Quigley Clinical Research Symposium, Rady Children's Hospital San Diego, Nov. 5, Williams A, Bonsu B, Johnson A, Pommert K, Hollenbach K, Kanegaye J. Tablet computer as a distraction tool during facial laceration repair. Poster presentation, 2015 Ed Quigley Clinical Research Symposium, Rady Children's Hospital San Diego, November 5, Rudinsky S, Sharieff G, Law W, Kanegaye J. Inpatient treatment after multi-dose racemic epinephrine for croup in the Emergency Department. Poster presentation, 2015 Ed Quigley Clinical Research Symposium, Rady Children's Hospital San Diego, November 5, Guyon P, Nguyen M, Ferran K, Hollenbach K, O Toole P. Trends in Injuries Related to Cellphone Use in Children and Teens. Poster presentation, 2015 Ed Quigley Clinical Research Symposium, Rady Children's Hospital San Diego, November 5, Nguyen M, Castillo E. Spatial Analysis of Asthma Emergency Department Visits in California. Poster presentation (Runner up for Outstanding Abstract Award winner), 2015 Ed Quigley Clinical Research Symposium, Rady Children's Hospital San Diego, November 5, Tamas V, Madati J, Ishimine P. Utility of Lactic Acid Levels in Children with Suspected Intussusception. Poster presentation, 2015 Ed Quigley Clinical Research Symposium, Rady Children's Hospital San Diego, November 5, Chaparro JD, Doan S, Maehara CK, Hsu CN, Kanegaye JT, Lloyd DD, Burns JC, MD, Tremoulet AH, Pediatric Emergency Medicine Kawasaki Disease Research Group. Building a Natural Language Processing Tool to Identify Patients with High Clinical Suspicion for Kawasaki Disease from Emergency Department Notes. Oral presentation (Outstanding Abstract Award winner), 2015 Ed Quigley Clinical Research Symposium, Rady Children's Hospital San Diego, November 5, AWARDS Keri Carstairs, MD Rady Children s Hospital Physician of Excellence Award 2014 Jonathan Auten, DO New Speakers Forum, ACEP 2014 Matthew Murray, MD 2nd Place-Western Society for Academic Emergency Medicine New Speaker Forum University of California San Diego Emergency Medicine faculty Teacher of the Year award 2015 Cindy Hoecker, MD AAP Pediatric Emergency Medicine PEM Pix Competition Winner 2015 John Kanegaye, MD Top Doctor, San Diego County Medical Society 2014 Excellence in Teaching Award, Rady Children s Hospital 2014 Paul Ishimine, MD Top Doctor, San Diego County Medical Society 2014 Top Doctor, San Diego County Medical Society 2015 Seema Shah, MD Top Doctor, San Diego County Medical Society 2015 Under the leadership of Dr. Katherine Konzen, Urgent Care Medical Director, the Urgent Care Centers (UCC) saw over 50,000 patients at four off-site urgent care facilities last year, a 15% increase from the previous year. UCC provide nearby access to local communities so that parents and patients do not need to travel to the RCHSD Emergency Department and provide quick access to board-certified pediatricians and pediatric-trained nurses when the family s doctor or pediatrician s office is closed evenings and weekends. Our clinics provide afterhours care 365 days a year. The sites are open 4pm-10pm weekdays and holidays, and 1pm-10pm on weekends. The Urgent Care Center Teams of Physicians, Nurses and Patient Access Reps have held an annual retreat over the past 5 years to conduct team building and to collectively solve challenging issues. The section meets monthly as a team to discuss efficiency and patient satisfaction, with the focus on systems issues to improve care. The high commitment to efficiency and quality, by the team accounts for the large number of patients that UCC is able to see and treat. UCCs transfer 2-4 % of patients to the Emergency Department/or Inpatient Unit. Overall, UCC is able to care for 96% of requesting patients and families. SECTION OF URGENT CARE u CLINICAL CARE OFF-CAMPUS SITES The North County Urgent Care is located at 625 W. Citracado Parkway, Suite 100, in the North County Medical Office Building. RCHSD leases space to run CCS specialty clinics during the day and the Urgent Care Center in the evenings and weekends. This site is located off Interstate 15 on the corner of Felicita and Citracado Parkway. Our team of providers treat over 13,000 patients per year at North County. The East County Urgent Care facility was re-opened in March 2008 on the Grossmont Medical Center Campus. This Urgent Care facility is conveniently located for people who live in East County communities such as La Mesa or El Cajon. This site has grown significantly since its re-opening, and we treat over 12,000 patients per year at East County. The Mid-City Clinic was designed to provide comprehensive services for a largely underserved population in City Heights based on a creative model. The Mid-City Clinic sees primary care patients at the site during the day. The Urgent Care team sees patients in the evening, and provides service that is unparalleled in quality and efficiency to an area where most patients must use public transportation to travel beyond their neighborhoods. This site provides services seven days a week and is open until 10pm. We treat 18,000 per year at Mid-City. The North Coastal Clinic is located in Oceanside and is a collaborative effort between Sanford clinics, CPCMG, CSSD Specialty Clinics and RCHSD. The Urgent Care shares space with the Specialty clinics. This site opened in April of 2010, with over 12,000 patients treated per year. 11,269 seen patients through the end of the fiscal year. This site continue to grow at this site with a 40% increase in census the past year. TEACHING ACTIVITIES There are 2-week long elective rotations for UCSD Pediatric Residents and Family Medicine Residents at the UCCs. Family practice residents from Scripps also do a 2-week rotation with us. Education is a commitment in our program. Drs. Trish Ghosh and Jennifer Tiller have taken the lead as the coordinators of our educational program. In addition, there is a mandatory 2-week rotation for all UCSD Pediatric residents in the Intermediate Care of the Emergency Department or in the UCCs. Physicians participate in the education of residents, medical students and nurse practitioner students. 84 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 85

44 Endocrinology 86 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 87

45 INTRODUCTION FACULTY The Division of Endocrinology is actively engaged in clinical care, research, teaching and community service in the areas of endocrinology, diabetes, lipid disorders and obesity. The Division has continued to expand its clinical and research activities to meet the ongoing health needs of the San Diego pediatric community. DIVISION FAST FACTS $7.4 million in research grants over 1,400 children with type 1 or type 2 diabetes seen routinely in the clinic Michael Gottschalk, MD, PhD Clinical Professor of Pediatrics, Division Chief Carla Demeterco, MD, PhD Assistant Clinical Professor Wexnian Fu, PhD Assistant Professor Ergeng Hao, MD Associate Project Scientist Ulupi Jhala, PhD Associate Adjunct Professor MAJOR PLANS AND GOALS Kenneth Lee Jones, MD Professor Emeritus Thomas Kelly, MD Assistant Clinical Professor Jane Kim, MD Staff Physician Charles King, PhD Associate Research Scientist Karen Klein, MD Staff Physician To build a pediatric diabetes center in San Diego! To merging independent programs into a single center Janel Kopp, PhD Associate Research Scientist Maja Marinkovic, MD Staff Physician Ron Newfield, MD Clinical Professor Susan Phillips, MD Staff Physician Liping Qiao, PhD Associate Project Scientist To focus research on islet cell regeneration, including stem cell initiatives, immune-based interventions in recent onset of type 1 diabetes mellitus, and crucial collaborations that interlace biological approaches to devise new avenues to treat and prevent type 1 diabetes mellitus To create a clinical research program for obesity and related consequences, directed toward prevention and treatment of obesity, insulin resistance, fatty liver disease, metabolic syndrome and dyslipidemia Jianhua Shao, MD, Phd Associate Professor Maike Sander, MD Professor Director, Pediatric Diabetes Research Center Hiba Al-Zubedi, MD Jennifer Concepcion, MD Bjoern Gaertner, Ph.D. Sajal Kadakia, MD Wen Jin, Ph.D. Zoya Kai, PhD Francesca Mulas, Ph.D. FELLOWS Kim-Vy Nguyen-Ngoc, PhD Maria Eleni Nikita, MD Ben Shih, Ph.D Allen Wang, PhD Matthew Wortham, PhD Ruiyu Xie, PhD Chun Zeng, Ph.D 88 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 89

46 The Division of Pediatric Endocrinology cares for children with endocrine disorders, lipid disorders and diabetes mellitus. The division is a participant in the multidisciplinary Prader-Willi clinic and Neuro-Oncology Clinic. Recently the division established the Gender Management Clinic to provide care for transgender Children s and adolescents. Outpatient endocrinology clinics are located at Rady Children s Hospital San Diego (RCHSD) and in satellite offices in San Diego, Imperial and Riverside Counties. Over the past year, there The Division s accredited three-year fellowship program trains up to three fellows in clinical and basic science research. The program combines clinical and research training throughout the program, with the first year focused on an in-depth clinical experience. The second and third years provide time for focused development of research interests. Carla Demeterco, MD, PhD Dr. Demeterco supervises medical students, residents and fellows in the endocrine/diabetes clinic and lectures at resident and fellow conferences. She is a preceptor at the Fellows Endocrine Clinic. She serves as a clinical mentor to pediatric residents and is currently a research mentor to a UCSD Pediatric Pulmonology Fellow, on a project studying the use of continuous glucose monitoring to predict pulmonary exacerbation in cystic fibrosis. Wenxian Fu, PhD Dr. Fu teaches a core class (biom201) for first year graduate students in the Biomedical Sciences Graduate Program. Dr. Fu supervises postdoctoral fellows, graduate students, and undergraduate researchers in her laboratory. Michael Gottschalk, MD, PhD Dr. Gottschalk is the Pediatric Endocrinology Fellowship Program Director and Vice-Chair for Education in the Department. As such, he is very involved in resident and fellow education. He teaches in the first-year medical student Endocrinology Reproductive Medicine and Metabolism course, precepts medical students in the endocrine/diabetes clinic and is chair for a medical student independent study project. In addition, he was invited to speak at meetings of the Endocrine Society and has been interviewed on local television. Andrew Hinton, PhD Dr. Hinton teaches an online course in Stem Cell Biology at UCSD extension, and he mentors undergraduate researchers in his laboratory. Kenneth Lee Jones, MD Dr. Jones continues to work with students, rotating residents and pediatric endocrinology fellows in the pediatric diabetes and endocrinology clinics. He also spends one week each month as the inpatient-attending physician on the pediatric endocrine/diabetes service. In this capacity, he rounds with the resident/student team for an hour each morning. 90 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report CLINICAL ACTIVITIES were more than 16,000 endocrine/diabetes outpatient visits, and over 1,400 children with either type 1 or type 2 diabetes mellitus were routinely seen by the diabetes service. The Diabetes Center at RCHSD received the American Diabetes Association Recognition Award for meeting the standards of education in diabetes self-management. TEACHING ACTIVITIES Jane Kim, MD Dr. Kim provides lectures to residents and fellows, and teaches in the endocrine/diabetes clinic. She also serves on a fellowship scholarship oversight committee and is an instructor and mentor for undergraduate, graduate and medical students. Charles King, PhD Dr. King lectures to graduate studies on insulin signal transduction and on sirna/mirna. Additionally, Dr. King mentors two Masters students and three undergraduate students. He serves on the Review and Appraisals Committee. Karen Klein, MD Dr. Klein teaches medical students, residents and fellows in the endocrinology clinic. She has served as a mentor for endocrine fellows and served on 2 fellowship scholarship oversight committees. Maja Marinkovic, MD Dr. Marinkovic teaches endocrine fellows, pediatric residents and medical students in inpatient and outpatient settings. She gives lectures for pediatricians, students and residents at pediatric grand rounds at Mercy Hospital. She has given lectures in the first-year medical student Endocrinology and Metabolism course. She served on the ISP committee. Ron Newfield, MD Dr. Newfield is responsible for organizing the three-year endocrinology-diabetes fellowship lecture series. He is also in charge of Journal Club. He is involved in medical student, resident and fellowship education. He was the mentor for one of the Endocrine fellows for her main project, which just got published. He also worked with another endocrine fellow and a UCSD student on a clinical research project about vitamin D in new onset diabetes, that was published. He serves on a fellowship scholarship oversight committee. Susan Phillips, MD Dr. Phillips teaches medical students, interns, residents and fellows in the outpatient pediatric diabetes and endocrinology clinics as well as in the UCSD/VA diabetes outpatient clinic. She serves as an instructor in the Endocrinology and Metabolism course for first and second year medical students. She provides didatic lectures on a variety of topics in diabetes and endocrinology to rotating medical students, housestaff and fellows at Rady s and the VA Medical. She continues serve as an ISP to one student yearly and to mentor rotating undergraduates and medical students in the laboratory. Dr. Phillips also serves as a member of the core curriculum committee involved in the policy and administration of medical student education. Carla Demeterco Berggren MD PhD research interests are in developmental therapeutics for diabetes mellitus. She has worked extensively in the area of pancreatic beta cell biology with emphasis on inducing beta cell regeneration in the adult human pancreas. She is the principal investigator on the study of the effects of the bile acid sequestrant, Colesevelam in children with type 2 diabetes mellitus. She is also the principal investigator on a study evaluating the role of continuous glucose monitoring in predicting pulmonary exacerbation in children with cystic fibrosis. She is involved as a sub investigator in numerous clinical trials related to both type 1 and type 2 diabetes mellitus. Ron Newfield, MD has developed and is maintaining a comprehensive database of endocrinology and diabetes patients seen at Rady Children s Hospital-San Diego. He also has a type 1 diabetes-specific retrospective study to assess weight gain and glycemic response to insulin as well as evaluating other conditions at presentation. The database and diabetes-specific protocols have already enabled publication of manuscripts and abstracts, and will remain a valuable source for future research in pediatric diabetes and endocrinology. Dr. Newfield has involved in clinical trials of growth hormone treatment in children with idiopathic short stature, a study to assess QOL in children with short stature, which resulted in publications on which he is a co-author. HE was also involved in a clinical trial to assess the pharmokinetics and efficacy in children of a lipid-lowering medication. Dr. Newfield is the PI of a TrialNet affiliate site at Rady Children s Hospital that has tested 800 subjects that are relatives of patients with type 1 diabetes for their risk of developing the disease as well, which is part of a multicenter network in the US and abroad. As part of TrialNet he is also running two intervention/prevention trials for those relatives who test positive for type 1 diabetes antibodies. Dr Newfield has 2 industry-based studies with subjects already enrolled, and 1 more ready to recruit.he also initiated a study in collaboration with Quest Diagnostics, to retrospectively evaluate thyroid tissue from pediatric thyroid cancer surgical specimens, and assess the frequency of different mutation classes, and genotype vs. phenotype correlations. Dr Newfield has submitted a provisional patent and had a publication about a new formulation of a known diabetic medication, to try and treat excessive hair, and is planning to start a pilot (proof of concept) trial. Susan Phillips, MD translational research is focused on improving our understanding of the development of metabolic diseases such as diabetes and fatty liver disease in human obesity. Obesity is recognized to increase the risk of developing type 2 diabetes, yet only about 20% of obese Maike Sander, MD Dr. Sander is co-lecturer of the Stem Cell Biology Course that is mandatory for graduate students, postgraduate researchers, and clinical fellows who receive support by the California Institute of Regenerative Medicine (CIRM). She also coteaches a core class for first year graduate students in the Biomedical Sciences Graduate Program and co-lectures a class in human genetics for medical students. Dr. Sander supervises postdoctoral fellows, graduate students, masters student, and undergraduate researchers in her laboratory. RESEARCH ACTIVITIES subjects have diabetes. To better understand the factors that contribute to the development of diabetes in the obese, Dr. Phillips has developed methods to study the hormonal activity of freshly isolated human fat tissue and cells over prolonged periods of time. Using this culture technique Dr. Phillips has worked to better understand the regulation of the insulin sensitizing in the obese are associated with reductions in the production of adiponectin by visceral (central) fat cells and that these fat cells are poorly responsive to currently available therapeutics. The cellular mechanisms responsible for synthesis and secretion of adiponectin are poorly understood. In recently published work Dr. Phillips reported that cellular obesity, hypertrophy, appears to contribute significantly to the low circulating levels of adiponectin in the obese. Ongoing studies are directed towards the identification of regulatory mechanisms that link cell size to adiponectin production. The ultimate goal of this work is to identify key regulatory steps in adiponectin synthesis and secretion for targeted therapeutic intervention to prevent obesity-related metabolic disease. Maike Sander, MD conducts research into developing strategies for a cell-based therapy for diabetes mellitus. The successful production of insulin-producing beta cells requires a thorough understanding of the molecular networks that direct the normal development of these cells. The main objective of Dr. Sander s current research is to identify strategies for producing functional insulin-producing beta cells from pluripotent stem cells in vitro. Research from her group established mechanisms by which cells activate the expression of important beta cell genes during development. Her work identified specific combinations of transcription factors that lead to the induction of pancreas and beta cell genes. These findings have important implications for the development of cell reprogramming strategies to produce beta cells from other cell sources in vitro. In recent work, Dr. Sander has also studied mechanisms of beta cell failure in type 2 diabetes. Work from her laboratory has identified important regulators of beta cell adaptation to increased nutrient load. She is current investigating whether these regulators could be targeted pharmacologically to improve glucose homeostasis in animal models of type 2 diabetes. Jianhua Shao, MD, PhD continues his researches in obesity. His laboratory currently is working on three main projects: 1) Adiponectin and fetal programming. The main goal of these studies is to elucidate the regulatory effects of adipocytesecreted hormone adiponectin in fetal growth and tissue development. 2) Placental lipid metabolism and fetal fat deposition. The objective of this study is to determine the Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 91

47 mechanisms underlying maternal obesity-induced fetal fat accumulation. Signaling pathways for controlling placental lipid metabolism and lipid transport are other main aims of this project. 3) Excessive gestational weight gain and longterm postpartum obesity. This project has successfully created a new rodent model resembling excessive gestational weight gain-associated long-term postpartum obesity in humans. These studies will identify a novel cause of obesity in women. The anticipated discovery of reprogramming of energy metabolism in adults is a significant breakthrough in obesity research. Maike Sander, MD conducts research into developing strategies for a cell-based therapy for diabetes mellitus. The successful production of insulin-producing beta cells requires a thorough understanding of the molecular networks that direct the normal development of these cells. The main objective of Dr. Sander s current research is to identify strategies for producing functional insulin-producing beta cells from pluripotent stem cells in vitro. Research from her group established mechanisms by which cells activate the expression of important beta cell genes during development. Her work identified specific combinations of transcription factors that lead to the induction of pancreas and beta cell genes. These findings have important implications for the development of cell reprogramming strategies to produce beta cells from other cell sources in vitro. In recent work, Dr. Sander has also studied mechanisms of beta cell failure in type 2 diabetes. Work from her laboratory has identified important regulators of beta cell adaptation to increased nutrient load. She is current investigating whether these regulators could be targeted pharmacologically to improve glucose homeostasis in animal models of type 2 diabetes. Jianhua Shao, MD, PhD continues his researches in obesity. His laboratory currently is working on three main projects: 1) Adiponectin and fetal programming. The main goal of these studies is to elucidate the regulatory effects of adipocytesecreted hormone adiponectin in fetal growth and tissue development. 2) Placental lipid metabolism and fetal fat deposition. The objective of this study is to determine the mechanisms underlying maternal obesity-induced fetal fat accumulation. Signaling pathways for controlling placental lipid metabolism and lipid transport are other main aims of this project. 3) Excessive gestational weight gain and longterm postpartum obesity. This project has successfully created a new rodent model resembling excessive gestational weight gain-associated long-term postpartum obesity in humans. These studies will identify a novel cause of obesity in women. The anticipated discovery of reprogramming of energy metabolism in adults is a significant breakthrough in obesity research. RESEARCH SUPPORT Michael Gottschalk, MD, PhD ITN (PI) 01/01/ /30/2014 $393,392 University of California San Francisco Effect of Antithymocyte Globulin on Preserving Beta-Cell Function in New-onset Type 1 Diabetes Mellitus (PI) 11/01/ /31/2017 $14,000 JAEB Center for Health Research T1D Exchange Clinic-based Registry (PI) 04/01/ /31/2014 $20,500 Sanford USD Medical Center Combination Therapy with Sitagliptin (DPP-4 Inhibitor) and Lansoprazole (Proton Pump Inhibitor) to Restore Pancreatic Beta Cell Function in Recent-Onset Type 1 Diabetes Mellitus George Washington University (PI) 04/01/ /31/2014 $9,000 TODAY Genetic Study Versartis (PI) 10/01/ /31/2017 $41,618 A Long-Acting Human Growth Hormone (VRS-317) in Prepubnertal Children with Growth Hormone Deficiency Eli Lilly and Company (PI) 04/01/ /30/2015 Safety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents with Type 2 Diabetes Protocol H8O-MC-GWBQ Andrew Hinton, PhD Hillbloom Foundation (PI) 07/01/ /30/2015 $63,636 MicroRNAs as Markers of Developmental Competency Toward Insulin Producing Cells Ulupi Jhala, PhD Juvenile Diabetes (PI) 07/01/ /30/2013 $93,130 Research Foundation Epigenetic Regulation of PDX1 Gene Hillbloom Foundation (PI) 07/01/ /30/2018 $90,909 Modeling Pancreatic Endocrine Cell Development Jane Kim, MD 1-14-IN-27 (PI) 01/01/ /31/2015 $100,000 American Diabetes Association Innovation Award Urinary Metabolomic Profiling in Children and Adults with Type 2 Diabetes DK (PI) 12/1/ /30/2015 $154,500 NIDDK Epigenetics of Obesity and Insulin Resistance Rady Children s Academic (PI) 05/01/ /31/2015 $50,000 Enrichment Fund The Metabolome in Obesity and Type 2 Diabetes UCSD Clinical & (PI) 05/01/ /30/2015 $50,000 Translational Research Institute Award Metabolomic Profiling in Children with Type 2 Diabetes and Obesity UCSD Pediatrics Genome (PI) 07/01/ /30/2015 $50,000 Research Project Epigenetic Predictors of Obesity and Insulin Resistance in Childhood Charles King, Ph.D. 2P01DK (PI) 04/01/ /30/2018 $90,000 NIH Spatio-temporal Regulation of PKA and PKC Signal Transduction 2014-D-005-NET (PI) 01/01/ /31/2018 $300,000 The Larry L. Hillblom Foundation Modeling Pancreatic Endocrine Cell Development Karen Klein, MD Pfizer Inc (PI) 11/01/ /31/2016 $69,470 Racial Diversity and Obesity Impact on Pubertal Onset Abbott (PI) 08/01/ /31/2013 $48,200 A Phase 3, Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy and Safety of Leuprolide Acetate mg and 30 mg Formulations in Children with Central Precocious Puberty Debiopharm Endo (PI) 07/01/ /30/2014 $18,820 Pharmaceuticals Inc. An Open-label Study on the Efficacy, Safety, and Pharmacokinetic of Triptorelinpamoate 22.5 mg 6-month Formulation in CPP Patients TOLMAR (PI) 09/01/2015-present An Open-label, Single Arm, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Leuprolide Acetate 45 mg for Injectable Suspension (6-month Formulation) in Subjects with Central (Gonadotropin-Dependent) Precocious Puberty (CPP) Ron Newfield, MD Bristol-Meyers Squibb (PI) 08/01/ /31/2015 $15,000 A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Saxagliptin (BMS ) as Monotherapy in Pediatric Patients with Type 2 Diabetes MK (PI) 10/01/2011-present $11,747 Merck A Study to Evaluate the Safety and Effectiveness of Sitagliptin in Treating Pediatric Patients with Type 2 Diabetes who have Inadequate Glycemic Control Protocol A (PI) 06/01/ /31/2014 Pfizer Non-Interventional (NI) Drug Study Protocol Quality of Life in Short Stature Youth Protocol MK (PI) 11/01/2013-present A Five-year, Observational, Non-interventional Follow-up to: A Phase III, Multicenter, Double-Blind, Randomized, Placebo- and Metformin-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control Protocol TRIALNET/University of Florida (PI) 05/01/2010-present Natural History Study of the Development of Type 1 Diabetes (TN- 01) Maike Sander, MD U01 DK (PI) 05/01/ /30/2020 $4,534,805 NIH/NIDDK Functional Analysis of T2D Associated Non-coding SNPs UC4 DK (PI) 09/01/ /30/2019 $3,913,839 NIH/NIDDK A 3-D Biomimetic Human Islet to Model Beta Cell Function in Health and Disease R21 CA (PI) 04/01/ /31/2017 $325,000 NIH/NCI A Novel Mouse Model to Identify Biomarkers of IPMN Formation and Progression R01 DK (PI) 09/01/ /30/2017 $1,609,300 NIH/NIDDK Mechanisms of Pancreatic Endocrine Cell Differentiation RB (PI) 04/01/ /31/2017 $1,050,300 CIRM Defining Links Between Chromatin State and Developmental Competence (PI) 08/01/ /01/2017 $692,219 Akros Pharma Inc Identification of Pharmacological Targets to Increase Beta Cell Mass R01DK (PI) 06/01/ /31/2016 $1,312,636 NIH/NIDDK Mechanisms of Pancreatic Beta Cell Specification 5 P30 DK (PI) 05/01/ /30/2018 $18,000 (Olefsky, PI) NIH/NIDDK Diabetes Research Center (DRC) U01 DK (PI) 09/01/ /30/2015 $4,784,000 NIH/NIDDK Epigenetic Strategies for the Generation of Replacement Beta Cells 1-SRA Q-R (PI) 11/01/ /31/2015 $146,552 JDRF The Proteome of Beta Cell Replication RB (PI) 11/01/ /31/2015 $1,400,000 CIRM Deciphering Transcriptional Control of Pancreatic Beta Cell Maturation in vitro 2012PG-T1D074 (PI) 04/01/ /31/2015 $200,000 The Leona M. & Harry B. Helmsley Charitable Trust Development of Enhancer Based Beta Cell Programming Strategies 2014PG-T1D047 (PI) 04/01/ /31/2015 $100,000 The Leona M. & Harry B. Helmsley Charitable Trust Increasing Pancreatic Beta Cell Mass: Characterizing a Novel Regulator of Beta Cell Proliferation 92 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 93

48 Jianhua Shao, MD, PhD 7 R01 DK (PI) 07/01/ /31/2013 $1,442,405 NIH (NIDDK) Adiponectin and Regulation of Triglyceride Metabolism American Diabetes Association (PI) 07/01/ /30/2012 $675,432 Transcriptional Regulation of Adiponectin Gene Expression PUBLICATIONS Al-Zubeidi H, Demeterco C, Jones KL. Thyrotoxic Hypokalemic Periodic Paralysis (THPP) in adolescents. Journal of Pediatric Endocrinology and Metabolism. 2014;28: Al-Zubeidi H, Gottschalk ME Newfield RS. Successful use of long acting octreotide in two cases with Beckwith-Wiedemann syndrome and severe hypoglycemia. Int J Pediatr Endocrinol. 2014;2014:18. Al-Zubeidi H, Klein KO. Randomized clinical trial evaluating metformin versus Oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome. J Pediatr Endocrinol Metab. 2015;28: Benitah SA, Bracken A, Dou Y, Huangfu D, Ivanova N, Koseki, H, Laurent, L, Limd DA. Meshorer E, Pombo A, Sander M, Xu GL. Stem cell epigenetics: looking forward. Cell Stem Cell. 2014;14: Bullinger M, Sommer R, Pleil A, Mauras N, Ross J, Newfield R, Silverman L, Rohenkohl A, Fox J, Quitmann J. Evaluation of the American-English Quality of Life in Short Stature Youth (QoLISSY) questionnaire in the United States. Health Qual Life Outcomes. 2015;13:43. Counts DR, Silverman LA, Rajicic N, Geffner ME, Newfield RS, Thornton P, Carakushansky M, Escobar O, Rapaport R, Levitsky L, Rotenstein D, Hey-Hadavi J, Wajnrajch MP. A 4-year, open-label, multicenter, randomized trial of genotropin growth hormone in patients with idiopathic short stature: Analysis of 4-year data comparing efficacy, efficiency, and safety between an individualized, target-driven regimen and standard dosing. Horm Res Paediatr. 2015;84: DeVas MG, Kopp JL, Heliot, C, Sander M, Cereghini S, Hautmaitre C. Hnf1b controls pancreas morphogenesis and generation of Ngn3+ endocrine progenitors. Development. 2015;142: Font-Burgada J, Shalapour S, Ramaswamy S, Hsueh B, Rossell D, Umemura A, Taniguchi K, Nakagawa H, Valasek M, Ye L, Kopp JL, Sander M, Carter H, Deisseroth K, Verma I, Karin M. Hybrid periportal hepatocytes regenerate the injured liver without giving Rise to cancer. Cell. 2015;162: Gitelman SE, Gottlieb PA, Rigby MR, Felner EI, Willi SM, Fisher LK, Moran A, Gottschalk M, Moore WV, Pinckney A, Keyes-Elstein L, Aggarwal S, Phippard Sayre PH, Ding L, Bluestone JA, Ehlers MR; START Study Team. Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2013;1: Griffin KJ, Thompson PA, Gottschalk M, Kyllo JH, Rabinovitch A. Combination therapy with sitagliptin and lansoprazole in patients with recent-onset type 1 diabetes (REPAIR-T1D): 12-month results of a multicentre, randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2013;2: Guo S, Dai C, Guo M, Taylor BL, Harmon J, Sander M, Robertson PR, Powers A, Stein R. MafA, MafB, Nkx6.1 and Pdx1 inactivation in type 2 diabetes. Journal of Clinical Investigation, 2013;123: Huang JS, Terrones L, Tompane T, Dillon L, Pian M, Gottschalk M, Norman GJ, Bartholomew LK. Preparing adolescents with chronic disease for transition to adult care: a technology program. Pediatrics. 2014;133:e Hendy GN, Canaff L, Newfield RS, Tripto-Shkolnik L, Wong BY, Lee BS, Cole DE. Codon Arg15 mutations of the AP2S1 gene: common occurrence in familial hypocalciuric hypercalcemia cases negative for calcium-sensing receptor (CASR) mutations. J Clin Endocrinol Metab. 2014;99:e Hinton A, Hunter SE, Afrikanova I, Jones GA, Lopez AD, Fogel GB, Hayek A, King CC. srna-seq analysis of human embryonic stem cells and definitive endoderm reveal differentially expressed micrornas and novel isomirs with distinct targets. Stem Cells. 2014;32: Humphrey RK, Ray A, Gonuguntla S, Hao E, Jhala US. Loss of TRB3 alters dynamics of MLK3-JNK signaling and inhibits cytokineactivated pancreatic beta cell death. J Biol Chem. 2014;289: Jin L, Feng T, Shih HP, Zerda R, Luo R, Hsu J, Mahdavi A, Sander M, Tirrell DA, Riggs AD, Ku TH. Colony-forming cells in the adult mouse pancreas are expandable in matrigel and form endocrine/ acinar colonies in laminin hydrogel. Proc Natl Acad Sci USA. 2013;110: Jörs S, Jeliazkova P, Ringelhan M, Thalhammer J, Du rl S, Ferrer J, Sander M, Heikenwalder M, Schmid RM, Siveke JT, Geisler F. Lineage fate of ductular reactions in liver injury and carcinogenesis. Journal of Clinical Investigation. 2015;125: Kanda S, Ohmori T, Taguchi A, Kudo K, Suzuki Y, Sato Y, Hino S, Sander M, Sugano S, Nakao M, Nishinakamura R. Sall1 maintains nephron progenitors and nascent nephrons by acting as both activator and a repressor. J Am Soc Nephrol. 2014;25: Kletter GB, Klein KO, Wong YY. A pediatrician's guide to central precocious puberty. Clin Pediatr. 2015;54: Klein KO. Is there a role for estrogen activity assays? Recombinant cell bioassay for estrogen: Development and applications. Steroids. 2015;99: Kopp JL, Sander M. New insights into the cell lineage of pancreatic ductal adenocarcinoma: evidence for tumor stem cells in premalignant lesions? Gastroenterology. 2014;146: Lee PA, Klein KO, Mauras N, Lev-Vaisler T, Bacher P. 36-month treatment experience of 2 doses of leuprolide acetate 3-month depot for children with central precocious puberty. J Clin Endocrinol Metab. 2014;99: Jain S, Sun X, Liu V, Sato YZ, Jimenez-Fernandez S, Newfield RS, Pourfarzib R, Tremoulet AH, Gordon JB, Daniels LB, Burns JC. Lipoprotein particle concentrations in children and adults following Kawasaki Disease. J Pediatr. 2014;165: Kolodziejczyk JK, Gutzmer K, Wright SM, Arredondo EM, Hill L, Patrick K, Huang JS, Gottschalk M, Norman GJ. Influence of specific individual and environmental variables on the relationship between body mass index and health-related quality of life in overweight and obese adolescents. Qual Life Res. 2015;24: Lancman JJ, Zvenigorodsky N, Gates KP, Zhang D, Solomon K, Humphrey RK, Kuo T, Setiawan L, Verkade H, Chi YI, Jhala US, Wright CV, Stainier DY, Dong PD. Specification of hepatopancreas progenitors in zebrafish by hnf1ba and wnt2bb. Development. 2013;140: Lim YH, Ovejero D, Sugarman JS, Deklotz CM, Maruri A, Eichenfield LF, Kelley PK, Ju ppner H, Gottschalk M, Tifft CJ, Gafni RI, Boyce AM, Cowen EW, Bhattacharyya N, Guthrie LC, Gahl WA, Golas G, Loring EC, Overton JD, Mane SM, Lifton RP, Levy ML, Collins MT, Choate KA. Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia. Hum Mol Genet. 2014;23: Lopez AD, Kayali AG, Hayek A, King CC. Isolation, culture, and imaging of human fetal pancreatic cell clusters. J Vis Exp. 2014;18 AWARDS Wenxian Fu, PhD Ray Thomas Edwards Foundation Career Development Recognition Award Helmholtz Young Investigator Diabetes Award Nominee, Nature Medicine 94 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 95

49 Gastroenterology, Hepatology & Nutrition 96 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 97

50 INTRODUCTION FACULTY The Division of Gastroenterology, Hepatology and Nutrition is dedicated to improving the lives of children and adolescents through outstanding clinical care, world renowned medical education, and cutting-edge research. Its clinical programs welcome a diverse patient population from not only Southern California but also from other nations including Mexico, Pacific Rim and Arab countries. The Division provides care to 12,000 outpatients and 4,500 inpatients each year, performing a total of 2,500 procedures a year. Patients come to the Division for knowledge, expertise and innovation. From creating new programs which address specific patient populations to conducting research on obesity and its metabolic complications, the Division is striving to be the best in the field. Over $3.2 million in research funding DIVISION FAST FACTS The Celiac Disease Clinic is 1 of just 5 clinics in the western United States Ariel Feldstein, MD Professor Division Chief Hannah Awai, MD Staff Physician Lars Bode, PhD Associate Professor in Residence Kerri Boutelle, PhD Professor of Clinical Pediatrics and Psychiatry in Residence Rebecca Cherry, MD Associate Clinical Professor MAJOR PLANS AND GOALS Lillian Choi, MD Associate Clinical Professor Ranjan Dohil, MD, BcH Professor of Clinical Pediatrics M. Abigail Garcia, MD Assistant Clinical Professor Nidhi Goyal, MD Staff Physician Xenia Hom, MD Associate Clinical Professor The Development of an Inflammatory Bowel Disease Center, a multidisciplinary center that will provide comprehensive care for children with Crohn s Disease and ulcerative colitis Recruitments are underway to support the capacity for research in developmental biology, stem cells, inflammatory bowel disease, and motility disorders To increase nutritional awareness by providing formal educational opportunities to the house staff and students. A Short Gut Pathway (Dr. Taylor) is near completion and will improve outcomes in hospitalized patients with intestinal failure. Also in development is an inpatient RCHSD Nutrition Support Team To enhance the fellowship program by maximizing the number of fellows, and seeking more GI-dedicated fellow training grant slots Jeannie Huang, MD, MPH Associate Professor in Residence Sherry Huang, MD Clinical Professor Assistant Dean, Graduate Medical Education Jae Kim, MD, PhD Clinical Professor Hayat Mousa, MD Professor of Clinical Pediatrics Clinical Medicial Director Kimberly Newton, MD Associate Clinical Professor 98 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 99

51 M. Paulina Ordonez, MD Assistant Adjunct Professor Dana Patton-Ku, MD Staff Physician Jeffrey Schwimmer, MD Professor of Clinical Pediatrics Warren Shapiro, MD Assistant Clinical Professor components: a multidisciplinary evaluation, a 12-week intervention group and individual therapies. The team addresses medical, developmental, behavioral and social- emotional aspects of feeding disorders in young children. The Intestinal Rehabilitation Center exclusively treats children suffering from short bowel syndrome, with the goal of improving nutrition status and weaning them of total parenteral nutrition (TPN). Neutrogatroenterology and Motility Center: The Center for Gastrointestinal Motility Disorders manages referrals with Hirschsprung s disease, pseudo obstruction, fecal incontinence, gastroparensis, abdominal pain, bloating, achalasia, feeding and swallowing disorders and severe constipation refractory to medical management. The Center also offers the following procedures: colonic motility studies, antroduodenal motility studies, anorectal motility studies, esophageal motility studies, smart pill, gastric emptying, gastric electric stimulation and sacral nerve stimulation. obesity through safe and personalized treatments. Our multidisciplinary team is dedicated to reducing the health burden of obesity in children, with a focus on reasonable and achievable goals. In 2001, the University of California, San Diego brought its established pediatric liver transplant program and renowned transplant team to Rady Children s in a combined effort to provide transplant patients in the region with the highest level of care. With UC San Diego s proven excellence in transplantation and Rady Children s nationally recognized treatment and healing environment, the two organizations have created a program that parallels the best in the United States. We have joined ImproveCareNow, a consortium of 85 centers in the US and UK who take care of children and adolescents with inflammatory bowel disease. With an emphasis on quality improvement, the network s goal is to increase the percentage of patients in sustained and steroid-free remission. The Weight and Wellness Center manages child and adolescent Mamata Sivagnanam, MD Assistant Professor in Residence Tamara Taketani, MD Assistant Professor Jonathan Africa, MD, year, UCSD Kathryn Harlow, MD, year, UCSD Maheen Hassan, MD, year, UCSD The board-certified faculty members of the Division of Gastroenterology and Nutrition are the sole providers for pediatric digestive diseases in San Diego and Imperial Counties, providing consultations for patients and physicians on all aspects of gastrointestinal disease in the inpatient and outpatient setting, including diagnostic and therapeutic endoscopies, living-related and cadaveric liver transplantation, liver diseases, obesity, wellness and nutrition, eosinophilic esophagitis, motility disorders, parenteral and enteral nutritional supplementation, and disorders of the pancreas and gallbladder. The Division has outpatient clinic centers at Rady Children s Hospital-San Diego (RCHSD), Balboa Naval Medical Center, and Kaiser-Permanente. The Division also provides outpatient satellite care in Escondido, Murrieta, and Encinitas. The Celiac Disease Clinic diagnoses celiac disease in children and provides follow-up care to ensure they are sticking to a gluten-free diet. Affected children and their families are referred to a celiac disease nutritionist for nutritional counseling and medical nutrition therapy services, and the child s growth and other nutritional 100 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Sharon Taylor, MD Clinical Professor FELLOWS Elizabeth Yu, MD Assistant Professor Lourdes Herrera, MD, year, UCSD Amber Hildreth, MD, year, UCSD CLINICAL ACTIVITIES parameters are monitored over time. To better care for our cystic fibrosis patients, we developed the Cystic Fibrosis/Gastroenterology Clinic, a multidisciplinary clinic that involves gastroenterology, pulmonology, nutrition, respiratory therapy, social work and cystic fibrosis nursing care. We offer comprehensive care for children diagnosed with eosinophilic esophagitis in our Eosinophilic Gastrointestinal Disorders Clinic which is staffed by a multidisciplinary team of pediatric allergists/immunologists, a pediatric gastroenterologist, a pediatric nutritionist and a pediatric nurse coordinator. The Fatty Liver Clinic was the first of its kind in the country to care for children and adolescents with fatty liver disorders. Out stateof-the-art care is complemented by an active research program on obesity and fatty liver disease. The Feeding Team at Rady Children s Hospital has three The Division s ACGME accredited three-year fellowship program trains up to six fellows in clinical and basic science research. The program combines clinical and research training throughout the program, with the first year focused on an in-depth clinical experience in gastroenterology, hepatology, and nutrition. The second and third years provide time for focused development of research interests. In addition to the fellowship, our division provides training and elective opportunities to medical students at all levels, as well as pediatric residents. Jeannie Huang, MD, MPH, Director of Continuing Medical Education at Rady Children's Hospital, has also been and currently is involved in a number of national medical education efforts, including the award-winning Health and Obesity: Prevention and Kerri Boutelle, PhD performs research focusing on the causes, characterization, prevention and treatment of childhood, adolescent and adult obesity and eating disorders. Overarching research objectives include investigating the role of familial factors in the etiology, prevention, and treatment of obesity and eating disorders in youth, utilizing principles of basic behavioral science to inform and improve treatments for obesity and eating disorders; and determining intervention and prevention strategies aimed at changing the trajectory of weight and eating disorders in children and adolescents. In ongoing studies, Dr. Boutelle hopes to identify innovative and cost- effective treatment strategies for obese children (parent-only treatments), to develop new treatments based on basic behavioral research for children who binge eat (self-regulation treatments), and to disseminate current behavioral treatment through innovative methods (guided self-help, computer-based guidance for primary care physicians). Dr. Boutelle s clinical interests lie in the treatment of childhood and adolescent obesity and eating disorders, and the concomitant depression, anxiety, oppositional, personality, behavioral and family changes that occur with eatingrelated difficulties. Her clinical work is grounded in empirically based cognitive-behavioral, interpersonal and family-based treatments, and she provides and supervises individual, group and family therapy. Rebecca Cherry, MD, MPH, is the Associate Director of the Motility Center at RCHSD, providing consultation and diagnostic procedures for children with GI dysmotility as well as persistent abdominal TEACHING ACTIVITIES Education project. She is the Chair of the NASPGHAN Maintenance of Certification Task Force and currently leads a number of national quality improvement projects targeting both clinical and procedural issues. Sherry Huang, MD recently became the Associate Dean and Designated Institutional Official for UC San Diego School of Medicine. In her role as the Associate Dean for Graduate Medical Education, Dr. Huang has developed educational activities for the institution in the areas of quality improvement and patient safety and resident well-being in alignment with the ACGME standards for the Clinical Learning Environment. She serves as a committee member for educational committees at the School of Medicine (committee for Educational Policies, the Health Sciences Faculty Council, and review committee for medical student admissions). RESEARCH ACTIVITIES pain. She is also leads RCHSD s involvement in ImproveCareNow, an international consortium of pediatric medical centers working to improve quality of care and establish best practices for children and adolescents with inflammatory bowel disease. Dr. Cherry has a particular interest in the overlap between inflammatory and functional gastrointestinal disorders, and is actively collaborating with the UCSD Center for Mindfulness to develop mind-body programs for patients with chronic abdominal pain. She is also studying the use of oral viscous budesonide for symptomatic and histologic improvement in patients with eosinophilic esophagitis. Lillian Choi, MD has special interests in pediatric gastroenterology that include functional abdominal pain. She was an active co-investigator of a pilot open-labeled trial investigating the effectiveness of SAM-e for the treatment of Functional Abdominal Pain (FAP) in children. Dr. Choi is also the Director of Endoscopy. Her goals are to maximize quality and patient safety. This includes regularly updating the endoscopy suite in regards to the latest endoscopic technologies and procedural equipment, and to expand the repertoire of endoscopic procedures available to patients which will allow for more efficient, more therapeutic, and most importantly, more reliable and safer care for patients. She has instituted regular and iterative quality improvement evaluations regarding the procedural service to ensure excellent patient care and comfort Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 101

52 Ranjan Dohil, MD's research interest has included eosinophilic esophagitis in childhood and gastrointestinal manifestations of cystinosis. He has been awarded grants from the Hearst and the Cystinosis Research Foundation which have allowed him to study different aspects of these diseases. Data accrued from studies of the pharmacokinetics and pharmacodynamics of cysteamine bitartrate in children with cystinosis were used to develop a new formulation of cysteamine which patients could tolerate better (fewer GI symptoms) and required twice-daily rather than every 6 hour ingestion. On April 2013 the new delayed and extended-release formulation of cysteamine (RP103 or ProcystbiTM), developed at UCSD along with Raptor Pharmaceuticals, was FDA approved and will now be commercially available for the treatment of cystinosis. The new drug has already been shown in the long-term studies to improve the quality of life for many of these patients. An article about the development of Procysbi was recently published in the New York Times. Following the development of RP103 a number of multicenter studies have been started using this drug in the treatment of NAFLD and Huntington s disease. Ariel Feldstein, MD is Chief of the Division. He is regarded as a leading physician scientist in the field of Pediatric Hepatology. Dr. Feldstein s research program is focused on dissecting the biochemical pathways of cell death trigger by over-accumulation of fatty acids and other lipids in the liver and other organs, which may play an important role in disease processes such as obesityassociated liver disease (nonalcoholic steatohepatitis or NASH), and type 2 diabetes. A second objective is to better understand the events that link excessive accumulation of lipids in the liver (steatosis) to liver injury, fibrosis and carcinogenesis. His research is currently supported by several grants from the National Institutes of Health (NIH) as well as foundation and industry grants. His laboratory has provided key evidence to support the currently most accepted theory of the role of hepatic lipid compartmentation and lipotoxicity in the pathogenesis of steatohepatitis development. Most recently, he provided key evidence for a novel pathogenic role for NLR Inflammasomes, and in particular NLRP3 in liver inflammation and fibrosis. Moreover, he is working to discover novel therapies and non-invasive biomarkers for early diagnosis and monitoring of liver damage and fibrosis. His lab has established cell-free systems, cell culture systems, precision-cut liver slices and murine models of steatohepatitis to tests novel therapies including small molecules, and RNAi technology. They also utilize an array mass spectrometrybased approaches (LC/ESI/MS/MS, proteomics) directed toward identifying novel mechanism based biomarkers. The goal is to use these discoveries to develop safe and efficacious diagnostics and therapeutic strategies for patients with these highly prevalent and potentially serious conditions. To this end, Dr. Feldstein is actively involved in the development of preclinical, translational and clinical research protocols for a number of non-invasive tests and therapeutic agents. Dr. Feldstein s lab offers a unique environment for fellows in the gastroenterology training program combining significant clinical and translational endeavors with substantial basic research opportunities. M. Abigail Garcia, MD receives funding from the Cystic Fibrosis Foundation to research gastrointestinal manifestations of cystic fibrosis. Dr. Garcia focuses on understanding the pathophysiological basis of cystic fibrosis (CF). Her research aims to understand the consequences of diminished bicarbonate transport in CF and how this affects development of mucoviscidosis. She has shown that bicarbonate is essential for optimal mucus secretion in mouse models, and that bicarbonate deficiency inhibits intestinal mucus release. She is further investigating the mechanisms behind this finding to provide an effective treatment option to CF patients who suffer from distal intestinal obstruction syndrome or chronic constipation. Jeannie Huang, MD, MPH is a member of the Center for Wireless & Population Health Systems - a body of investigators whose work focuses on the creative use of networked technologies and ubiquitous computing to improve population health (cwphs. ucsd.edu). Dr. Huang has led several highly innovative health intervention projects addressing personal health behaviors and public health issues, including Texting to promote Adolescent Health Liaisons and Communication (TAHLC), a technology-based intervention for adolescents with chronic disease that significantly increased health-related self-efficacy and healthcare engagement among adolescents with chronic disease during preparation for their transition to adult care; Fit4Life, a successful technology-based weight management program among children who have survived acute lymphoblastic leukemia; and SMART: A Social and Mobile Weight Control Program for Young Adults, that utilized multiple technology platforms to deliver a weight management program to obese young adults. Dr. Huang also is PI of a state-of-the-art NIH-funded project with Dr. Bartlett in the School of Engineering using facial recognition and other sensor technologies to evaluate pain expressions in children with clinical pain. She is also a coinvestigator in two NSF-funded projects evaluating how cloud data processing may be used to provide real-time clinical feedback for real world health sensor data. Finally, she is an active member of a NIH-funded project evaluating privacy issues related to use of personal medical data. Sherry Huang, MD is involved in studies of kindreds with early colon cancer risk, with particular interest in patients with hamartomatous polyposis syndromes. She is involved in research evaluating the genetics of early colon cancer in children and its pathogenesis. Her projects involve the role the oncogene PTEN plays in relation to DNA mismatch repair. She also has projects looking at activation of Wnt Signaling in hamartomatous polyposis. Dr. Huang also studies the AKT pathway in hamartomaotus polyps with special focus on mtor signaling. Dr. Huang s clinical focus is on the early detection of colon cancer and at-risk kindreds. Working with geneticists from UCSD Moores Cancer Center, Dr. Huang evaluates and counsels kindreds at risk for colon cancer. Hayat Mousa, MD, a leading expert in pediatric motility disorders, Dr. Mousa s key interests include swallowing disorders, gastroparesis, gastric electric stimulation, constipation, cecostomy, sacral nerve stimulation, rumination, gastroesophageal reflux, gastrointestinal motility and functional disorders. Dr. Mousa received an NIH funds and established the normal values for non-acid gastroesophageal reflux in children. She is widely published on numerous research studies and clinical trials. Some notable studies include: gastric pacemaker therapy for gastroparesis; health consequences of sleep disorders in obese children and its association with gastroesophageal reflux disease; acid and non-acid gastroesophageal reflux in children; effect of fundoplication on gastric sensory and motor functions; value of colonic motility in predicting the outcome of cecostomy placement in patients with severe constipation; prospective studies to evaluate the difference between constipated children with or without lower urinary symptoms and comparing the ambulatory and stationary colonic manometry techniques. Dr. Mousa frequently presents nationally and internationally on topics related to diagnosing and treating pediatric motility disorders. Kimberly Newton, MD, serves as the Director of the Celiac Disease Clinic at RCHSD. This clinic is one of fewer than 5 clinics in the western United States dedicated to the diagnosis and treatment of celiac disease in children. Once diagnosed, children are followed closely to ensure adaptation and adherence to the glutenfree diet, and to monitor growth and other nutritional parameters over time. The clinic currently cares for over 220 children with celiac disease. Dr. Newton has recently participated in a national working group, which is currently developing Best Practices expert consensus statement pertaining to management of celiac disease in children. She has also been actively engaged in numerous outreach and educational activities related to celiac disease. In addition to celiac disease, Dr. Newton s clinical focus has broadened to include hepatology, and she is currently the Interim Medical Director of the Pediatric Liver Transplant Program at RCHSD, and is also coinvestigator in several clinical research studies investigating pediatric nonalcoholic fatty liver disease. Jeffrey Schwimmer, MD is Director of the Weight and Wellness Center, a multi-disciplinary program for the evaluation and treatment child and adolescent obesity at RCHSD. Dr. Schwimmer s research emphasis is on the complications of obesity, both metabolic and behavioral. Dr. Schwimmer also Director of the Fatty Liver Clinic at RCHSD, the first clinic in the U.S. dedicated to the care of children with fatty liver disease. Fatty liver is now the most common cause of chronic liver disease in children. Dr. Schwimmer s research includes the development and validation of non-invasive imaging for diagnosis, clinical trials for the treatment of steatohepatitis in children, and the role of the intestinal microbial environment in susceptibility to fatty liver. Warren Shapiro, MD continues to be interested in functional GI disorders. He implemented a GI Biofeedback Clinic at Kaiser, which has had significant success in helping the difficult cases. He inaugurated a similar clinic at RCHSD. Mamata Sivagnanam, MD research focuses on congenital tufting enteropathy. This is a severe and life- threatening problem presenting with intractable diarrhea in infancy. Using modern genetic technology, Dr. Sivagnanam isolated epithelial cell adhesion molecule (EpCAM) as a gene associated responsible for this condition. She focuses on the effect it has on intestinal epithelial physiology. She is working to gain a better understanding of the role of adhesion molecules in intestinal epithelial development in health and disease. Dr. Sivagnanam also has interest in how foods supplements and therapies alter the intestinal barrier and its functions. Sharon Taylor, MD is Director of Nutrition Support Services. She runs the Intestinal Rehabilitation clinic, managing most of the complex short bowel pediatric population in San Diego. She is responsible for RCHSD Nutrition Manual and Guidelines. Elizabeth L. Yu, MD completed her pediatric GI fellowship at Rady Children s hospital/ucsd ( 12) and joined the GI division. Her prior research focused on Histone deacetylase inhibitor (HDACi) mediated hepato-protective effects on nonalcoholic steatohepatitis (NASH) and attenuation of obesity-induced metabolic dysfunction. As current therapy for NASH is lifestyle modification through diet and exercise, the eventual goal is to have a clinical application for HDACis in treatment of NASH. She is currently transitioning to translational research in NASH. PUBLICATIONS Eguchi A and Feldstein AE. Lysosomal Cathepsin D contributes to cell death during adipocyte hypertrophy. Adipocyte 2013;2: Giannini C, Feldstein AE, Santoro N, Kim G, Kursawe R, Pierpont B, Caprio S. Circulating levels of FGF-21 in obese youth: associations with liver fat content and markers of liver damage. J Clin Endocrinol Metab 2013;98: Feldstein AE, Alkhouri N, De Vito R, Alisi A, Lopez R, Nobili V. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. Am J Gastroenterol 2013;108: Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein AE. From NAFLD to NASH to cirrhosis - new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol 2013;10: Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, Hoffman HM, Feldstein AE. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation and fibrosis. Hepatology 2014;59: Santoro N, Caprio S, Feldstein AE. Oxidized metabolites of linoleic acid as biomarkers of liver injury in NASH. Clin Lipidol 2013;8: Hillian AD, McMullen MR, Sebastian BM, Rowchowdhury S, Kashyap SR, Schauer PR, Kirwan JP, Feldstein AE, Nagy LE. Mice lacking C1q are protected from high-fat diet-induced hepatic insulin resistance and impaired glucose homeostasis. J Biol Chem 2013;288: Gulati R, Radhakrishnan KR, Hupertz V, Wyllie R, Alkhouri N, Worley S, Feldstein AE. Health related quality of life in children with autoimmune liver disease. J Pediatr Gastroenterol Nutr 2013;57: Ramsden C, Faurot K, Zamora D, Suchindran CM, MacIntosh BA, Gaylord S, Ringel A, Hibbeln JR, Feldstein AE, Mori TA, Barden A, Lynch C, Coble R, Mas E, Palsson O, Barrow DA, Mann JD. Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial. PAIN 2013;154: Povero D, Eguchi A, Niesman IG, Andronikou N, de Mollerat X, Mulya A, Berk M, Lazic M, Thapaliya S, Parola M, Patel P, Feldstein AE. Lipid-induced toxicity stimulates hepatocytes to release angiogenic microparticles that require Vanin-1 for uptake by endothelial cells. Science Signal 2013;6:ra88. Patel NS, Peterson MR, Lin GY, Feldstein A, Schnabl B, Bettencourt R, Seki E, Sirlin CB, Loomba R. Insulin resistance increases MRIestimated pancreatic fat in nonalcoholic fatty liver disease and normal controls. Gastroenterol Res Pract 2013;2013: Choi LJ, Huang JS. A pilot study of S-adenosyl-methionine in treatment of functional abdominal pain in children. Altern Health and Med 2013;19: Eguchi A, Feldstein AE. Lysosomal Cathepsin D contributes to cell death during adipocyte hypertrophy. Adipocyte 2013;2: Huang JS, Barlow SE, Quiros-Tejeira RE, Scheimann A, Skelton J, Suskind D, Tsai P, Uko V, Warolin JP, Xanthakos SA: The NASPGHAN obesity task force. Consensus statement: childhood obesity for pediatric gastroenterologists. J Pediatr Gastroenterol Nutr 2013; 56: Teich S, Mousa HM, Punati J, Di Lorenzo C. Efficacy of permanent gastric electrical stimulation for the treatment of gastroparesis and functional dyspepsia in children and adolescents. J Pediatr Surg 2013; 48: Machado R, Woodley FW, Skaggs B, Di Lorenzo C, Splaingard M, Mousa H. Gastroesophageal reflux causing sleep interruptions in infants. J Pediatr Gastroenterol Nutr 2013; 56: Green AD, Belkind-Gerson J, Surjanhata BC, Mousa H, Kuo B, Di Lorenzo C. Wireless motility capsule test in children with upper gastrointestinal symptoms. J Pediatrics 2013;162: Lu PL, Teich S, Di Lorenzo C, Skaggs B, Alhajj M, Mousa HM. Improvement of quality of life and symptoms after gastric electrical stimulation in children with functional dyspepsia. Neurogastroenterology 2013; 25:567-e456. Mugie SM, Perez ME, Burgers R, Hingsbergen EA, Punati J, Mousa H, Benninga MA, Lorenzo CD. Colonic manometry and colonic scintigraphy as a diagnostic tool for children with severe constipation. J Pediatr Gastroenterol Nutr 2013; 57: Schwimmer JB. Clinical trials for adolescent obesity: Cooking up an alphabet stew of what to do. In: JAMA Pediatrics 2013;167: Swiderska-Syn M, Suzuki A, Guy CD, Schwimmer JB, Abdelmalek MF, Lavine JE, Diehl AM. Hedgehog pathway and pediatric nonalcoholic fatty liver disease. Hepatology 2013;57: Tompane TM, Bush R, Dansky T, Huang JS. Diagnostic imaging studies performed in children over a nine-year period. Pediatrics. 2013;131:e Yang N, Garcia MA, Quinton PM. Normal mucus formation requires camp-dependent HCO3- secretion and Ca2+- mediated mucin exocytosis. J Physiol 2013;591: Santoro N, Caprio S, Giannini C, Kim G, Kursawe R, Pierpont B, Shaw MM, Feldstein AE. Oxidized fatty acids: A potential pathogenic link between fatty liver and type 2 diabetes in obese adolescents. Antioxid Redox Signal 2014;10: Cusi K, Chang Z, Harrison S, Lomonaco R, Bril F, Orsak B, Ortiz- 102 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 103

53 Lopez C, Hecht J, Feldstein AE, Webb A, Louden C, Goros M, Tio F. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). J Hepatol 2014;60: Feldstein AE, Patton-Ku D, Boutelle KN. Obesity, nutrition, and liver disease in children. Clin Liver Dis 2014;18: Masuda T, Fu Y, Eguchi A, Czogalla J, Rose MA, Kuczkowski A, Gerasimova M, Feldstein AE, Scadeng M, Vallon V. Dipeptidyl peptidase-4 inhibitor lowers PPARγ agonist-induced body weight gain by affecting food intake, fat mass and beige/brown fat but not fluid retention. Am J Physiol Endocrinol Metab 2014;306: Eguchi A, Wree A, and Feldstein AE. Biomarkers of liver cell death. J Hepatol 2014;60: Alkhouri N, Berk M, Yerian L, Lopez R, Chung YM, Zhang R, McIntyre TM, Feldstein AE, Hazen SL. OxNASH score correlates with histologic features and severity of nonalcoholic fatty liver disease. Dig Dis Sci 2014;59: Navaneethan U, Gutierrez NG, Venkatesh PG, Jegadeesan R, Zhang R, Jang S, Sanaka MR, Vargo JJ, Parsi MA, Feldstein AE, Stevens T. Lipidomic profiling of bile in distinguishing benign from malignant biliary strictures: A single-blinded pilot study. Am J Gastroenterol 2014;109: Thapaliya S, Wree A, Povero D, Inzaugarat ME, Berk M, Dixon L, Papouchado BG, Feldstein AE. Caspase 3 inactivation protects against hepatic cell death and ameliorates fibrogenesis in a diet induced NASH model. Dig Dis Sci 2014;59: Eguchi A, Feldstein AE. Adipocyte cell death, fatty liver disease and associated metabolic disorders. Dig Dis 2014;32: Aytekin M, Tonelli AR, Farver CF, Feldstein AE, Dweik RA. Leptin deficiency recapitulates the histological features of pulmonary arterial hypertension in mice. Int J Clin Exp Pathol 2014;7: Lazic M, Eguchi A, Berk MP, Povero D, Papouchado B, Mulya A, Johnson CD, Feldstein AE. Differential regulation of inflammation and apoptosis in Fas-resistant hepatocyte-specific Bid-deficient mice. J Hepatol 2014;61: Wree A, McGeough MD, Peña CA, Schlattjan M, Li H, Inzaugarat ME, Messer K, Canbay A, Hoffman HM, Feldstein AE. NLRP3 inflammasome activation is required for fibrosis development in NAFLD. J Mol Med (Berl) 2014;92: Lazic M, Inzaugarat E, Povero D, Chen I, Chen M, Nalbandyan M, Miller YI, Cherñavsky AC, Feldstein AE, Sears DD. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis. PLoS One 2014;9:e Wree A, Schlattjan M, Bechmann LP, Claudel T, Sowa JP, Stojakovic T, Scharnagl H, Köfeler H, Baba HA, Gerken G, Feldstein AE, Trauner M, Canbay A. Adipocyte cell size, free fatty acids and apolipoproteins are associated with non-alcoholic liver injury progression in severely obese patients. Metabolism 2014;63: Povero D, Eguchi A, Li H, Johnson CD, Papouchado BG, Wree A, Messer K, Feldstein AE. Circulating extracellular vesicles with specific proteome and liver micrornas are potential biomarkers for liver injury in experimental fatty liver disease. PLoS One 2014;9:e Woodley FW, Machado RS, Hayes D Jr, Di Lorenzo C, Kaul A, Skaggs B, McCoy K, Patel A, Mousa H. Children with cystic fibrosis have prolonged chemical clearance of acid reflux compared to symptomatic children without cystic fibrosis. Dig Dis Sci 2014; 59: Scholes MA, McEvoy T, Mousa H, Wiet GJ. Cricopharyngeal achalasia in children: botulinum toxin injection as a tool for diagnosis and treatment. The Laryngoscope 2014; 124: Mousa HM, Montgomery M, Alioto A. Adolescent rumination syndrome. Curr Gastroenterol Rep 2014;16:398. Mousa H, Machado R, Orsi M, Chao CS, Alhajj T, Alhajj M, Port C, Skaggs B, Woodley FW. Combined multichannel intraluminal impedance-ph (MII-pH): multicenter report of normal values from 117 children. Curr Gastroenterol Rep 2014;16:400. Liem O, Burgers RE, Connor FL, Benninga MA, Mousa HM. Prolonged colonic manometry in children with defecatory disorders. J Pediatr Gastroenterol Nutr 2014; 59: Mueller JL, McGeough MD, Pena CA, Sivagnanam M. Functional Consequences of EpCAM mutation in mice and men. Am J Physiol Gastrointest Liver Physiol 2014;306:G Liu H, Beier J, Arteel G, Ramsden C, Feldstein AE, McClain CJ, Kirpich IA. Transient Receptor Potential Vanilloid 1 Gene deficiency ameliorates hepatic injury in a mouse model of chronic-bingeinduced alcoholic liver disease. Am J Pathol 2015;185: Navarro LA, Wree A, Povero D, Berk M, Ghosh S, Papouchado BG, Erzurum SC, Feldstein AE. Arginase 2 dificiency results in spontaneous steatohepatitis: A novel link between innate immune activation and hepatic de novo lipogenesis. J Hepatol 2015;62: Mugie SM, Bates DG, Punati JB, Benninga MA, Di Lorenzo C, Mousa HM. The value of fluoroscopic defecography in the diagnostic and therapeutic management of defecation disorders in children. Pediatr Radiol 2015;45: Woodley FW, Machado R, Di Lorenzo C, Mousa H. Chemical clearance in infants and children with acid reflux in the physiologic range. J Pediatr Gastroenterol Nutr 2015;60: Sulkowski JP, Nacion KM, Deans KJ, Minneci PC, Levitt MA, Mousa HM, Alpert SA, Teich S. Sacral nerve stimulation: a promising therapy for fecal and urinary incontinence and constipation in children. J Pediatr Surg 2015; 50: Kozan P, McGeough MD, Pena CA, Mueller JL, Barrett K, Marchelletta R, Sivagnanam M. Mutation of EpCAM leads to intestinal barrier and ion transport dysfunction. J Mol Med (Berl) 2015;93: BOOK CHAPTERS Cherry R. Failure to thrive. Chapter 12; in Pediatric Gastrointestinal and Liver Disease, 5th edition. Ed. Robert Wyllie, Jeffrey Hyams, and Marsha Kay. Philadelphia, Elsevier (2015). Sivagnanam M, Janecke AR, Mu ller T, Heinz-Erian P, Taylor S, Bird LM. Case of syndromic tufting enteropathy harbors SPINT2 mutation seen in congenital sodium diarrhea. Sivagnanam M, Janecke AR, Mu ller T, Heinz-Erian P, Taylor S, Bird LM. 6. AWARDS AND HONORS Lars Bode, PhD Received the Norman Kretchmer Memorial Award in Nutrition and Development from the American Society for Nutrition Received the 2012 Ehrlich-Koldovsky Award from the International Society for Research in Human Milk and Lactation President-Elect International Society for Research in Human Milk and Lactation Editorial Board member - Advances in Nutrition Jeannie Huang, MD, MPH Recipient, Learning! 100 Award, The Health Professional Obesity: Prevention & Education (HOPE) Project, 2012 Inaugural Recipient, Teri Li Education Award, NASPGHAN, 2012 Selected, Best Doctors in America, Hayat Mousa, MD NASPGHAN Motility Prize AAMC Mid-Career Women Faculty Professional Listed, Best Doctors in America Listed, America's Top Physicians Nationwide Children Hospital Career Contribution Award NCH IMPACT Business Process Improvement Program Award: Faculty Advancement, Mentoring and Engagement (FAME) Scholarship RESEARCH SUPPORT Kerri Boutelle, PhD 1R01DK (PI) Jul 2010-June 2015 $402,886 NIH/ NIDDK Parents as the Agent of Change for Childhood Obesity 1R01DK (PI) April 2012-March 2017 $359,469 NIH/ NIDDK Learning Theory to Improve Obesity Treatments K02HL (PI) April 2012-March 2017 $98,926 The Treatment of Childhood Obesity NIH/NCI (PI Marshall) June 2013-May 2018 $499,999 Text Messaging Intervention to Impact Weight Loss among Overweight & Obese Youth Pending (PI) Sept 2013-Aug 2014 $90,000 USDA/Egg Nutrition Center Pending Rebecca Cherry, MD (PI) July 2010-July 2011 $50,000 Pilot Study of Esophageal Dysmotility in Eosinophilic Esophagitis UCSD Department of Pediatrics Intramural Clinical Research Grant (PI) July 2011-July 2012 $17,500 Pilot Study of Clinical Hypnosis for Treatment of Abdominal Pain in Children UCSD Academy of Clinical Scholars/STRI Faculty Research Award NCT (PI) July 2012-June 2014 Pharma, Inc. Oral Budesonide Suspension (OBS) in Adolescent and Young Adult Subjects (12-25 Years of Age) With Eosinophilic Esophagitis: A Phase II, Randomized, Double-blind, Placebo-Controlled Study with an Open-Label Extension Meritage Ranjan Dohil, MB, BCh (PI) Mar 2006-Oct 2012 $458,814 Cystinosis Research Foundation Treatment of Cystinosis with EC-Cysteamine (PI) Oct 2008-Sept 2011 $271,691 Cystinosis Research Foundation Various Studies in Cystinosis (PI) Oct 2011-Sept 2013 $194,250 Cystinosis Research Foundation Two year funding proposal for Betty Cabrera, BS, MPH (PI) Sept 2011-Sept 2012 $120,000 Raptor Pharmaceutical Corp Food-Effect on Bioavailability of Cystagon8482 in Normal, Healthy Adults Ariel Feldstein, MD U01 AA (PI) Jul 2014-June 2019 Oxidized Metabolites of Linoleic Acid in Alcohol-induced Liver Injury R21AA (PI) Sept 2015-Aug 2017 NIH/NIAAA Encapsulated RNAs in Extracellular Vesicles Contribute ALD Progression T32 DK07202 (PI Crowe) Dec 2011-Nov 2016 NIH/NIDDK Gastroenterology Training Grant Representative research training program in Pediatric GI Gilead Sciences, Inc. (PI) June 2015-May 2017 Circulating Extracellular vesicles as Biomarkers in NASH Gilead Sciences, Inc. (PI) Aug 2015-July 2017 Preclinical studies on the effects of the ASK1 inhibitor GS-4997 on genetic and dietary models of steatohepatitis Conatus Pharmaceutical (PI) Sept 2014-Mar 2016 Preclinical Studies on the effects of the pan caspase inhibitor IDN on models of portal hypertension Conatus Pharmaceutical (PI) July 2015-June 2016 Effects of Emricasan on Circulating Extracellular Vesicles (EVs) in Subjects with Mild, Moderate and Severe Hepatic Impairment (PI Eguchi) Jan 2014-Jan 2016 Gilead/Research Scholar Award Role: Mentor Adipocyte-derived microparticles in the initiation of adipose tissue inflammation during weight gain (PI) Hepatocyte-derived microparticles as pro-fibrogenic modulators and potential biomarkers for early diagnosis and therapy of NAFLD and NASH American Liver Foundation (ALF) / Roger L. Jenkins, MD Jan 2014-June 2015 Postdoctoral Research Fellowship Award (POVERO) Role: Mentor Jeannie Huang, MD 1 RC1 MD (PI) Sept 2009-July 2012 $999,891 NIH (NCMHD) TAHLC: Texting to Promote Adolescent Health Liaisons and Chronic Disease Management MRSG (PI) July 2007-June 2013 $583,200 CPPB/American Cancer Soc, Inc. PACE-CALL: A Tailored Weight Management Program for Childhood ALL Survivors NIH/NCI U01 (PI Patrick) $2,277,572 Social and Mobile Weight Control Intervention for Young Adults CalIT2 Strategic Research (PI) $32,878 Opportunities Program Automatic Facial Expression analysis for Measurement of Pain and Stress, NIH/NINR (Co-PI with Dr. Bartlett) $2,609,392 Development of a New Technology for Assessing Pediatric Pain (NTAP) (PI Patrick) $2,000,000 DELPHI: Data E-platform Leveraged for Patient Empowerment and Population Health Improvement NSF CTRI/Intramural (PI) $33,000 Neurobiology of Pain Processing in Children with Gastrointestinal Disorders 104 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 105

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54 NSF (PI Tilak) $617,681 SenseHealth: A Platform to Enable Personalized Healthcare through Context-aware Sensing and Predictive Modeling Using Sensor Streams and Electronic Medical Record Data Hayat Mousa, MD ANM1 502 (PI) July 2015-June 2017 $128,000 Abbott Nutrition 2 Fucosyllactose and Gut Motility in Human Subjects T32 DK07202 (PI Crowe) Dec 2011-Nov 2016 NIH/NIDDK Gastroenterology Training Grant Role: Representative research training program in Pediatric GI UCSD Academic Enrichment Fund (PI) July 2015-June 2017 $80,000 UCSD Faculty Bridge Fund (PI) July 2015-June 2018 $150,000 5T32 DK (PI) July 2015-June 2017 Esophageal distensibility: its value in predicting fibrotic remodeling and clinical phenotype in patients with eosinophilic esophagitis (PI) Oct 2010-Sept 2014 $158,980 "A randomized controlled trial of amitriptyline for chronic oral food refusal" (PI Team: Ann McGrath Davis, PhD, MPH, Amanda Bruce, PhD, Hayat Mousa, MD, Paul Hyman, MD) (PI) American Neurogastroenterology and Motility Society July Dec 2015 Educational grant to train gastroenterology fellows in pediatric motility. Jeffrey Schwimmer, MD U01DK61734 (PI) May 2010-Apr 2014 NIH Clinical Research Network in Non-Alcoholic Steatohepatitis (NASH) 5 R01 DK (PI) Sept 2010-June 2015 NIH Technical Validation of MRI Biomarkers of Liver Fat R01DK (PI) Sept 2012-Aug 2017 NIH Intestinal bacterial metagenome in pediatric NAFLD R56DK (PI) Sept 2012-Aug 2014 NIH Development of MR Based Biomarker Panels for NAFLD-A NASH CRN Ancillary Study Mamata Sivagnanam, MD 1 K08 DK A2 (PI) Aug 2009-July 2014 $723,060 NIH (NIDDK) Intestinal Epithelial Function in Congenital Tufting Enteropathy (PI) Dec 2008-Dec 2011 $150,000 Children's Digestive Health Investigation of the Role of Epithelial Adhesion Molecule in the Intestinal Epithelium Acad Senate: Pilot Award (PI) July 2015-June 2016 Unfolded Protein Response in Mutant EpCAM Mice Rady Academic Enrichment Fund (PI) May 2014-Apr 2015 The Effect of Probiotics on Gut Microbiome and Adiposity 106 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 107

55 Genetics 108 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 109

56 INTRODUCTION The Division of Genetics is actively involved in clinical care, research, teaching and service. The Division sees more than 4,500 patients per year in a variety of clinics, primarily as outpatients at Rady Children s Hospital-San Diego, but also throughout Southern California, and in Mexico. The Division has an active inpatient consult service, and also sees more than 500 inpatients per year. Faculty members in the Division presently hold more than $5 million in grants and contracts, and have published over 70 original articles and chapters within the last two years. FACULTY Division faculty are actively engaged in teaching at all training levels, including graduate and medical students, residents and fellows, and community physicians. The Division has a number of internationally recognized leaders in their respective fields. Many Genetics Division faculty have held leadership positions in national organizations, including most notably the Presidencies of the American College of Medical Genetics (Dr. Jones) and the American Society of Gene Therapy (Dr. Friedmann). A number of Genetics Division faculty members have been recognized for outstanding contributions to their respective biomedical research fields: Dr. Friedmann was the winner of the 2015 Japan Prize for pioneering work in the gene therapy field; Dr. La Spada was designated a Gund-Harrington Scholar in 2015; and Dr. Rana was inducted as a Fellow into the American Association for the Advancement of Science in Patients come for our knowledge, expertise and innovation. From creating new programs which address specific patient populations to conducting research on obesity and its metabolic complications, we strive to be the best in this field. Over $9 million in research support DIVISION FAST FACTS The Division has a long-established tradition of excellence in specialized testing Albert R. La Spada, MD, PhD Professor Cellular & Molecular Medicine, Neurosciences, and Biological Sciences Associate Director, Institute for Genomic Medicine Division Chief Bruce Barshop, MD, PhD Professor of Clinical Pediatrics Director, Metabolic Disease Section Director, Biochemical Genetics & Metabolomics Laboratory Craig L. Bennett, PhD Assistant Adjunct Professor Lynne M. Bird, PhD Professor of Clinical Pediatrics Stephanie Cherqui, PhD Assistant Professor in Residence MAJOR PLANS AND GOALS Annette Feigenbaum, MD Staff Physician Theodore Friedmann, MD, PhD Professor Pamela Itkin-Ansari, PhD Associate Project Scientist of Pediatics Marilyn C. Jones, MD Professor of Clinical Pediatrics Clinical Service Chief Director, Cleft Palate & Craniofacial Treatment Programs Medical Director, Helen Bernardy Center for Medically-Fragile Children Alysson Muotri, PhD Associate Professor and Cellular & Molecular Medicine To fully incorporate genomic sequencing and omics-based technologies into the diagnostic work-up and management of patients with genetic disorders To develop the Genetics residency/fellowship into a leading academic training program To continue to perform research that is at the very forefront of defining the genetic basis for a variety of inherited and common disorders To utilize research advances to develop novel therapies for currently untreatable human diseases Robert K. Naviaux, MD, PhD Professor of Medicine Pediatrics, and Pathology in Residence Mark Nunes, MD Affilate Professor William L. Nyhan, MD, PhD Professor Tariq Rana, PhD Professor Vice Chair of Innovation in Therapeutics Mary Willis, MD Affiliate Associate Professor Kristen Wigby, MD, 1st year ( ) FELLOWS 110 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 111

57 The Division of Genetics provides a wide range of Clinical Genetics services to the greater San Diego community, including Pediatric Genetics, Biochemical Genetics, Cancer Genetics, and Reproductive Medicine care. Rady Children s Hospital-San Diego and UCSD Medical Center have a long established tradition of excellence in Biochemical Genetics. Hence, the Division maintains a Biochemical Genetics Laboratory that serves as a regional and international resource for basic research and clinical testing, including providing services to the California Newborn Screening Program. Genetics Division faculty oversee UCSD s Prenatal Diagnosis Upon Dr. La Spada s arrival in 2009, the Clinical Genetics fellowship training program was overhauled to broaden the scope of the trainee experience to expand opportunities for exposure to a broader range of inherited diseases, including cancer genetics at the NCI Moore s Cancer Center at UCSD, and a mix of adult and pediatric genetics at the Naval Medical Center San Diego and the Kaiser-Permanente Healthcare System. The Genetics fellowship program, whose Director is Dr. La Spada, is fully accredited to train Clinical Genetics, Biochemical Genetics, and Clinical Molecular Genetics fellows, and provides trainees with unparalleled opportunities to engage in cutting edge basic research, translational investigation, or clinical studies. This philosophy is supported by a training program curriculum that provides at least 80% protected time for research during 6 months of a trainee s second year, and encourages an optional third year to further immerse the trainee in a focused academic research PUBLICATIONS Dohil R, Cabrera BL, Gangoiti JA, Barshop BA, Rioux P. Pharmacokinetics of cysteamine bitartrate following intraduodenal delivery. Fundam Clin Pharmacol. 28:136, El-Gharbawy AH, Goldstein JL, Millington DS, Vaisnins AE, Schlune A, Barshop BA, Schulze A, Koeberl DD, Young SP. Elevation of guanidinoacetate in newborn dried blood spots and impact of early treatment in GAMT deficiency. Mol Genet Metab. 109:215, Gertsman I, Gangoiti JA, Barshop BA. Validation of a dual LC HRMS platform for clinical metabolic diagnosis in serum, bridging quantitative analysis and untargeted metabolomics. Metabolomics. 10:312, Gertsman I, Barshop BA, Panyard-Davis J, Gangoiti JA, Nyhan WL.. Metabolic Effects of Increasing doses of nitisinone in the treatment of alkaptonuria. JIMD Rep. 24:13, Gertsman I, Gangoiti JA, Nyhan WL, Barshop BA. Perturbations of tyrosine metabolism promote the indolepyruvate pathway via tryptophan in host and microbiome. Mol Genet Metab. 114:431, Khanna A, Gish R, Winter SC, Nyhan WL, Barshop BA. Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia. JIMD Rep. [Epub] July, UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report CLINICAL ACTIVITIES Center, evaluate patients at the UCSD Fetal Diagnosis Center, and provide consultations on various inpatient services at RCHSD, Sharp Mary Birch Hospital for Women, and Scripps system hospitals. Genetics Division faculty see patients in our outpatient Dysmorphology and Genetics clinics, direct the Prader-Willi syndrome clinic and the Down Syndrome Center, and provide services at clinics at the San Diego Regional Center for the Developmentally Disabled, Hospital de las Californias in Tijuana, and El Centro Regional Center for the Developmentally Disabled. TEACHING ACTIVITIES undertaking. Division faculty also take a leading role in training the next generation of physicians and physician-scientists in genetics, genomics, and medical genetics. Dr. La Spada serves as co- Director for the Genetics in Medicine Foundation block, which is required of all first year medical students, and is joined by most members of the Division who serve as lecturers or small group instructors. Division faculty also train Clinical Genetics fellows and residents in an annual Medical Genetics Didactics course which features a set of two lectures each week on basic genetics, cytogenetics, pediatric genetics, cancer genetics, molecular genetics, genomics, molecular diagnosis, prenatal genetics, and neurogenetics. RESEARCH ACTIVITIES LaBarge SA, Migdal CW, Buckner EH, Okuno H, Gertsman I, Stocks B, Barshop BA, Nalbandian SR, Philp A, McCurdy CE, Schenk S. p300 is not required for metabolic adaptation to endurance exercise training. FASEB J.[Epub] Dec, McCloskey D, Gangoiti JA, King ZA, Naviaux RK, Barshop BA, Palsson BO, Feist AM. A model-driven quantitative metabolomics analysis of aerobic and anaerobic metabolism in E. coli K-12 MG1655 that is biochemically and thermodynamically consistent. Biotechnol Bioeng. 111(4):803, Merritt JL 2nd, Vedal S, Abdenur JE, Au SM, Barshop BA, Feuchtbaum L, Harding CO, Hermerath C, Lorey F, Sesser DE, Thompson JD, Yu A. Infants suspected to have very-long chain acyl- CoA dehydrogenase deficiency from newborn screening. Mol Genet Metab. 111(4):484, 2014 Okamura DM, Bahrami NM, Ren S, Pasichnyk K, Williams JM, Gangoiti JA, Lopez-Guisa JM, Yamaguchi I, Barshop BA, Duffield JS, Eddy AA. Cysteamine modulates oxidative stress and blocks myofibroblast activity in CKD. J Am Soc Nephrol. 25(1):43, 2014 Schiffmann R, Ries M, Blankenship D, Nicholls K, Mehta A, Clarke JT, Steiner RD, Beck M, Barshop BA, Rhead W, West M, Martin R, Amato D, Nair N, Huertas P. Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa. Genet Med. 15(12):983, 2013 Sharma K, Karl B, Mathew AV, Gangoiti JA, Wassel CL, Saito R, Pu M, Sharma S, You YH, Wang L, Diamond-Stanic M, Lindenmeyer MT, Forsblom C, Wu W, Ix JH, Ideker T, Kopp JB, Nigam SK, Cohen CD, Groop PH, Barshop BA, Natarajan L, Nyhan WL, Naviaux RK. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol. 24(11):1901, Shepard PJ, Barshop BA, Baumgartner MR, Hansen J-B, Jepsen K, Smith EN, Frazer KA. Consanguinity and rare mutations outside of MCCC genes underlie non-specific phenotypes of MCC Deficiency. Genet Med. 17(8):660, 2015 Stockler-Ipsiroglu S, van Karnebeek C, Longo N, Korenke GC, Mercimek-Mahmutoglu S, Marquart I, Barshop B, Grolik C, Schlune A, Angle B, Araújo HC, Coskun T, Diogo L, Geraghty M, Haliloglu G, Konstantopoulou V, Leuzzi V, Levtova A, Mackenzie J, Maranda B, Mhanni AA, Mitchell G, Morris A, Newlove T, Renaud D, Scaglia F, Valayannopoulos V, van Spronsen FJ, Verbruggen KT, Yuskiv N, Nyhan W, Schulze A. Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring. Mol Genet Metab. 111(1):16, 2014 Li W, Zhu H, Zhao X, Brancho D, Liang Y, Zou Y, Bennett CL and Chow CW. Dysregulated Inflammatory Signaling upon CMT1C Mutation of Protein SIMPLE. Mol. Biol. Cell. 35(14):2464, Bennett CL & La Spada AR. Unwinding the role of senataxin in neurodegeneration. Discov. Med. 19(103):127, Zhu H, Guariglia S, Yu RYL, Li W, Brancho D, Salzer J, Bennett CL, and Chow CW. Mutation of SIMPLE in Charcot-Marie-Tooth 1C alters production of exosomes. Mol. Biol. Cell. 24(11):1619, Bennett CL, Chen YZ, Vignali M, Lo R, Mason A, Nabiha Huq Saifee, Field S and La Spada AR. Senataxin interactome analysis reveals evidence for senataxin self-association with ubiquitin- SUMO post-translational modification and uncovers novel peptide sequences that specifically interact with the ALS4 L389S mutant. PLoS One. 8(11) Baird F & Bennett CL. The molecular basis of microtubule defects and neurodegeneration. J Genet Syndr Gene Ther. 6(4): 203, Tatton-Brown K, Murray A, Hanks S, Douglas J, Armstrong R, Banka S, Bird LM, Clericuzio CL, Cormier-Daire V, Cushing T, Flinter F, Jacquemont ML, Joss S, Kinning E, Lynch SA, Magee A, McConnell V, Medeira A, Ozono K, Patton M, Rankin J, Shears D, Simon M, Splitt M, Strenger V, Stuuman K, Taylor C, Titheradge H, Van Maldergem L, Temple IK, Cole T, Seal S; Childhood Overgrowth Consortium, Rahman N. Weaver syndrome and EZH2 mutations: clarifying the clinical phenotype. Am J Med Genet A, 161(12):2972, Ross MK, Ellis LS, Bird LM, Hagood JS. Pulmonary interstitial glycogenosis in a patient ultimately diagnosed with Noonan syndrome. Pediatr Pulmonol.49(5):508, Overhoff J, Mikhaelian M, Bird LM, Schweitzer D, Haynes K, Schultz RA, Shaffer LG, Rosenfeld JA, Ellison JW. Refinement of the 8q22.1 microdeletion critical region associated with Nablus Mask- Like Facial Syndrome. Am J Med Genet A.164A(1): Bird LM. Angelman syndrome: Review of clinical and molecular aspects. Appl Clin Genet 7: Tan WH, Bird LM, Thibert RL, Williams CA. If not Angelman, what is it? A review of Angelman-like syndromes. Am J Med Genet A. 164A(4):975, Basehore MJ, Michaelson-Cohen R, Levy-Lahad E, Sismani C, Bird LM, Friez MJ, Walsh T, Abidi F, Holloway L, Skinner C, McGee S, Alexandrou A, Syrrou M, Patsalis PC, Raymond G, Wang T, Schwartz CE, King MC, Stevenson RE. Alpha-Thalassemia Intellectual Disability: Variable phenotypic expression among males with a recurrent nonsense mutation - c.109c>t (p.r37x). Clinical Genetics.87(5):461, Gripp KW, Robbins KM, Sobreira NL, Witmer PD, Bird LM, Avela K, Makitie O, Alves D, Hogue JS, Zackai EH, Doheny KF, Stabley DL, Sol-Church K. Truncating mutations in the last exon of NOTCH3 cause Lateral Meningocele Syndrome. Am J Med Genet A. 167A(2):271, Barea JJ, van Meel E, Kornfeld S, Bird LM. Tuberous Sclerosis, Polycystic Kidney Disease and Mucolipidosis III gamma caused by a microdeletion unmasking a recessive mutation. Am J Med Genet A. 167(11):2844, 2015 Koolen D, Pfundt R, Linda K, Beunders G, Veenstra-Knol H, Conta J, Fortuna AM, Gillessen-Kaesbach G, Dugan S, Halbach S, Abdul Rahman O, Winesett H, Chung LM, Dalton M, Dimova P, Mattina T, Prescott K, Zhang H, Saal H, Hehir-Kwa J, Ockeloen C, Jongmans M, van der Aa N, Failla P, Barone C, Avola E, Brooks A, Kant S, Gerkes E, Firth H, Ounap K, Bird L, Masser-Frye D, Friedman J, Sokunbi M, Dixit A, Splitt M, DDD Study, Kukolich M, McGaughran J, Coe B, Flórez J, Nadif Kasri N, Brunner H, Thompson E, Gecz J, Romano C, Eichler E, de Vries B, Willemsen M. The Koolen-de Vries syndrome: A phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant. 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EMBO Mol Med. 7(2): 158, Naphade S, Sharma J, Gaide Chevronnay HP, Shook MA, Yeagy BA, Rocca CJ, Ur SN, Lau AJ, Courtoy PJ, Cherqui S. Lysosomal crosscorrection by hematopoietic stem cell-derived macrophages via tunneling nanotubes. Stem Cells. 33(1):301, 2015* Rocca CJ, Ur SN, Harrison F, Cherqui S. (2014) raav9 combined with renal vein injection is optimal for kidney-targeted gene delivery: conclusion of a comparative study. Gene Ther. 21(6):618, Burton B, Grant M, Feigenbaum A, Singh R, Hendren R, Siriwardena K, Phillips J 3rd, Sanchez-Valle A, Waisbren S, Gillis J, Prasad S, Merilainen M, Lang W, Zhang C, Yu S, Stahl S. A randomized, placebo-controlled, double-blind study of sapropterin to treat ADHD symptoms and executive function impairment in children and adults with sapropterin-responsive phenylketonuria. Mol Genet Metab. 114(3):415, Cameron JM, MacKay N, Feigenbaum A, Tarnopolsky M, Blaser S, Robinson BH, Schulze A. Exome sequencing identifies complex I NDUFV2 mutations as a novel cause of Leigh syndrome. Eur J Paediatr Neurol. 19(5): Clinical outcomes of neonatal onset proximal versus distal urea cycle disorders do not differ. Ah Mew N, Krivitzky L, McCarter R, Batshaw M, Tuchman M, and the Urea Cycle Disorders Consortium of the Rare Diseases Clinical Research Network (22 collaborators, including Feigenbaum A). J Pediatr.; 162(2):324, Feigenbaum A, Mu ller C, Yale C, Kleinheinz J, Jezewski P, Kehl HG, MacDougall M, Rutsch F, Hennekam RC. Singleton-Merten syndrome: an autosomal dominant disorder with variable expression. Am J Med Genet A.;161A(2):360, Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 113

58 Kevelam SH, Bugiani M, Salomons GS, Feigenbaum A, Blaser S, Prasad C, Häberle J, Baric I, Bakker IM, Postma NL, Kanhai WA, Wolf NI, Abbink TE, Waisfisz Q, Heutink P, van der Knaap MS. Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy. Brain.136(Pt 5):1534, 2013 Khangura SD, Karaceper MD, Trakadis Y, Mitchell JJ, Chakraborty P, Tingley K, Coyle D, Grosse SD, Kronick JB, Laberge AM, Little J, Prasad C, Sikora L, Siriwardena K, Sparkes R, Speechley KN, Stockler S, Wilson BJ, Wilson K, Zayed R, Potter BK and the Canadian Inherited Metabolic Diseases Research Network (31 collaborators, including Feigenbaum A). Scoping review of patientand family-oriented outcomes and measures for chronic pediatric disease. BMC Pediatr. 15:7, 2015 Lamoureux MF, Tingley K, Kronick JB, Potter BK, Chan AK, Coyle D, Dodds L, Dyack S, Feigenbaum A, Geraghty M, Gillis J, Rockman-Greenberg C, Khan A, Little J, MacKenzie J, Maranda B, Mhanni A, Mitchell JJ, Mitchell G, Laberge AM, Potter M, Prasad C, Siriwardena K, Speechley KN, Stockler S, Trakadis Y, Turner L, Van Karnebeek C, Wilson K, Chakraborty P, and the Canadian Inherited Metabolic Diseases Research Network. Metabolic Clinic Atlas: Organization of Care for Children with Inherited Metabolic Disease in Canada. JIMD Rep. 21:15, 2015 Lee B, Diaz GA, Rhead W, Lichter-Konecki U, Feigenbaum A, Berry SA, Le Mons C, Bartley JA, Longo N, Nagamani SC, Berquist W, Gallagher R, Bartholomew D, Harding CO, Korson MS, McCandless SE, Smith W, Cederbaum S, Wong D, Merritt JL 2nd, Schulze A, Vockley J, Kronn D, Zori R, Summar M, Milikien DA, Marino M, Coakley DF, Mokhtarani M; UCD Consortium, Scharschmidt BF. Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder. Genet Med. 17(7):561, 2015 Longo N, Siriwardena K, Feigenbaum A, Dimmock D, Burton BK, Stockler S, Waisbren S, Lang W, Jurecki E, Zhang C, Prasad S. Longterm developmental progression in infants and young children taking sapropterin for phenylketonuria: a two-year analysis of safety and efficacy. Genet Med. 17(5):365, 2015 Mokhtarani M, Diaz GA, Rhead W, Berry SA, Lichter-Konecki U, Feigenbaum A, Schulze A, Longo N, Bartley J, Berquist W, Gallagher R, Smith W, McCandless SE, Harding C, Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Dickinson K, Moors T, Norris C, Coakley D, Milikien DA, Nagamani SC, Lemons C, Lee B, Scharschmidt BF. Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio. Mol Genet Metab. 2013;110(4): PMID: Nagamani SC, Diaz GA, Rhead W, Berry SA, Le Mons C, Lichter- Konecki U, Bartley J, Feigenbaum A, Schulze A, Longo N, Berquist W, Gallagher R, Bartholomew D, Harding CO, Korson MS, McCandless SE, Smith W, Vockley J, Kronn D, Zori R, Cederbaum S, Merritt JL 2nd, Wong D, Coakley DF, Scharschmidt BF, Dickinson K, Marino M, Lee BH, Mokhtarani M. Self-reported treatmentassociated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials. Mol Genet Metab. 116(1-2):29-34, 2015 Nasr E, Mamak E, Feigenbaum A, Donner EJ, Mercimek- Mahmutoglu S. Long-term treatment outcome of two patients with pyridoxine-dependent epilepsy caused by ALDH7A1 mutations: normal neurocognitive outcome. J Child Neurol. 30(5):648, Potter BK, Chakraborty P, Kronick JB, Wilson K, Coyle D, Feigenbaum A, Geraghty MT, Karaceper MD, Little J, Mhanni A, Mitchell JJ, Siriwardena K, Wilson BJ, Syrowatka A, and the Canadian Inherited Metabolic Diseases Research Network. Achieving the "triple aim" for inborn errors of metabolism: a review of challenges to outcomes research and presentation of a new practice-based evidence framework. Genet Med. 15(6):415, Rehm HL, Berg JS, Brooks LD, Bustamante CD, Evans JP, Landrum MJ, Ledbetter DH, Maglott DR, Martin CL, Nussbaum RL, Plon SE, Ramos EM, Sherry ST, Watson MS, and ClinGen (212 collaborators, including Feigenbaum A). ClinGen--the Clinical Genome Resource. N Engl J Med. 372(23):2235, Roscher A, Patel J, Hewson S, Nagy L, Feigenbaum A, Kronick J, Raiman J, Schulze A, Siriwardena K, Mercimek-Mahmutoglu S. The natural history of glycogen storage disease types VI and IX: Longterm outcome from the largest metabolic center in Canada. Mol Genet Metab. 113(3):171, van Berge L, Hamilton EM, Linnankivi T, Uziel G, Steenweg ME, Isohanni P, Wolf NI, Krägeloh-Mann I, Brautaset NJ, Andrews PI, de Jong BA, al Ghamdi M, van Wieringen WN, Tannous BA, Hulleman E, Wu rdinger T, van Berkel CG, Polder E, Abbink TE, Struys EA, Scheper GC, van der Knaap MS, and the LBSL Research Group (including Feigenbaum A). Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy. Brain. 137(Pt 4):1019,2014 Rutsch F, MacDougall M, Lu C, Buers I, Mamaeva O, Nitschke Y, Rice GI, Erlandsen H, Kehl HG, Thiele H, Nu rnberg P, Höhne W, Crow YJ, Feigenbaum A, Hennekam RC. A specific IFIH1 gain-offunction mutation causes Singleton-Merten syndrome. Am J Hum Genet 96(2):275, Kang TH, Park Y, Bader JS, Friedmann T. The housekeeping gene hypoxanthine guanine phosphoribosyltransferase (HPRT) regulates multiple developmental and metabolic pathways of murine embryonic stem cell neuronal differentiation. PLoS One. 8(10):e doi: Friedmann T, Jonlin EC, King NM, Torbett BE, Wivel NA, Kaneda Y, Sadelain M. ASGCT and JSGT Joint Position Statement on Human Genomic Editing. Mol Ther.; 23(8):1282, Kang TH, Friedmann T. Alzheimer's disease shares gene expression aberrations with purinergic dysregulation of HPRT deficiency (Lesch-Nyhan disease). Neurosci Lett. 590: *Kim S, Lahmy R, Riha C, Yang C, Jakubison BL, van Niekerk J, Staub C, Wu Y, Gates K, Dong DS, Konieczny SF, Itkin-Ansari P. The bhlh transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenicity. Pancreas. 44(5):718, Hassler, J. R., Scheuner, D. L., Wang, S., Han, J., Kodali, V. K., Li, P., Nguyen, J., George, J. S., Davis, C., Wu, S. 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The utilization of circulating Cell-free fetal DNA testing and decrease in invasive diagnostic procedures: an institutional experience. J Perinatol. 1-4 (10):750, Sahoo T, Wang JC, El Naggar MM, Sanchez-Lara P, Ross LP, Mahon LW, Hafezi K, Deming A, Hinman L, Bruno Y, Bartley JA, Liehr T, Anguiano A, Jones MC. Concurrent triplication and uniparental isodisomy: Evidence for microhomology-mediated break-induced replication model for genomic rearrangements. Eur J Hum Genet. 23:61, Shah R, Steinhaus-French K, Osann K, Bocian M, Jones MC, Korty L. Impact of Cell-Free Fetal DNA Screening on Patients Choice of Invasive Procedures After a Positive California Prenatal Screen Result. J Clin Med. 3:849, Wang JC, Ross L, Mahon LW, Owen R, Hemmat M, Wang BT, El Naggar M, Kopita KA, Randolph LM, Chase JM, Matas Aguilera MJ, López Siles J, Church JA, Hauser N, Shen JJ, Jones MC, Wierenga KJ, Jiang Z, Haddadin M, Boyar FZ, Anguiano A, Strom CM, Sahoo T. Regions of Homozygosity Identified by Oligonucleotide SNP Array: Evaluating the Incidence and Clinical Utility. Eur J Hum Genet. 19: 23(5):663, Malik B, Nirmalanthan N, Gray A, La Spada AR, Hanna MG & Greensmith L. Co-induction of the heat shock response ameliorates disease in a mouse model of spinal bulbar muscular atrophy: implications for therapy. Brain. 136: 926, Fratta P, Malik B, Gray A, La Spada AR, Hanna MG, Fisher EM & Greensmith L. FUS is not dysregulated by the SBMA androgen receptor polyglutamine repeat expansion. Neurobiology of Aging. 34: 1516.e17, Furrer SA, Waldherr SM, Mohanachandan MS, Baughn TD, Nguyen KT, Sopher BL, Damian VA, Garden GA & La Spada AR. Reduction of mutant ataxin-7 expression restores motor function and prevents cerebellar synaptic reorganization in a conditional mouse model of SCA7. Human Molecular Genetics. 22: 890, Nakamura Y, Fujita K, Oka T, Ito H, Tagawa K, Sasabe T, Katsuta A, Tamura T, Motoki K, Sone M, Toshida C, Katsuno M, Eishi Y, Murata M, Taylor JP, Wanker EE, Kono K, Tashiro S, Sobue G, La Spada AR & Okazawa H. A functional deficiency of TERA/VCP/ p97 in DNA double strand break repair is responsible for multiple polyglutamine diseases. Nature Communications. 4: 1816, Mason AG, Tome S, Smard J, Libby RT, Bammler TK, Beyer RP, Morton AJ, Pearson CE & La Spada AR. Expression levels of DNA replication and repair genes predict regional somatic repeat instability in the brain but are not altered by polyglutamine disease protein expression or age. Human Molecular Genetics. 23: 1606, *Cortes CJ, Ling S-C, Guo LT, Hung G, Tsunemi T, Ly L, Lopez E, Sopher BL, Bennett CF, Shelton GD, Cleveland DW & La Spada AR. Muscle expression of mutant androgen receptor accounts for systemic and motor neuron disease phenotypes in Spinal & Bulbar Muscular Atrophy. Neuron. 82: 295, Lieberman AP, Yu Z, Murray S, Peralta R, Low A, Guo S, Cortes CJ, Bennett FC, Monia B, La Spada AR & Hung G. Peripheral androgen receptor gene suppression rescues disease in mouse models of Spinal and Bulbar Muscular Atrophy. Cell Reports. 7: 1, McCormick MA, Mason AG, Guyenet SJ, Dang W, Garza RM, Ting MK, Moller RM, Berger SL, Kaeberlein M, Pillus L, La Spada AR* & Kennedy BK*. The SAGA histone deubiquitinase modules controls yeast replicative lifespan via interaction with Sir2. Cell Reports. 8: 477, *Cortes CJ, Miranda HC, Frankowski H, Batlevi Y, Young JE, Le A, Ivanov N, Sopher BL, Carromeu C, Muotri AR, Garden GA & La Spada AR. Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA. Nature Neuroscience. 17: 1180, *Dubinsky AN, Dastidar SG, Zahra R, Hsu CL, Djakovic S, Esau CC, Spencer B, Ashe TD, Fischer KM, MacKenna DA, Sopher BL, Masliah E, Gaasterland T, Chau NB, Morrison BE & La Spada AR. 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59 G.G. Altered ipsc-derived neurons sodium channel propoerties in subjects with Monge s disease. Neuroscience. 14: 1088, *Griesi-Oliveira, K., Acab, A., Gupta, A., Sunaa, D. Chailangkarn, T., Nicol, X., Nunez, Y., Walker, M., Murdoch, Jo., Sanders, S., Fernandez, T., Ji, W., Lifton, R., Vadasz, E., Dietrich, A., Pradhan, D., Song, H., Ming, G., Guoe, X., Haddad, G., Marchetto, M., Sptzer, N., Passos-Bueno, M., State, M. & Muotri, A.R. Modeling nonsyndromic autism and the impact of TRPC6 disruption in human neurons. Mol. Psychiatry 1: 1, Stein, J.L., de la Torre-Ubieta, L., Tian, Y., Parikshak, N.N., Hernandez, I.A., Marchetto, M.C., Baker, D.K., Lu, D., Hinman, C.R., Lowe, J.K., Wexler, E.M., Muotri, A.R., Gage, F.H., Kosik, K.S. & Geschwind, D.H. A quantitative framework to evaluate modeling of cortical development by neural stem cells. Neuron. 83: 69, Herai, R.R., Stefanacci, L., Hrvoj-Mihic, B., Chailangkarn, T., Hanson, K., Semendeferi, K. & Muotri, A.R. Micro RNA detection in long-term fixed tissue of cortical glutamatergic pyramidal neurons after targeted laser-capture neuroanatomical microdissection. Journal of neuroscience methods. 235C: 76, Hrvoj-Mihic, B., Bienvenu, T., Stefanacci, L., Muotri, A.R. & Semendeferi, K. Evolution, development, and plasticity of the human brain: from molecules to bones. Front. Hum. Neurosci. 7: 707, *Marchetto, M.C.N., Narvaiza, I., Denli, A.M., Benner, C., Lazzarini, T.A., Nathanson, J.L., Paquola, A.C.M., Desai, K.N., Herai, R.H., Weitzman, M.D., Yeo, G.W., Muotri, A.R. & Gage, F.H. Differential LINE-1 regulation in pluripotent stem cells of humans and other great apes. Nature. 503: 525, Hrvoj-Mihic, B., Marchetto, M. C., Gage, F. H., Semendeferi, K., Muotri, A.R. Novel tools, classic techniques: evolutionary studies using primate pluripotent stem cells. Biol Psychiatry. 13: 736, Yoshioka, N., Gros, E., Li, H.R., Kumar, S., Deacon, D.C., Maron, C. Muotri, A.R., Chi, N.C., Fu, X.D., Yu, B.D., Dowdy, S.F. Efficient generation of human ipscs by a synthetic self-replicative RNA. Cell Stem Cell. 13:246, Tang, X., Zhou, L., Wagner, A.M., Marchetto. M.C.N., Muotri, A. R., Gage, F.H., & Chen, G. Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells. Stem Cell Research. 2:743, Muotri, A. R. Voices: Stem Cells in Translation. Brain in a dish. Cell. 153, (2013). Lovatel, G. A., Elsner, V. R., Bertoldi, K., Vanzella, C., Moyses, F. D., Vizuete, A., Spindler, C., Cechinel, L. R., Netto, C. A., Muotri, A. R. & Siqueira, I. R. Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus. Neurobiol Learn Mem. 13: 20, Beltrao-Braga, P. C., Pignatari, G. C., Russo, F. B. Fernandes, I. R. & Muotri, A. R. In-a-dish: induced pluripotent stem cells as a novel model for human diseases. Cytometry A. 83: 11, Levy DJ, Pretorius DH, Rothman A, Gonzales M, Rao C, Nunes ME, Bendelstein J, Mehalek K, Thomas A, Nehlsen C, Ehr J, Burchette RJ, Sklansky MS.Improved prenatal detection of congenital heart disease in an integrated health care system. Pediatr Cardiol. 34(3):670, Naviaux JC, Schuchbauer MA, Li K, Wang L, Risbrough VB, Powell SB et al. Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy. Translational psychiatry. 4: e400, doi: /tp Naviaux JC, Wang L, Li K, Bright AT, Alaynick WA, Williams KR et al. Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model. Molecular autism. 6: 1, Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, Hegde M, Visser JE, Schretlen DJ, Nyhan WL, Puig JG, O'Neill PJ, Jinnah HA; Lesch-Nyhan Disease International Study Group. Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. Brain. 137(Pt 5):1282, Dolcetta D, Parmigiani P, Salmaso L, Bernardelle R, Cesari U, Andrighetto G, Baschirotto G, Nyhan WL, Hladnik U. Quantitative evaluation of the clinical effects of S-adenosylmethionine on mood and behavior in Lesch-Nyhan patients. Nucleosides Nucleotides Nucleic Acids. 32(4):174, Stockler-Ipsiroglu S, van Karnebeek C, Longo N, Korenke GC, Mercimek-Mahmutoglu S, Marquart I, Barshop B, Grolik C, Schlune A, Angle B, Araújo HC, Coskun T, Diogo L, Geraghty M, Haliloglu G, Konstantopoulou V, Leuzzi V, Levtova A, Mackenzie J, Maranda B, Mhanni AA, Mitchell G, Morris A, Newlove T, Renaud D, Scaglia F, Valayannopoulos V, van Spronsen FJ, Verbruggen KT, Yuskiv N, Nyhan W, Schulze A. Guanidinoacetate methyltransferase (GAMT) deficiency: outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring. Mol Genet Metab 111(1):16, 2014 Gertsman I, Barshop BA, Panyard-Davis J, Gangoiti JA, Nyhan WL. Metabolic effects of increasing doses of nitisinone in the treatment of alkaptonuria. JIMD Rep. 2015;24:13-20 Gertsman I, Gangoiti JA, Nyhan WL, Barshop BA. Perturbations of tyrosine metabolism promote the indolepyruvate pathway via tryptophan in host and microbiome. Mol Genet Metab. 114:431, Nguyen KV, Nyhan WL. Lesch-Nyhan syndrome in a family with a deletion followed by an insertion within the HPRT1 gene. Nucleosides, Nucleotides, and Nucleic Acids. 34:442, Nguyen KV, Nyhan WL. Mutation in the human HPRT1 gene and the Lesch-Nyhan syndrome. Nucleosides, Nucleotides, Nucleic Acids. 34(6):442, Khanna A, Gish R, Winter SC, Nyhan WL, Barshop BA. Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia. JIMD Rep. [Epub] July, 2015 Baigude H, Su J, McCarroll J, Rana TM. In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (inops). ACS Med Chem Lett. 4(8):720, Baigude H, Rana TM. Strategies to antagonize mirna functions in vitro and in vivo. Nanomedicine (Lond). 9(16):2545, 2014 Han J, Cai J, Borjihan W, Ganbold T, Rana TM, Baigude H. Preparation of novel curdlan nanoparticles for intracellular sirna delivery. Carbohydr Polym. 117:324, 2015 Henzler CM, Li Z, Dang J, Arcila ML, Zhou H, Liu J, Chang KY, Bassett DS, Rana TM, Kosik KS. Staged mirna re-regulation patterns during reprogramming. Genome Biol. 14(12):R149, *Li Z, Chao TC, Chang KY, Lin N, Patil VS, Shimizu C, Head SR, Burns JC, Rana TM. The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnrnpl. Proc Natl Acad Sci U S A. 111(3):1002, Li Z, Dang J, Chang KY, Rana TM. MicroRNA-mediated regulation of extracellular matrix formation modulates somatic cell reprogramming. RNA Dec;20(12): Li Z, Rana TM. Decoding the noncoding: prospective of lncrnamediated innate immune regulation. RNA Biol.11(8):979, *Li Z, Rana TM. Therapeutic targeting of micrornas: current status and future challenges. Nat Rev Drug Discov. 13(8):622, *Lin N, Chang KY, Li Z, Gates K, Rana ZA, Dang J, Zhang D, Han T, Yang CS, Cunningham TJ, Head SR, Duester G, Dong PD, Rana TM. An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment. Mol Cell. 53(6):1005, 2014 Lin N, Dang J, Rana TM. Haunting the HOXA Locus: Two Faces of lncrna Regulation. Cell Stem Cell. 16(5):449, McCarroll JA, Dwarte T, Baigude H, Dang J, Yang L, Erlich RB, Kimpton K, Teo J, Sagnella SM, Akerfeldt MC, Liu J, Phillips PA, Rana TM, Kavallaris M. Therapeutic targeting of polo-like kinase 1 using RNA-interfering nanoparticles (inops) for the treatment of non-small cell lung cancer. Oncotarget. 6(14):12020, Nalam MN, Ali A, Reddy GS, Cao H, Anjum SG, Altman MD, Yilmaz NK, Tidor B, Rana TM, Schiffer CA. Substrate envelopedesigned potent HIV-1 protease inhibitors to avoid drug resistance. Chem Biol. 20(9):1116, Patil VS, Zhou R, Rana TM. Gene regulation by non-coding RNAs. Crit Rev Biochem Mol Biol. 49(1):16, *Sakurai K, Talukdar I, Patil VS, Dang J, Li Z, Chang KY, Lu CC, Delorme-Walker V, Dermardirossian C, Anderson K, Hanein D, Yang CS, Wu D, Liu Y, Rana TM. Kinome-wide functional analysis highlights the role of cytoskeletal remodeling in somatic cell reprogramming. Cell Stem Cell. 14(4):523, Shen Y, Altman MD, Ali A, Nalam MN, Cao H, Rana TM, Schiffer CA, Tidor B. Testing the substrate-envelope hypothesis with designed pairs of compounds. ACS Chem Biol. 8(11):2433, Silver NW, King BM, Nalam MN, Cao H, Ali A, Kiran Kumar Reddy GS, Rana TM, Schiffer CA, Tidor B. Efficient Computation of Small-Molecule Configurational Binding Entropy and Free Energy Changes by Ensemble Enumeration. J Chem Theory Comput. 2013; 9(11):5098, Xiong XP, Kurthkoti K, Chang KY, Lichinchi G, De N, Schneemann A, MacRae IJ, Rana TM, Perrimon N, Zhou R. Core small nuclear ribonucleoprotein particle splicing factor SmD1 modulates RNA interference in Drosophila. Proc Natl Acad Sci U S A. 110(41):16520, *Yang CS, Chang KY, Rana TM. Genome-wide functional analysis reveals factors needed at the transition steps of induced reprogramming. Cell Rep. 8(2):327, Yang CS, Rana TM. Learning the molecular mechanisms of the reprogramming factors: let's start from micrornas. Mol Biosyst. 9(1):10, Zhou R, Rana TM. RNA-based mechanisms regulating host-virus interactions. Immunol Rev. 253(1):97, Miller, KE, Willis MJ, McClatchey, SK. A case of familial exudative vitreoretinopathy identified after genetic testing. J AAPOS. 19(2):178, Arboleda VA, Lee H, Dorrani N, Zadeh N, Willis M, Macmurdo CF, Manning MA, Kwan A, Hudgins L, Barthelemy F, Miceli MC, Quintero-Rivera F, Kantarci S, Strom SP, Deignan JL; UCLA Clinical Genomics Center, Grody WW, Vilain E, Nelson SF. De novo mutations in KAT6A, a lysine acetyl0transferase gene, cause a syndrome including microcephaly and global developmental delay. Am J Hum Genet. 96(3):498, BOOK CHAPTERS Bird LM, Jones KL. Systemic Vasculature. In: Human Malformations and Related Anomalies. Stevenson RE, Hall JG, Everman D, Solomon B (eds.). Oxford University Press, New York, 2015 Cherqui S, Kalatzis V, Cherqui S, Antignac C. Cystinosis. In Genetic Diseases of the kidney, Second Edition. Elsevier Jones MC. Facial clefting. In Hudgins L, Toriello H, Enns G, Hoyme HE (eds). In Signs and Symptoms of Genetic Disease. Oxford, La Spada AR. Kennedy s Disease. In: Aminoff MJ & Daroff RB (eds.) Encyclopedia of the Neurological Sciences. 2nd edition, Vol. 4, pp Oxford Academic Press, van Es MA & La Spada AR. Trinucleotide Repeat Disorders. In: Aminoff MJ & Daroff RB (eds.) Encyclopedia of the Neurological Sciences. 2nd edition, Vol. 4, pp Oxford Academic Press, Rangasamy, S.; Narayanan, M.; Schrauwen, I.; Muotri, A.R. & Narayanan, V. Cellular and animal models of neurological disease. In Swaiman's Pediatric Neurology: Principles and Practice, 6th edition; Editors: Ken Swaiman, Stephen Ashwal, Donna Ferriero, Nina Schor, Rick Finkel, Andrea Gropman, Phil Pearl, Michael Shevell (Eds). Chapter 16. Elsevier Ed Muotri, A.R. The ipsc technology to study neurodevelopmental disorders. In: Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability. Carlo Sala & Chiara Verpelli (Eds). Chapter 18. Elsevier Ed Muotri, A.R. Modeling autism spectrum disorders using human neurons. In Programmed Cells from Basic Neuroscience to Therapy. Gage & Christen (Eds.). Chapter 4. IPSEN Fondation. Ed Marchetto, M.C.N., Muotri, A.R. & Gage, F.H. Proposing a model for studying primate development using induced pluripotent stem cells. In Programmed Cells from Basic Neuroscience to Therapy. Gage & Christen (Eds.). Chapter 4. IPSEN Fondation. Ed Beltrao-Braga, P.C. B., Freitas, B. C. G. & Muotri, A. R. The rise of a new model for autism spectrum disorders. In Special School on Autism Spectrum Disorders. Goyos/Higbee/Miguel (eds.). Chapter 2. FAPESP Ed Muotri, A. R. Células-tronco, simples assim. Atheneu Ed. Entire book on stem cell biology for lay people. Preface by Dr. Larry Goldstein (UCSD) and cartoons by Ziraldo. (Portuguese. Spanish version currently under consideration) Nyhan WL. Lesch-Nyhan syndrome. In: Aminoff MJ, Daroff RB (eds.) Encyclopedia of the Neurological Sciences, 2nd edition, Vol 2, pp Oxford Academic Press Nyhan WL, O Neill JP, Jinnah HA, et al. Lesch-Nyhan syndrome [Updated May 2014] in: Pagon RA, Adam MP, Ardinger HH, et al., Editors. GeneReviews, Seattle, WA: University of Washington, Seattle; Nyhan WL, Haas RA. Inborn errors of amino acid metabolism. In: Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth Edition). Edited by: Rosenberg R and Pascual J. Academic Press 2015, pp Nyhan WL. Disorders of purine metabolism. In: Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth Edition)., pp Edited by: Rosenberg R and Pascual J. Academic Press 2015 AWARDS Bruce A. Barshop, MD, PhD Communicating Editor, Journal of Inherited Metabolic Disease Informatics Chair, Secretary, Society for Inherited Metabolic Disorders Guidelines Committee, California Newborn Screening Program Web Site Oversight Committee, American College of Medical Genetics Benard L. Maas Chair in Inherited Metabolic Disease, UCSD, 2007-present 116 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 117

60 Lynne M. Bird, MD Secretary-Treasurer of the Academy of Clinician Scholars, 2013 Theodore Friedmann, MD, PhD Advisory Council, American Society of Gene and Cell Therapy Chairman, Ethics Committee, American Society of Gene and Cell Therapy Board of Directors, Agouron Institute, Pasadena, California Chairman, Gene Doping Expert Committee, World Anti-Doping Agency, Montreal, Canada The Japan Prize Marilyn C. Jones, MD Member, Committee on Data Standards, American Cleft Palate-Craniofacial Assn. Co-chair, Preconference Symposium, American Cleft Palate-Craniofacial Assn., Chair, Commission on Approval of Teams present. Member, Committee on Genetics, American Academy of Pediatrics present. Member, Basil O Connor Review Committee, March of Dimes present. Albert R. La Spada, MD, PhD Telethon Scientific Review Committee (Government of Italy): present. Medical Review Advisory Board. National Ataxia Foundation present. Inducted into the American Association of Physicians (AAP): 2013 Gund-Harrington Scholar Award (Harrington Discovery Institute): 2015 Alysson Muotri, PhD Winner of Pride Autism Brazil : Robert K. Naviaux, MD, PhD Appointed as international advisor to the Association Française contre les Myopathies, Plateforme Maladies Rares (AFM The French Muscular Dystrophy and Rare Disease Council), Paris, France William L. Nyhan, MD, PhD Member Scientific Advisory Board, United Mitochondrial Disease Foundation Presenter, Lesch-Nyhan Disease, Menarini Ricerche, Florence, Italy, September 2013 Tariq Rana, PhD Avant-Garde Award from the NIH: Elected fellow of American Association for the Advancement of Science: GRANTS AND SUPPORT Bruce Barshop, MD, PhD Genetic factors involving expression of 3-methylcrotonyl-CoA carboxylase deficiency (Barshop, PI) NIH R03 HD $ $154,542 Aug to Jul Metabolomic Studies of Lysosomal Storage Disorders: Correlation of Outcomes in Gaucher Disease and Pompe Disease (Barshop, PI) Genzyme $ $104,750 Jan to Jan Novel Paradigms in Diabetic Complications (Barshop, co-i) NIH DP3 DK $ $5,950,661 Sept to Aug San Diego Clinical and Translational Research Institute (Barshop, co-i) NIH UL $ $4,910,558 Apr to Mar Improvement of Intracellular Cystine Determination (Barshop, PI) Cystinosis Research Foundation $ 59,286 Sept to Aug Aug to Jul Craig Bennett, PhD ALS4 mice show TDP-43 protein mislocalization in motor neurons characteristic of sporadic ALS patients (Bennett, PI) NHMRC (Australia) APP ) $270, Neuronal RNA processing defects in ALS4 caused by SETX mutation (Bennett, PI) NIH/NIGMS R01-GM $1,000, Lynne Bird, MD Trial of Levodopa for Angelman syndrome (Bird, PI) Angelman Syndrome Foundation $72,565 Mar Feb Rare Diseases Clinical Research Network (Bird, co-i) Grant #9U54HD $491,775 Aug July 2014 Phase II Trial of Levodopa in Angelman syndrome (Bird, co-i) FDA $298,066 August 2010 July 2014 Stephanie Cherqui, Ph.D Lentiviral-transduced hematopoietic stem cell transplantation for cystinosis (Cherqui, PI) NIH/NIDDK R01-DK $1,204,445 Jan Dec Toxicology studies for gene-modified stem cell transplantation for cystinosis (Cherqui, PI) NIH/NIDDK R01-DK $1,445,615 Aug May 2015 Pharmacology/Toxicology studies for gene-modified stem cell transplantation for cystinosis (Cherqui, PI) Cystinosis Research Foundation $539,400 Aug July 2016 Mechanism of bone marrow stem cell-mediated therapy in the mouse model of cystinosis (Cherqui, PI) Cystinosis Research Foundation $426,250 Aug July 2015 Kidney-targeted gene delivery for cystinosis (Cherqui, PI) NIH/NIDDK R21-DK $275,000 Sept Aug Theodore Friedmann, MD, PhD Lesch-Nyhan Disease, a model for complex genetic, proteomic and metabolic pathway (Friedmann, PI) NIH/NIDDK R24-DK $4,737,000 Aug Aug 2013 Understanding how abnormal purine metabolism leads to neurological abnormalities in LND cells (Friedmann, PI) Lesch-Nyhan Syndrome Children s Research Foundation $65,045 April 2010 to Present Pamela Itkin-Ansari, PhD Individual Biomedical Research Award (Itkin-Ansari, PI) The Hartwell Foundation $300,000 May 2011 to April 2014 Albert La Spada, MD, PhD Models of SBMA motor neuron degeneration (La Spada, PI) NIH/NINDS R01 NS $1,250,000 Sept 2010 to Aug 2015 Modeling motor neuron degeneration in SBMA (La Spada, PI) Muscular Dystrophy Association. $300,000 Aug 2013 to July 2016 SCA7 neurodegeneration: Molecular epigenetic basis & therapy (La Spada, PI) NIH/NEI R01 EY $1,750,000 Mar 2012 to Feb 2017 Role of Nna1 in retinal and cerebellar neurodegeneration (La Spada, PI) NIH/NEI R01 EY $1,000,00 Sep 2011 to Aug 2015 Antisense oligonucleotide knock-down of ataxin-7 in a SCA7 mouse model (La Spada, PI) NIH/NINDS R21 NS $275,000 Sep 2012 to Aug 2014 Molecular genetic regulation of autophagy in health & neurodegenerative disease (La Spada, PI) NIH/NIA R01 AG $1,525,000 Sep 2015 to May 2020 Development of an oligonucleotide therapy for knock-down of a toxic disease protein in spinocerebellar ataxia type 7 retinal degeneration (La Spada, PI) Harrington Discovery Institute FFB $900,000 July 2015 to June 2018 Alysson Muotri, PhD Modeling autism with human pluripotent cells (Muotri, PI) - Director s New Innovator Award NIH/DP2 OD $1,500,000 Sept to Sept Modeling Autism Spectrum Disorders using human neurons (Muotri, PI) Emerald Foundation, Inc. Young Investigator Award $150,000 Dec to Dec Developing a drug-screening system for ASD using human neurons (Muotri, PI) CIRM $1,491,000 Jan to Mar Modeling familial ALS8 with human induced pluripotent stem cells (Muotri, PI) Muscular Dystrophy Association. $360,000 Jan to Jan The Impact of L1 retrotransposition in the nervous system (Muotri, PI) NIH/NIMH R01 MH $1,000,000 July 2011 to June 2016 Modeling anorexia nervosa with human pluripotent stem cells (Muotri, PI) NIH/NIM R01 MH $225,000 Apr to Mar Contribution of human astrocytes to Rett syndrome (Muotri, PI) IRSF $100,000 Jan to Jan A chimeric brain model to study human neurological diseases (Muotri, PI) NIH/NIMH R21 MH $275,000 Sep 2015 to Jun 2017 Robert K. Naviaux, MD, PhD Novel Paradigms in Diabetic Complications (Naviaux, PI) NIH/NIDDK DP3 DK $3,800,000 Nov to Oct Therapeutic Approaches to Mitochondrial Disease (Naviaux, PI) The William Wright Foundation $100,000 Sept to Aug Mechanisms of Mitochondrial Disease (Naviaux, PI) UCSD Foundation Christini Fund $75,000 / year Oct to Present Mechanisms of Mitochondrial Disease (Naviaux, PI) UCSD Mitochondrial Research Fund The 5k Mito Walk And Roll $40,000 Feb to Jan Purinergic Signaling in Autism (Naviaux, PI) Jane Botsford Johnson Foundation $424,000 April 2013 to Mar Mark E. Nunes, MD Use of Electronic Medical Records (EMR) for Clinical Genetic Diagnoses (Nunes, PI) Kaiser Family Foundation $25,000 Jul to Jun Kaiser Experiences and Attitudes in Prenatal Testing (Nunes, Co-I) Stanford Center for Integration of Research on Genetics and Ethics (CIRGE) $50,000 Jun to Jun William L. Nyhan, MD, PhD Mutational Analysis and Molecular Studies of HPRT Deficiency (Nyhan, PI) Lesch-Nyhan Syndrome Children s Research Foundation $50,000 / year Tariq Rana, PhD Mechanisms of innate immunity against HIV (Rana, PI) NIH/NIAID R01 AI $1,160,000 Feb to Jan Structure and Function of Ribonucleoprotein Complexes Modulating HIV Replication (Rana, PI) NIH/NIAID R01 AI $1,035,000 Jul to Jun Preclinical Development of HIV-1 VIF Antagonists (Rana, PI) NIH/NIMH P01 MH $1,435,000 Aug to Jul Computational Design of Inhibitor Specificity (Rana, PI) NIH/NIGMS R01 GM $404,000 Jun to May 2018 Innate Immune Responses and Vaccines Against Tumor-Associated Herpesviruses (Rana, PI) NIH/NCI P01 CA $1,170,00 0 Sep to Aug Regulation of HIV infection by Methamphetamine and non-coding RNAs (Rana, PI) NIH/NIDA R01 DA $1,290,000 Jul to Feb Modeling HIV/AIDS Associated Neurological Disorders with Pluripotent Cells (Rana, PI) NIH/NIDA DP1 DA $2,500,000 Mar to Jan UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 119

61 Genome Information Sciences 120 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 121

62 INTRODUCTION Since its inception in the fall of 2009, the Division of Genome Information Sciences has been actively engaged in both basic and clinical research in the mechanisms of genetic disease. The Division, in the UC San Diego School of Medicine s Department, is comprised of three faculty members, Dr. Kelly Frazer (Division Chief), Dr. Vikas Bansal and Dr. Debashis Sahoo. Dr. Frazer s laboratory is located in the Leichtag Biomedical Sciences Building and works closely with physicians in the Department, Moores UCSD Cancer Center, UCSD Clinical and Translational Research Institute, Sulpizio Cardiovascular Center, and Rady Children s Hospital. Dr. Bansal s and Dr. Sahoo s laboratories are located at the Rady Children s Hospital campus and the School of Medicine Biomedical Research Facility II (BRF2). FACULTY Nearly $1 million in research support 122 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report DIVISION FAST FACTS The Division is actively engaged in both clinical and research in the mechanisms of genetic disease MAJOR PLANS AND GOALS To continue with the Division's highly collaborative research, engaging in a wide variety of clinical and basic science research to further the understanding, treatment, and cure of disorders To expand its clinical and research activities through collaborations with research clinicians within the UC San Diego Health System To expand the Division's multi-disciplinary studies, allowing for data collection and analysis of large numbers of samples Kelly A. Frazer, PhD Professor Division Chief Director of UCSD Institute for Genomic Medicine Vikas Bansal, PhD Assistant Professor The Division is involved with individual mentoring as well as classroom instruction. Dr. Sahoo currently teaches CSE100 and directs a postdoctorate researcher in his laboratory. Dr. Bansal currently mentors a graduate student from the Department of Computer Science & Engineering (CSE) and is a thesis committee member for students in Bioinformatics and Systems Biology (BISB) Graduate Program and Biomedical Sciences (BMS) Graduate Program. He has also served as a mentor for an undergraduate student in the RSRI Program at UCSD. In collaboration with Dr. Vineet Bafna from CSE, Dr. Bansal is preparing an online course 'Analyze The main function of this division is to use genomic data as a basis for focusing on the predisposition for complex diseases. Their research aims to understand genetic predisposition to disease and the mechanism of expressed genotype to phenotype. Results of this research may result in patientspecific treatments and the evolution of personalized medicine in the future. Kelly Frazer, PhD Dr. Frazer s laboratory examines the influence of human genetic variation in disease, including the identification of rare variants that may predispose individuals to disease, and the gene networks regulating gene expression in disease. The laboratory also develops and validates bioinformatics analysis pipelines for the analysis of whole genome sequences, RNA transcriptomes, and epigenomes. Her laboratory s research spans a wide spectrum of disease, including cardiovascular diseases such as long QT syndrome and cardiomyopathy, Type 2 diabetes, chronic lymphocytic leukemia (CLL), breast cancer, retinal dystrophies, and ovarian cancer. Notably, her laboratory has developed a computational pipeline for using transcriptome sequencing data (RNA-seq) for the discovery of mrna isoforms specifically expressed in tumors, in collaboration with Dr. Cheryl Saenz at the Moores Cancer Center. The overall goal of this research is to identify mrna TEACHING ACTIVITIES Debashis Sahoo, PhD Assistant Professor your Genome' for a CSE MS program with specialization in Biological Data Sciences. Dr. Frazer currently directs five post doctorate researchers and three graduate students in her laboratory. The graduate students represent these UCSD training programs: Bioinformatics and Systems Biology (BISB), Biomedical Informatics (BI) National Library of Medicine Fellowship, and the Genetics Training Program (GTP). Each academic quarter she mentors graduate students from the Biomedical Sciences (BMS) Graduate Program for lab rotations and serves on multiple graduate student thesis committees. RESEARCH ACTIVITIES isoforms present specifically in ovarian tumor cells, which would allow for the development of early tumor detection assays. In addition, through a collaboration with Dr. John- Bjarne Hansen at the University of Tromsø (Norway), Dr. Frazer s laboratory has conducted targeted sequencing and array genotyping of 1200 individuals and are analyzing these data to identify genetic risk factors and rare gene variation in the etiology of venous thromboembolism (VTE), a common disease resulting in deep-vein thrombosis and pulmonary embolism. A large part of the Frazer laboratory is involved in the NextGen Program of the National Human Genome Research Institute (NHGRI) and the Heart, Lung, and Blood Institute (NHLBI), which is aimed at generating and utilizing ipsc to investigate the biological mechanisms underlying disease association with genetic variants. Dr. Frazer s laboratory has specifically been funded to link cardiac molecular phenotypes to genotypes through the generation of ipsc-derived cardiomyocytes from 222 individuals in the CARDiPS collection. The subjects in CARDiPS largely consist of normal healthy individuals as well as individuals with cardiovascular diseases. With these samples we hope to identify inherited coding and regulatory variants that influence gene expression and the epigenome landscape in both ipscs and the corresponding derived cardiomyocytes Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 123

63 Vikas Bansal, PhD Dr. Bansal s laboratory investigates human genetic variation and its role in disease using a combination of high-throughput DNA sequencing, bioinformatics, statistics and large scale data analysis. The laboratory is developing computational methods and tools to accurately detect mutations such as insertions/ deletions from whole genome and exome sequencing. His laboratory is also developing statistical methods for analyzing the association of rare variants identified from large-scale sequencing projects with complex diseases such as diabetes. Debashis Sahoo, PhD Dr. Sahoo s laboratory develops new methods to analyze highthroughput biological datasets. His laboratory has developed several tools and techniques to analyze large collections of microarray datasets, which allow for informed specific biological predictions in gene exion to better understand the process of differentiation in normal and cancer tissues. PUBLICATIONS Kelly Frazer, PhD and Lab Manolio, TA, Chisholm RL, Ozenberger B, Roden DM, Williams MS, Wilson R, Bick D, Bottinger EP, Brilliant MH, Eng C, Frazer KA, Korf B, Ledbetter DH, Lupski JR, Marsh C, Mrazek D, Murray MF, O'Donnell PH, Rader DJ, Relling MV, Shuldiner AR, Valle D, Weinshilboum R, Green ED, Ginsburg GS (2013) Implementing genomic medicine in the clinic: the future is here. Genetics in Medicine. 15: Jiang Q, Crews LA, Barrett CL, Chun HJ, Court AC, Isquith JM, Zipeto MA, Goff DJ, Minden M, Sadarangani A, Rusert JM, Dao KH, Morris SR, Goldstein LS, Marra MA, Frazer KA, Jamieson CH (2013) ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia. Proceedings of the National Academy of Sciences. 110(3): Goff DJ, Recart AC, Sadarangani A, Chun HJ, Barrett CL, Krajewska M, Leu H, Low-Marchelli J, Ma W, Shih AY, Wei J, Zhai D, Geron I, Pu M, Bao L, Chuang R, Balaian L, Gotlib J, Minden M, Martinelli G, Rusert J, Dao KH, Shazand K, Wentworth P, Smith KM, Jamieson CA, Morris SR, Messer K, Goldstein LS, Hudson TJ, Marra M, Frazer KA, Pellecchia M, Reed JC, Jamieson CH (2013) A Pan- BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition. Cell Stem Cell. 12(3): Yost SE, Pastorino S, Rozenzhak S, Smith EN, Chao YS, Frazer KA, et al. (2013) High-Resolution Mutational Profiling Suggests the Genetic Validity of Glioblastoma Patient-Derived Pre-Clinical Models. PLoS ONE. 8(2): e Barrett CL, Schwab RB, Jung H, Crain B, Goff DJ, Frazer KA, et al. (2013) Transcriptome Sequencing of Tumor Subpopulations Reveals a Spectrum of Therapeutic Options for Squamous Cell Lung Cancer. PLoS ONE. 8(3): e Yost SE, Alakus H, Matsui H, Schwab RB, Jepsen K, Frazer KA, Harismendy O (2013) Mutascope: sensitive detection of somatic mutations from deep amplicon sequencing. Bioinformatics May 27: 29(15) DeBoever C, Reid EG, Smith EN, Wang X, Dumaop W, Harismendy O, Carson D, Richman D, Masliah E, Frazer KA (2013) Whole Transcriptome Sequencing Enables Discovery and Analysis of Viruses in Archived Primary Central Nervous System Lymphomas. PLoS ONE. 8(9): e Zhou D, Udpa N, Ronen R, Stobdan T, Liang J, Appenzeller O, Zhao HW, Yin Y, Du Y, Guo L, Cao R, Wang Y, Jin X, Huang C, Jia W, Cao D, Guo G, Gamboa JL, Villafuerte F, Callacondo D, Xue J, Liu S, Frazer KA, Li Y, Bafna V, Haddad G (2013) Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness in andean highlanders. American Journal of Human Genetics. 93(3): He G, Dhar D, Nakagawa H, Font-Burgada J, Ogata H, Jiang Y, Shalapour S, Seki E, Yost SE, Jepsen K, Frazer KA, Harismendy O, Hatziapostolou M, Iliopoulos D, Suetsugu A, Hoffman RM, Tateishi R, Koike K, Karin M (2013) Evaluation of Ultra-Deep Targeted Sequencing for Personalized Breast Cancer Care. Breast Cancer Research. 15(6):R115. Harismendy O, Schwab RB, Alakus H, Yost SE, Matsui H, Hasteh F, Wallace AM, Park HL, Madlensky L, Parker B, Carpenter PM, Jepsen K, Anton-Culver H, Frazer KA (2013) Evaluation of Ultra-Deep Targeted Sequencing for Personalized Breast Cancer Care. Breast Cancer Research Dec 10; 15(6):R115. Smith EN, Jepsen K, Arias AD, Shepard PJ, Chambers CD, Frazer KA (2014) Genetic ancestry of participants in the National Children's Study. Genome Biology. 15(2):R22. Udpa N, Ronen R, Zhou D, Liang J, Stobdan T, Appenzeller O, Yin Y, Du Y, Guo L, Cao R, Wang Y, Jin X, Huang C, Jia W, Cao D, Guo G, Claydon VE, Hainsworth R, Gamboa JL, Zibenigus M, Zenebe G, Xue J, Liu S, Frazer KA, Li Y, Bafna V, Haddad GG (2014) Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes. Genome Biology. 15:R36. Shlush L, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, Kennedy JA, Schimmer AD, Schuh AC, Yee KW, McLeod JL, Doedens M, Medeiros JJ, Marke R, Kim HJ, Lee K, McPherson JD, Hudson TJ; Frazer KA, Smith, EN, HALT Pan-Leukemia Gene Panel Consortium, Brown AM, Trinh QM, Stein LD, Minden MD, Wang JC, Dick JE (2014) Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 506(7488): Mraz M, Chen L, Rassenti LZ, Ghia EM, Li H, Jepsen K, Smith EN, Messer K, Frazer KA, Kipps TJ (2014) MicroRNA-150 contributes to the proficiency of B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1 genes. Blood. 124(1): Carson AR, Smith EN, Matsui H,Brækkan SK, Jepsen K, Hansen JB, Frazer KA (2014) Effective filtering strategies to improve data quality from population-based whole exome sequencing studies. BMC Bioinformatics. 15 (125): Cheng CP, DeBoever C, Frazer KA, Liu YC, Tseng VS (2014) MiningABs: mining associated biomarkers across multi-connected gene expression datasets. BMC Bioinformatics. 15(1):173. Alakus H, Babicky ML, Ghosh P, Yost S, Jepsen K, Dai Y, Arias A, Samuels ML, Mose ES, Schwab RB, Peterson MR, Lowy AM, Frazer KA, Harismendy O (2014) Genome-wide mutational landscape of mucinous carcinomatosis peritonei of appendiceal origin. Genome Med. 6(5):43. Alakus H, Bollschweiler E, Hölscher AH, Warnecke-Eberz U, Frazer KA, Harismendy O, Lowy AM, Mönig SP, Eberz PM, Maus M, Drebber U, Siffert W, Metzger R (2014) Homozygous GNAS 393C-Allele Carriers with Locally Advanced Esophageal Cancer Fail to Benefit from Platinum-Based Preoperative Chemoradiotherapy. Ann Surg Oncol. 21(13): Cheng CP, Kuo IY, Alakus H, Frazer KA, Harismendy O, Wang YC, Tseng VS (2014) Network-based analysis identifies epigenetic biomarkers of esophageal squamous cell carcinoma progression. Bioinformatics. pii: btu433. Smith EN, Jepsen K, Khosroheidari M, Rassenti LZ, D Antonio M, Ghia EM, Carson DA, Jamieson C, Kipps TJ, Frazer KA (2014) Biased estimates of clonal evolution and subclonal heterogeneity can arise from PCR duplicates in deep sequencing experiments. Genome Biology. 15(8):420. Shepard PJ, Barshop BA, Baumgartner MR, Hansen JB, Jepsen K, Smith EN, Frazer KA (2014) Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD. Genetics in Medicine /gim Crews LA, Jiang Q, Zipeto MA, Lazzari E, Court AC, Ali S, Barrett CL, Frazer KA, Jamieson CH (2015) An RNA editing fingerprint of cancer stem cell reprogramming. J Transl Med. 13(1):52. DeBoever C, Ghia EM, Shepard PJ, Rassenti L, Barrett CL, Jepsen K, Jamieson CH, Carson D. Kipps TJ, Frazer KA (2015) Transcriptome Sequencing Reveals Potential Mechanism of Cryptic 3 Splice Site Selection in SF3B1-mutated Cancers. PLoS Computational Biology. 11 (3), e e Hashem SI, Perry CN, Bauer M, Han S, Clegg SD, Ouyang K, Deacon DC, Spinharney M, Panopoulos AD, Izpisua Belmonte JC, Frazer KA, Chen J, Gong Q, Zhou Z, Chi NC, Adler ED (2015) Oxidative Stress Mediates Cardiomyocyte Apoptosis in a Human Model of Danon Disease and Heart Failure. Stem Cells. doi: / stem Smith EN, Ghia EM, DeBoever CM, Rassenti LZ, Jepsen K, Yoon KA, Matsui H, Rozenzhak S, Alakus H, Shepard PJ, Dai Y, Khosroheidari M, Bina M, Gunderson KL, Messer K, Muthuswamy L, Hudson TJ, Harismendy O, Barrett CL, Jamieson CH, Carson DA, Kipps TJ, Frazer KA (2015) Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development. Blood Cancer. J 5: e303. Alakus H, Yost SE, Woo B, French R, Lin GY, Jepsen K, Frazer KA, Lowy AM, Harismendy O (2015) BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma. J Transl Med. 13(1):122. Barrett CL, DeBoever C, Jepsen K, Saenz CC, Carson DA, Frazer KA (2015) Systematic transcriptome analysis reveals tumor-specific isoforms for ovarian cancer diagnosis and therapy. Proc Natl Acad Sci U S A. 112(23):E doi: /pnas Bao L, Messer K, Schwab R, Harismendy O, Pu M, Crain B, Yost SE, Frazer KA, Rana B, Hasteh F, Wallace A, Parker BA (2015) Mutational Profiling Can Establish Clonal or Independent Origin in Synchronous Bilateral Breast and Other Tumors. PLoS One. 10(11) e Holm F, Hellqvist E, Mason CN, Ali SA, Delos-Santos N, Barrett CL, Chun HJ, Minden MD, Moore RA, Marra MA, Runza V, Frazer KA, Sadarangani A, Jamieson CH (2015) Reversion to an embryonic alternative splicing program enhances leukemia stem cell selfrenewal. Proc Natl Acad Sci U S A. 112(50): doi: / pnas Mimori T, Nariai N, Kojima K, Takahashi M, Ono A, Sato Y, Yamaguchi-Kabata Y, Nagasaki M. isvp: an integrated structural variant calling pipeline from high-throughput sequencing data. (2013) BMC Syst Biol. 7 Suppl 6:S8 Nariai N, Hirose O, Kojima K, Nagasaki M. TIGAR: transcript isoform abundance estimation method with gapped alignment of RNA-Seq data by variational Bayesian inference. (2013) Bioinformatics. 29(18): Kojima K, Nariai N, Mimori T, Takahashi M, Yamaguchi-Kabata Y, Sato Y, Nagasaki M. A statistical variant calling approach from pedigree information and local haplotyping with phase informative reads. (2013) Bioinformatics. (22): Nariai N, Kojima K, Mimori T, Sato Y, Kawai Y, Yamaguchi-Kabata Y, Nagasaki M. TIGAR2: sensitive and accurate estimation of transcript isoform expression with longer RNA-Seq reads. (2014) BMC Genomics. 15 Suppl 10:S5. Nariai N, Kojima K, Saito S, Mimori T, Sato Y, Kawai Y, Yamaguchi- Kabata Y, Yasuda J, Nagasaki M. HLA-VBSeq: accurate HLA typing at full resolution from whole-genome sequencing data. (2015) BMC Genomics. 16 Suppl 2:S7. Mimori T, Nariai N, Kojima K, Sato Y, Kawai Y, Yamaguchi-Kabata Y, Nagasaki M. Estimating copy numbers of alleles from populationscale high-throughput sequencing data. (2015) BMC Bioinformatics. 16 Suppl 1:S4. Kawai Y, Mimori T, Kojima K, Nariai N, Danjoh I, Saito R, Yasuda J, Yamamoto M, Nagasaki M. Japonica array: improved genotype imputation by designing a population-specific SNP array with 1070 Japanese individuals. (2015) J Hum Genet. 60(10): Nagasaki M, Yasuda J, Katsuoka F, Nariai N, Kojima K, Kawai Y, Yamaguchi-Kabata Y, Yokozawa J, Danjoh I, Saito S, Sato Y, Mimori T, Tsuda K, Saito R, Pan X, Nishikawa S, Ito S, Kuroki Y, Tanabe O, Fuse N, Kuriyama S, Kiyomoto H, Hozawa A, Minegishi N, Douglas Engel J, Kinoshita K, Kure S, Yaegashi N; ToMMo Japanese Reference Panel Project, Yamamoto M. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. (2015) Nat Commun. 6:8018. doi: /ncomms9018. Andreassen OA, Smith EN, Psychiatric Genomics Consortium (PGC), Dale AM. (2013) Improved Detection of Common Variants Associated with Schizophrenia and Bipolar Disorder Using Pleiotropy-Informed Conditional False Discovery Rate. PLoS genetics 9: e (The Psychiatric Genomics Consortium (PGC) is composed of approximately 200 researchers, including Dr. Smith) Demerath EW, Liu C-T, Franceschini N, Chen G, Palmer JR, Smith EN, Chen CT, Ambrosone CB, Arnold AM, Bandera EV (2013) Genome-wide association study of age at menarche in African- American women. Human molecular genetics. 22(16): Ganesh SK, Smith EN, Asselbergs FW, et al. (2013) Loci influencing blood pressure identified using a cardiovascular gene-centric array. Human molecular genetics. 22: Greenwood TA, Smith EN, Bipolar Genome Study (BiGS) Consortium, Kelsoe JR (2013) Genome-Wide Association Study of Irritable vs. Elated Mania Suggests Genetic Differences between Clinical Subtypes of Bipolar Disorder. PloS One. 8: e (The Bipolar Genome Study Consortium (BiGS) is composed of approximately 50 researchers, including Dr. Smith) Schork AJ, Smith EN, The Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, The Schizophrenia Psychiatric Genomics Consortium, Schork NJ, Dale AM (2013) All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs. PLoS genetics. 9: e (The Bipolar Disorder Working Group of the Psychiatric Genomics Consortium is composed of approximately 175 researchers, including Dr. Smith) Cross-Disorder Group of the Psychiatric Genomics Consortium, Smith EN, Smoller JW, Craddock N, Kendler K, Lee PH, Neale BM, Nurnberger JI, Ripke S, Santangelo S, Sullivan PF (2013) Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 381: (The Cross-Disorder Group of the Psychiatric Genomics Consortium (PGC) is composed of approximately 350 researchers, including Dr. Smith) Lee SH, Smith EN, Wray NR, et al. (2013) Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature genetics. 45: Scott-Van Zeeland AA, Smith EN, Carson A, Topol EJ, Shih PB, Magistretti P, Bergen AW, Berrettini W, Kaye W, Schork NJ, et al. (2013) Evidence for the role of EPHX2 gene variants in anorexia nervosa. Molecular psychiatry. 19(6): Cousminer DL, Smith EN, The ReproGen Consortium, Widen E, et al. for the Early Growth Genetics (EGG) Consortium (2013) Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. Human molecular genetics. 22: UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 125

64 (The ReproGen Consortium is composed of approximately 175 researchers, including Dr. Smith) Perry JR, Smith EN, Murray A, et al. (2013) DNA mismatch repair gene MSH6 implicated in determining age at natural menopause. Human molecular genetics. 23(9): Ruderfer DM, Smith EN, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Kendler KS, et al. (2013) Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. Mol Psychiatry. Yoneyama S, Smith EN, Taylor KC, et al. (2014) Gene-centric metaanalyses for central adiposity traits in up to individuals of European descent confirm known loci and reveal several novel associations. Human molecular genetics. 23(9): Tragante V, Smith EN, Keating BJ, et al. (2014) Gene-centric Metaanalysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci. American Journal of human genetics. 94(3): Shlush LI, Smith EN, Consortium HP-LGP, Dick JE, et al. (2014) Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 506: (The Consortium HP-LGP is composed of approximately 41 researchers, including Dr. Smith) Andreassen OA, Smith EN, The Psychiatric Genomics Consortium (PGC) Bipolar Disorder and Schizophrenia Work Groups, Dale AM, et al. (2014) Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci. Mol Psychiatry. 20(2): (The Bipolar Disorder Working Group of the Psychiatric Genomics Consortium is composed of approximately 175 researchers, including Dr. Smith) Nurnberger JI, Jr., Koller DL, Jung J, Edenberg HJ, Foroud T, Guella I, Vawter MP, Kelsoe JR, Smith EN, Psychiatric Genomics Consortium Bipolar Group (2014) Identification of pathways for bipolar disorder: a meta-analysis. JAMA Psychiatry. 71: (The Psychiatric Genomics Consortium (PGC) is composed of approximately 200 researchers, including Dr. Smith) Arking DE, Smith EN, CARe Consortium, COGENT Consortium, Newton-Cheh C, et al. (2014) Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization. Nat Genet. 46(8): (The CARe-COGENT Consortiums are composed of approximately 53 researchers, including Dr. Smith) Maier R, Smith EN, Cross-Disorder Working Group of the Psychiatric Genomics Consortium, Lee SH, Cross-Disorder Working Group of the Psychiatric Genomics Consortium, et al. (2015) Joint Analysis of Psychiatric Disorders Increases Accuracy of Risk Prediction for Schizophrenia, Bipolar Disorder, and Major Depressive Disorder. Am J Hum Genet. 96(2): The Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium (2015) Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nat Neurosci. 18: Locke AE, Smith EN, The ReproGen Consortium, Speliotes EK, et al. (2015) Genetic studies of body mass index yield new insights for obesity biology. Nature. 518: Shungin D, Smith EN, The ReproGen Consortium, Mohlke KL, et al. (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature. 518: Maier R, Smith EN, Cross-Disorder Working Group of the Psychiatric Genomics Consortium, Lee SH, et al. (2015) Joint Analysis of Psychiatric Disorders Increases Accuracy of Risk Prediction for Schizophrenia, Bipolar Disorder, and Major Depressive Disorder. Am J Hum Genet. 96(2): Anand A, Koller DL, Lawson WB, Gershon ES, Nurnberger JI, Smith EN, BiGS Collaborative (2015) Genetic and childhood trauma interaction effect on age of onset in bipolar disorder: An exploratory analysis. J Affect Disord. 179: 1-5. Swaminathan S, Koller DL, Foroud T, Edenberg HJ, Xuei X, Niculescu AB, 3rd, Smith EN, Bipolar Genome Study (BiGS) Consortium, Nurnberger JI, Jr. (2015) Characteristics of Bipolar I patients grouped by externalizing disorders. J Affect Disord. 178: Vikas Bansal, PhD and Lab Selvaraj S, Dixon JR, Bansal V, Ren B. (2013) Whole genome haplotype reconstruction using proximity-ligation and shotgun sequencing. Nat Biotechnol. 31(12): Scott-Van Zeeland AA, Bloss C, Tewhey C, Bansal V, et al. (2013) Evidence for the role of EPHX2 gene variants in Anorexia Nervosa. Mol Psychiatry. 19(6): Bansal V, Libiger O. Fast individual ancestry inference from DNA sequence data leveraging allele frequencies for multiple populations. BMC Bioinformatics Jan 16;16:4. Debashis Sahoo, PhD and Lab Voskoboynik A, Neff NF, Sahoo D, Newman AM, Pushkarev D, Koh W, Passarelli B, Fan HC, Mantalas GL, Palmeri KJ, Ishizuka KJ, Gissi C, Griggio F, Ben-Shlomo R, Corey DM, Penland L, White RA 3rd, Weissman IL, Quake SR (2013) The genome sequence of the colonial chordate, Botryllus schlosseri. Elife. 2:e Chan CK, Lindau P, Jiang W, Chen JY, Zhang LF, Chen CC, Seita J, Sahoo D, Kim JB, Lee A, Park S, Nag D, Gong Y, Kulkarni S, Luppen CA, Theologis AA, Wan DC, DeBoer A, Seo EY, Vincent-Tompkins JD, Loh K, Walmsley GG, Kraft DL, Wu JC, Longaker MT, Weissman IL (2013) Clonal precursor of bone, cartilage, and hematopoietic niche stromal cells. Proc Natl Acad Sci U S A. 110(31): Voskoboynik A, Newman AM, Corey DM, Sahoo D, Pushkarev D, Neff NF, Passarelli B, Koh W, Ishizuka KJ, Palmeri KJ, Dimov IK, Keasar C, Fan HC, Mantalas GL, Sinha R, Penland L, Quake SR, Weissman IL (2013) Identification of a Colonial Chordate Histocompatibility Gene. Science. 341(6144): Dimov IK, Lu R, Lee EP, Seita J, Sahoo D, Park SM, Weissman IL, Lee LP (2014) Discriminating cellular heterogeneity using microwellbased RNA cytometry. Nat Commun. 5:3451. Shin K, Lim A, Zhao C, Sahoo D, Pan Y, Spiekerkoetter E, Liao JC, Beachy PA (2014) Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors. Cancer Cell. 26(4): Pan Y, Volkmer JP, Mach KE, Rouse RV, Liu JJ, Sahoo D, Chang TC, Metzner TJ, Kang L, van de Rijn M, Skinner EC, Gambhir SS, Weissman IL, Liao JC (2014) Endoscopic molecular imaging of human bladder cancer using a CD47 antibody. Sci Transl Med. 6(260):260ra148. doi: /scitranslmed Scheeren FA, Kuo AH, van Weele LJ, Cai S, Glykofridis I, Sikandar SS, Zabala M, Qian D, Lam JS, Johnston D, Volkmer JP, Sahoo D, van de Rijn M, Dirbas FM, Somlo G, Kalisky T, Rothenberg ME, Quake SR, Clarke MF (2014) A cell-intrinsic role for TLR2-MYD88 in intestinal and breast epithelia and oncogenesis. Nat Cell Biol. 16(12): doi: /ncb3058. Chan CK, Seo EY, Chen JY, Lo D, McArdle A, Sinha R, Tevlin R, Seita J, Vincent-Tompkins J, Wearda T, Lu WJ, Senarath-Yapa K, Chung MT, Marecic O, Tran M, Yan KS, Upton R, Walmsley GG, Lee AS, Sahoo D, Kuo CJ, Weissman IL, Longaker MT (2015) Identification and Specification of the Mouse Skeletal Stem Cell. Cell. 160(1-2): Cheah MT, Chen JY, Sahoo D, Contreras-Trujillo H, Volkmer AK, Scheeren FA, Volkmer JP, Weissman IL (2015) CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer. Proc Natl Acad Sci U S A. 112(15): GRANT AND RESEARCH SUPPORT Kelly Frazer, PhD U01 HL (PI) 07/ /2016 $9,551,900 NIH (NHLBI) Regulatory Genomic Studies in a Cohort of ips Cell Derived Cardiomyocytes P30 CA (PI) 05/ /2019 $1,129,000 NIH (NCI) Specialized Cancer Center Support Grant, Genomics and Bioinformatics Shared Resource P30 CA (Core Director) 05/ /2019 $1,129,000 NIH (NCI) Specialized Cancer Center Support Grant, Genomics and Bioinformatics Shared Resource (PI) 07/ /2018 $1,870,800 K.G. Jebsen Medical Foundation (Norway)/Thrombosis Research and Expertise Centre (TREC) Venous Thrombosis Embolism R41 HG A1 (PI) 03/ /2017 $230,000 NIH (NHGRI - Arima Genomics) Optimizing HaploSeq for Whole-Genome Phased Haplotypes in Biomedical Applications (PI) 04/ /2020 $1,462,190 U01 DK NIH (NIDDK - Ludwig Institute) Functional Analysis of T2D Associated Non-Coding SNPs GC1R B (PI) 04/ /2018 $243,345 CESCG CRP CIRM (Salk Institute) Functional Genomics of Drug-Induced Electrophysiological Phenotypes in Human Cardiomyocytes: A Population Study (PI) 05/ /2016 $1,660 Auggie Babbitt Ovarian Cancer Research Fund Angelo Arias, Post doctorate Researcher HL S1 (PI) 09/ /2016 $334,315 NIH (NHLBI) Regulatory Genomic Studies in a Cohort of ips Cell Derived Cardiomyocytes Ricardo Armisen, PhD FONDEF D11I1029 (PI) 12/ /2016 $677,248 Incorporación de la secuenciación de ultima generación en el cuidado de los pacientes con cáncer. (FONDEF D11I1029 of public interest "Incorporating next generation sequencing into the care of cancer patients.") Christian Barrett, PhD (Barrett, PI) 09/ /2014 $120,000 Sponsored Research Tanabe Research Labs, USA Discovery of mrna isoforms specifically expressed in clear cell renal cell carcinoma Christian Barrett, PhD (Barrett, PI) 01/ /2014 $25,600 Colleen s Dream Foundation Kicking for the Dream Kelly Frazer, PhD 8 UL1 TR (Gary Firestein) 07/01/ /31/2014 San Diego Clinical and Translational Research Institute (CTRI) Kelly Frazer, PhD DR (Carson, Dennis) 03/01/ /28/2014 $151,000 California Institute for Regenerative Medicine Development of Highly Active Anti-Leukemia Stem Cell Therapy (HALT) (Frazer, Key Personnel) Paola Benaglio, Post doctorate Researcher (Key Personnel) 06/ /2015 $70,650 Swiss National Science Foundation The Effect of Human Genetic Variants on the Regulation of Cardiac Gene Expression Vikas Bansal, PhD R21 HG / /2016 $260,505 NIH Methods for detecting short indels from high-throughput sequence data (Bansal, PI) Vikas Bansal, PhD (Key Personnel) 10/ /2014 $320,842 Discovery Innovation Grant, Sanofi-Aventis and University of Ulm, Germany Population sequencing of genomic regions associated with risk of Type 2 Diabetes (Bansal, PI) Debashis Sahoo, PhD R00 CA / /2017 $463,524 NIH Application of Boolean Networks to discover stem and progenitor cells (Sahoo, PI) Debashis Sahoo, PhD BCAN Bladder Cancer Advocacy Network (BCAN) 05/ /2015 $89,304 High Resolution Molecular Analysis of CD47-mediated immune escape in bladder cancer (Sahoo, PI) Debashis Sahoo, PhD 1K99CA (Project 47597) 07/ /2014 $304,270 NIH Application of Boolean networks to discover stem and progenitor cells (Sahoo, PI) 126 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 127

65 Heart Institute (Cardiology & Cardiothoracic Surgery) 128 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 129

66 INTRODUCTION Rady Children s Heart Institute was created to integrate and coordinate the clinical, research and educational programs of the Cardiology and Cardiovascular Surgery Divisions at RCHSD. FACULTY (CARDIOLOGY) The division of Cardiology currently includes 19 full time cardiologists. Recruitments since July 2013 include: Dr. Singh, the Medical Director of Heart Failure and Transplantation, Dr. Yeh, the Medical Director of the Cardiovascular ICU, Dr. Williams an expert in Electrophysiology and Pacing, Dr. Vaughn, an expert in Heart Failure and Transplantation, Dr. Do, an expert in cardiac intensive care, and Dr. Sah, a general cardiologist who will receive additional training in Cardiac Imaging as a junior faculty member. Dr. Ratnayaka an interventional cardiologist and expert in interventional MR was also recruited will join the faculty in early Currently, there are active recruitments underway for two additional experts in cardiovascular intensive care and an expert in cardiac imaging. DIVISION FAST FACTS John W. Moore, MD, MPH Professor of Clinical Pediatrics; Division Chief Christopher Davis, MD, PhD Associate Clinical Professor ; Director of Cardiac Clinic and Exercise Laboratory, Thomas Do, MD Assistant Clinical Professor, Cardiovascular Intensive Care Unit Howaida G. El-Said, MD, PhD Clinical Professor ; Director of Cardiac Catheterization Laboratory Brian T. Fagan, MD Assistant Clinical Professor 6 Heart Transplants in 2015 with 100% survival Only comprehensive tertiary care in the San Diego Region MAJOR PLANS AND GOALS Jeffrey R. Frazer, MD Associate Clinical Professor ; Directorof Pulmonary Hypertension, RCHSD Paul D. Grossfeld, MD Clinical Professor ; Director of Pediatric Cardiology Fellowship Program Sanjeet Hegde, MD, PhD Assistant Clinical Professor ; Academic Director of Cardiac MRI Rachel McCandless, MD Staff Physician Delaram Molkara, MD Associate Clinical Professor ; Clinical Director of Fetal Cardiology, RCHSD Successfully completed the recruitment of a third pediatric cardiothoracic surgeon, who is expected to begin operating on site in November We have recently added additional cardiology faculty with strong expertise in fetal echo and cardiac MRI Funding for and are in the process of physician recruitment for leadership positions in Cardiac Transplantation and Cardiac Critical Care Vishal Nigam, MD Assistant Professor in Residence James C. Perry, MD Professor of Clinical Pediatrics; Medical Director of Electrophysiology, Pacing and Adult Congenital Heart Disease Beth Printz, MD, PhD Associate Professor of Clinical Pediatrics, Associate Professor of Radiology; Medical Director of Non-Invasive Cardiac Imaging Kanishka Ratnayaka, MD Staff Physician; Interventional Cardiac MRI; Interventional Pediatric Cardiology Serena Sah, MD Staff Physician Completed the installation of and are currently actively using a dedicated pediatric Cardiac MRI Scanner and a new state of the art dedicated Pediatric Cardiac Catheterization Laboratory. We are also working in our new cardiac operating room. We have opened a dedicated Cardiovascular Intensive Care Unit (CVICU), and we are on the verge of moving into an expanded, new Heart Center Administrative and Board of Directors approval in place to establish an in-house pediatric heart transplant program associated with the UCSD adult program. We are in process of submitting our UNOS application for cardiac transplantation with the long range goal of adding a program in lung transplantation Rakesh Singh, MD Assistant Clinical Professor ; Medical Director of Heart Failure and Transplantation, RCHSD Heather Sun, MD Assistant Clinical Professor ; Academic director of Fetal Cardiology, RCHSD Gabrielle Vaughn, MD Assistant Clinical Professor Matthew Williams, MD Associate Clinical Professor ; Director of Pacing Justin Yeh, MD Associate Clinical Professor ; Director of CVICU 130 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 131

67 David Aurigemma, MD Mohammad Ebrahim, MD Jesse Lee, MD FACULTY (CARDIAC SURGERY) ( John J. Lamberti, MD Professor of Surgery, Chief of Cardiac Surgery at RCHSD, Eugene and Joye Klein Director of the RCHSD Heart Institute FELLOWS The Division is the only comprehensive tertiary care provider of cardiovascular services in the region (San Diego, Imperial, and South Orange Counties), and it receives referrals from Balboa Naval Medical Center, as well as the San Diego Regional Kaiser Medical Center. In addition, the Division is the major off-island referral center for the State of Hawaii. The Division s clinical volumes for the academic year were average inpatient census of 26 patients, total outpatient visits of 17,244 including patients seen in satellite offices. The echocardiography laboratory performed 12,048 echocardiograms. There were 620 cardiac catheterizations performed, about 70% of which were interventional catheterizations; and there were 259 cardiac MRI s performed. In the last five years there has been steady growth in all categories. The growth of the Division's clinical volumes has been related to our increased scope of services (addition of Heart Failure and Transplantation), expanding referral practice within Southern California and neighboring states, as well as to meeting previously unmet demand for services within the traditional referral regions. The Division s clinical volumes place the program among the largest pediatric and congenital heart disease centers in the United States. CLINICAL PROGRAMS The cardiology outpatient programs moved into the newly remodeled outpatient Heart Center which occupies approximately half of the first floor of Rose Pavilion opened in March The Center contains 13 exam rooms, 6 echocardiography rooms, 3 ECG/ Holter rooms, the exercise testing laboratory, and multiple offices for administrative and clinical personnel. Total outpatient cardiology visits were 17,244 in In addition to general cardiology clinics, specialty clinics include Adult Congenital, Heart Failure/Transplant, Pulmonary Hypertension, Preventive Cardiology, Electrophysiology/ Pacemaker, and Kawasaki Disease. At full capacity, there are 6 cardiovascular physicians seeing patients during clinic sessions. Cardiology outpatients are also seen at the five Rady Children s Hospital satellite offices. Cardiology patients are scheduled 5 days per month in Murrieta, 4 days per month in Oceanside, 3 days per month in Encinitas, 2 days per month in El Centro, and 2 days per month in Escondido. Echocardiography is available in Murrieta and Encinitas, and there are plans to extend to the other clinics once 132 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Eric J. Devaney, MD Associate Professor of Surgery, Director of Cardiac Transplantation and Assist Devices at RCHSD Rachel Moore, MD Raghav Murthy, MD Jose Silva Sepulveda, MD CARDIOLOGY CLINICAL ACTIVITIES staffing of sonographers permits. Since 2013, there has been a steady growth in the inpatient services provided by the Cardiology Division. The Acute Cardiac Unit (ACU), a 30 bed unit in the Rose Pavilion of Rady Children s Hospital, was opened in August 2013 with the goal of providing inpatient care to pediatric patients with both acquired and congenital heart disease. Initially, care was provided by three separate services: cardiology, critical care, and neonatology with each service functioning independently of the others. Beginning in 2015, this care model evolved to incorporate an integrated approach that stresses teamwork and collaborative care amongst all three disciplines. Patients receive care from admission to discharge in a single area to optimize continuity. A full spectrum of services is provided including: acute care, cardiac critical care, and mechanical circulatory support (ECMO and ventricular assist devices). Since opening the average daily ACU census has steadily grown, and the heart transplant program was launched with 6 transplants performed in There has also been a progressive increase in patient complexity which has grown out of both the developing heart failure program and the congenital surgical population, reflecting Rady Children s role as a major referral center. In line with this rise in patient complexity, the number of patients supported by mechanical circulatory support has increased in 2015 with 20 patients supported on ECMO and one patient supported by a ventricular assist device. Despite this rise in complexity, the ACU has continued to provide excellent patient outcomes. The Cardiac Catheterization Program has continued to increase reaching a total of more than 600 annually. This case volume represents extraordinary utilization of a single catheterization laboratory. The complexity risk of our cases have on average has exceeded that of other pediatric catheterization laboratories according to IMPACT Registry data. Despite elevated risks our riskadjusted adverse event rates have remained low, and this has been accomplished with very low radiation dose compared to national norms (IMPACT Registry data). In partnership with Rady Children s Hospital, we are planning a second catheterization laboratory/mr suite where procedures will be done partially or completely under real-time MRI guidance (IMR Laboratory). We have successfully recruited Dr Kanishka Ratnayaka, who is a pioneer in that field to help us with this endeavor. For the first time in RCHSD/UCSD history, the Electrophysiology Program has two fully-trained and certified pediatric electrophysiologists on staff. Dr. Matthew Williams returned from an extra year of Program. The addition of Dr. Williams has allowed the Division to increase the EP training at Children s Hospital Boston to join Dr. James Perry. Dr. Williams brings additional expertise and insight into electro-anatomic mapping systems and will begin by directing the EP Pacing and Device number of EP procedures, adding an additional slot in the lab each week, with our increased focus on Adult CHD arrhythmia substrates. The Hawaii Heart Week EP Program continues to provide catheter ablations for an average of 22 patients each year in Honolulu along with outpatient visits each year. Prior to 2014, all pediatric patients needing heart transplantation were referred to institutions outside of San Diego. This required families to temporarily move out of San Diego, leading to disruption of lives and separation of the patient from home, parents and community for months to years. San Diego s first comprehensive Pediatric Heart Transplantation program officially opened at Rady Children s Hospital in late 2014 after successfully receiving Centers for Medicare and Medicaid Services (CMS) and United Network of Organ Sharing (UNOS) regulatory approval. The first pediatric heart transplant surgery at Rady Children s Hospital was performed on January 14, 2015, followed by 5 other transplantations in Our survival rate is 100%, with these patients being followed closely in a unique multi-disciplinary transplant clinic staffed by transplant cardiologists, transplant NP/RNs, social workers, dieticians, child life specialists, and transplant pharmacists. In addition to the heart transplantation program, a new Ventricular Assist Device (VAD) program was established at Rady Children s Hospital San Diego to help sustain our sickest patients on artificial heart machines. Our first VAD implantation was on April 9, 2015, with this patient successfully being bridged to transplantation. The ability to provide VAD support for children with end-stage heart The Division provides a comprehensive accredited educational program for fellowship training in pediatric cardiology. Dr. Grossfeld is the Fellowship Program Director, and the Program is supported by all of the faculty/staff. Fellows are offered clinical teaching and men The Division provides a comprehensive accredited educational program for fellowship training in pediatric cardiology. Dr. Grossfeld is the Fellowship Program Director, and the Program is supported by all of the faculty/staff. Fellows are offered clinical teaching and mentoring in all aspects of clinical cardiology: Outpatient care and evaluation, Inpatient and ICU care, Echocardiography, CT and MRI, Diagnostic and Interventional Cardiac Catheterization, Electrophysiology and Pacing, Exercise Physiology and Clinical Research. A broad schedule of lectures and presentations are offered including: Weekly Surgery Conference, Weekly Catheterization Conference, Weekly Core Lecture, and Monthly Journal Club and Research Meeting. The three-year program has full ACGME accreditation. The program currently has five ACGME approved positions. In addition, the program currently offers fourth year training positions in interventional cardiology, non-invasive imaging, electrophysiology, and cardiac development. Four of our current fellows are extending their training through these fourth year training opportunities. The Division offers a fourth year position for an Advanced Fellow in interventional congenital cardiology. This position includes training and experience as operator or first assistant in a minimum of 250 procedures, teaching conferences, and training in clinical research. failure has allowed us to keep these patients alive as we wait for a donor heart. Adult Congenital Heart Disease was officially recognized as a Subspecialty by the ABIM in The first certification exam in Adult Congenital Heart Disease was administered in October of Dr. James Perry and Dr. Howaida El-Said passed that exam and are the only Board certified Adult CHD Specialists in San Diego, Imperial and Riverside Counties. Dr. Perry was one of 6 faculty for the first ACHD exam study session, given at the ACC Heart House before the exam. RCHSD/UCSD now is positioned as one of the only 2 centers west of the Mississippi to have two Board certified ACHD cardiologists on staff. Plans in ACHD for 2016 include a formal application for accreditation as an ACHD ACHA Comprehensive Care Center, filing for an ACHD fellowship to begin in 2017 and outpatient clinic space at Sulpizio CV Center. The Division had 934 outpatient visits for patients 18 and older in FY The non-invasive Cardiac Imaging Program at RCHSD/UCSD, including both echocardiography and cardiac MRI, has grown significantly. In the echo lab, over 12,000 echocardiograms were performed in 2015, which is an increase of approximately 10% year-to-year, and we have seen an increase of approximately 25% in echocardiography volume over the past 3 years. Fetal echocardiography volume has particularly increased, with more studies performed at RCHSD as well as at UCSD. For cardiac MRI, over 250 studies were performed in 2015, approximately 20% more than the prior year; cardiac MRI volume has increased approximately 40% over the past 3 years. The Divisin is now looking toward expanding sonographer and physician staffing to match this increase in non-invasive imaging volume. Dr Ratnayaka, who recently joined the Division, has plans in conjunction with RCHSD/ UCSD to initiate an interventional cardiac MRI program that decreases and can even eliminate the need for ionizing radiation to perform certain cardiac procedures on children and young adults with congenital heart disease. Dr. Ratnayaka has been one of the pioneers in the field working previously at the National Institutes of Health. TEACHING ACTIVITIES Faculty/staff cardiologists are also active in training of pediatric residents and medical students. Rotation in pediatric cardiology is not mandatory for residents, but many selected the one month Pediatric Cardiology elective designed by Dr. Perry. This selective provides both inpatient and outpatient experiences. Dr. Davis participates as an Instructor in the Clinics course required for second year medical students. As part of its mission to advance the care of pediatric patients with heart disease through education, the Heart Institute at Rady Children s Hospital sponsored an international medical conference entitled Innovations in Pediatric Heart Failure from December 3-5, 2015 in San Diego, CA. This state-of-the-art, interactive program brought together over 50 nationally recognized experts from 25 institutions, including many faculty members from Rady Children s Hospital and UCSD. The format of the conference was unique and included didactic sessions, expert panels, and debates on the most controversial topics in the field of pediatric heart failure. The conference was attended by over 250 medical professionals, making it the largest pediatric heart failure national meeting to date Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 133

68 Paul Grossfield, MD Dr. Grossfeld s laboratory investigates the genetic basis of congenital heart defects in Jacobsen Syndrome (11q-). His research has led to the identification of the ETS-1 gene as a cause of heart defects in 11q-. Using animal model systems, his research has determined that loss of ETS-1 causes impaired cardiac neural crest cell migration, likely due to impaired contact inhibition of locomotion, as the cause of conotruncal heart defects in 11q-. This coincides with a change of cell fate from cardiac neural crest cells to cardiac myocytes. In addition, recent evidence has implicated a critical role for ETS-1 in regulating cardiac myocyte numbers during normal heart development. Loss of ETS-1 in a developing frog heart causes a dramatic increase in cardiac myocyte number with a concomitant loss of endocardial cells, resulting in a hypoplastic left heart syndrome-like phenotype. Dr. Grossfeld was recently awarded a prestigious Grant-In-Aid grant from the American Heart Association to continue to support this research. This past year Dr. Grossfeld and his collaborators have identified the RICS (ARHGAP32) gene as a cause of autism in 11q-. Studies in genetically engineered mice have demonstrated that treatment with a commonly used anti-anxiety mediation, Clonazepam, ameliorates the autistic features in these mice, hopefully leading to a clinical trial on people with 11q- and autism in the near future. Vashal Nigam, MD Dr. Nigam s laboratory continues to make significant progress towards improving the understanding the pathogenesis of Hypoplastic Left Heart Syndrome (HLHS) and identifying potential novel treatments for this very severe congenital heart defects. The lab continues to be focused on elucidating the role of biomechanical stimuli play in normal and pathologic cardiac development. In the past year, the lab reported the novel finding that exposure to cyclic stretch is sufficient to increase proliferation and growth of embryonic cardiomyocytes. Currently, the lab is in the process of reporting a microrna that is sufficient to increase cardiomyocyte proliferation in newborn mice. In addition, the lab in conjunction with Drs. Omens and McCulloch s laboratories has developed the first finite element model that has the potential to predict the left ventricular growth of human fetuses. Based upon this research progress, the National Institutes of Health (NIH) is awarding Dr. Nigam an R01 grant. Dr. Nigam will be one of the few Pediatric Cardiologists in the country with a basic/translational science R01. James Perry, MD Dr. Perry s research spans a wide range of electrophysiology and congenital heart disease. Research, abstracts and publications reflect collaborative efforts with cardiology, pharmacology, aerospace and mechanical engineering and bioengineering colleagues. Dr. Perry s translational research work continues in the area of computational modeling of single ventricle physiology: an R01 was successfully obtained ( The Cardiac Atlas Project ) and continues with Drs. McCulloch and Omens of UCSD Bioengineering. This grant encompasses all aspects of myocardial performance from the cell to the macro level in generating models of CHD that can be both predictive of new views of congestive failure and also manipulated to study the effects of interventions before they are done. Studies of intraventricular flow related to different electrophysiologic states continue with Dr. Del Alamo of UCSD Mechanical and Aerospace Engineering. Christopher Davis, MD, PhD Congenital Heart Surgeons Society (CHSS) Determining the Natural and Unnatural History of Anomalous Aortic Origin of a Coronary Artery with Interarterial or Intraconal or Intramural Course (AAOCA): Establishing a Multi-Institutional Registry (DC) Noninvasive measurement of cardiac output using impedance RESEARCH ACTIVITIES cardiography in patients with congenital heart disease (CT) Outcome of patients with one-and-a half ventricles: a comparative assessment of cardiac function, exercise tolerance, morbidity, and mortality (R) Thomas Do, MD The fate of the liver late following Fontan palliation:correlation of non-invasive liver assessment with liver biopsy and with cardiac status as measured by cardiac MRI and by catheterization-obtained hemodynamics (CT) Howaida El-Said, MD, PhD ADO II Clinical Study Closure of Atrial Septal Defects with the AMPLATZER Septal Occluder (ASO) Post Market Surveillance Study (CT) Closure of Muscular Ventricular Defects with the Amplatzer Muscular VSD Occluder Post Approval Study (VPA) (CT) Coarctation of the Aorta Stent Trial (COAST) Phase I (CT) Congenital Cardiac Catheterizations Project on Outcomes (C3PO) Quality Improvement Registry (QI) Congenital Cardiac Catheterization Outcomes Project Quality Improvement (C3PO-QI) Radiation Project (QI) Continued Access to Covered Cheatham-Platinum Stent for Prevention or Treatment of Aortic Wall injuries Associated with Aortic Coarctation Continued Access (COAST II CA) (CT) Correlation of Magnetic Resonance Elastography with Transjugular Hepatic Biopsy in Fontan Patients (R) Covered Cheatham-Platinum Stent for Prevention or Treatment of Aortic Damus-Kaye Stansel (DKS) Surgical Procedure: Long-term Followup of Survivors and Analysis of Possible Sequelae (R) Damus-Kaye Stansel (DKS) Surgical Procedure: Quality of Life After DKS (DC) Examining the Effect of Introducer Sheath Length on Incidence of Arterial Occlusion in Pediatric Femoral Artery Cardiac Catheterizations (R) Examining the Effect of Introducer Sheath Length on Incidence of Arterial Occlusion in Pediatric Femoral Artery Cardiac Catheterizations Part II (R) I mmediate, Short, and Intermediate-term Effects of Balloon:Annulus Ratio on Pressure Gradient Change on Incidence of Pulmonary Regurgitation Implantation of the Medtronic Melody Transcatheter Pulmonary Valve (TPV) in Patients with Dysfunctional Right Ventricular Outflow Tract (RVOT) Melody valve implantation a single center study; outcome, complications and technical aspects (R) NCDR - American College of Cardiology IMPACT Registry (QI) Pulmonary Artery Repair with Covered Stents (PARCS): The Use of Covered Cheatham Platinum Stents for Repair of Right Ventricular to Pulmonary Single center experience comparing the use of transthoracic echocardiography (TTE) versus transesophageal echocardiography (TEE) for guidance of Amplatzer Septal Occluder (ASO) device placement in trans-catheter atrial septal defect closure (ASD) in children (R) The fate of the liver late following Fontan palliation:correlation of non-invasive liver assessment with liver biopsy and with cardiac status as measured by cardiac MRI and by catheterization-obtained hemodynamics (CT) The Role of Cardiac Catheterization Following Single Ventricle Surgical Palliation: Characteristics and Outcomes Part II (R) Transcatheter Outcomes of Stenting of Blalock-Taussig Shunts and Congenital Heart Disease (R) Brian Fagan, MD Congenital Cardiac Catheterizations Project on Outcomes (C3PO) 134 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 135

69 Quality Improvement Registry (QI) Congenital Cardiac Catheterization Outcomes Project Quality Improvement (C3PO-QI) Radiation Project (QI) Jeffrey Frazer, MD Outcomes in Preterm and Low Birthweight Newborns Undergoing Cardiac Surgery Outcomes in Preterm and Low-birthweight Newborns Undergoing Cardiac Surgery Part II (R) Paul Grossfeld, MD Cardiovascular and Musculoskeletal Assessment of Elite U.S. Volleyball Players (CS) Sanjeet Hegde, MD, PhD SPKLS002: Echocardiographic Assessment of Cardiac Left Ventricular Strain, Torsion The Cardiac Atlas Project (DC) Delaram Molkara, MD Single center experience comparing the use of transthoracic echocardiography (TTE) versus transesophageal echocardiography (TEE) for guidance of Amplatzer Septal Occluder (ASO) device placement in trans-catheter atrial septal defect closure (ASD) in children (R) Value of Ventricular Outflow Tract Imaging in Prenatal Diagnosis of Congenital Heart Disease (R) Modeling Hemodynamic Stresses in Congenital Heart Disease (R) John W. Moore, MD, MPH ADO II Clinical Study (CT) Closure of Atrial Septal Defects with the AMPLATZER Septal Occluder (ASO) Post Market Surveillance Study (CT) Closure of Muscular Ventricular Defects with the Amplatzer Muscular VSD Occluder Post Approval Study (VPA) (CT) Coarctation of the Aorta Stent Trial (COAST) Phase I (CT) Congenital Cardiac Catheterizations Project on Outcomes (C3PO) Quality Improvement Registry (QI) Congenital Cardiac Catheterization Outcomes Project Quality Improvement (C3PO-QI) Radiation Project (QI) Continued Access to Covered Cheatham-Platinum Stent for Prevention or Treatment of Aortic Wall injuries Associated with Aortic Coarctation Correlation of Magnetic Resonance Elastography with Trans-jugular Hepatic Biopsy in Fontan Patients (R) Covered Cheatham-Platinum Stent for Prevention or Treatment of Aortic Examining the Effect of Introducer Sheath Length on Incidence of Arterial Occlusion in Pediatric Femoral Artery Cardiac Catheterizations (R) Examining the Effect of Introducer Sheath Length on Incidence of Arterial Occlusion in Pediatric Femoral Artery Cardiac Catheterizations Part II Immediate, Short, and Intermediate-term Effects of Balloon:Annulus Ratio on Pressure Gradient Change on Incidence of Pulmonary Regurgitation Following Balloon Valvuloplasty (R) Implantation of the Medtronic Melody Transcatheter Pulmonary Valve (TPV) in Patients with Dysfunctional Right Ventricular Outflow Tract (RVOT) Conduits: A Post Market Approval Study (CT) Melody valve implantation a single center study; outcome, complications and technical aspects (R) Melody valve implantation a single center study; outcome, complications and technical aspects Retrospective Chart Review Part II (R) NCDR - American College of Cardiology IMPACT Registry (QI) Pulmonary Artery Repair with Covered Stents (PARCS): The Use of Covered Cheatham Platinum Stents for Repair of Right Ventricular to Pulmonary Single center experience comparing the use of transthoracic echo cardiography (TTE) versus transesophageal echocardiography (TEE) for guidance of Amplatzer Septal Occluder (ASO) device placement in trans-catheter atrial septal defect closure (ASD) in children (R) The Role of Cardiac Catheterization Following Single Ventricle Surgical Palliation: Characteristics and Outcomes (R) The Role of Cardiac Catheterization Following Single Ventricle Surgical Palliation: Characteristics and Outcomes Part II (R) Transcatheter Outcomes of Stenting of Blalock-Taussig Shunts and Ductus Arteriosus: A single center review Part II (R) Vishal Nigam, MD Profiling of Tissues from Patients with Congenital Heart Defects Modeling Hemodynamic Stresses in Congenital Heart Disease Retrospective Profiling of Hypoplastic Left Heart Ventricular Tissue The Damus-Kaye Stansel (DKS) Surgical Procedure: Quality of Life After DKS The Damus-Kaye Stansel (DKS) Surgical Procedure: Long-term Follow-up of Survivors and Analysis of Possible Sequelae MRI Imaging, Echocardiographic Imaging, and Computational Simulation of Cardiovascular Physiology (DC) Outcomes in Preterm and Low-birthweight Newborns Undergoing Cardiac Surgery (R) Outcomes in Preterm and Low-birthweight Newborns Undergoing Cardiac Surgery Part II (R) The Cardiac Atlas Project (DC) James Perry, MD Congenital Cardiac Catheterizations Project on Outcomes (C3PO) Quality Improvement Registry (QI) Congenital Cardiac Catheterization Outcomes Project Quality Improvement (C3PO-QI) Radiation Project (QI) Damus-Kaye Stansel (DKS) Surgical Procedure: Quality of Life After DKS (DC) International Cohort Study on Cardiac Rhythm and Conduction Disorder in Discordant Atrio-Ventricular Connection (DISCO Study) (DC) MRI Imaging, Echocardiographic Imaging, and Computational Simulation of Cardiovascular Physiology (DC) SPKLS002: Echocardiographic Assessment of Cardiac Left Ventricular Strain, Torsion The Cardiac Atlas Project (DC) Wolff-Parkinson-White Syndrome and Sudden Death: A Multi-Center, Retrospective Assessment of WPW Patients Presenting with Atrial Fibrillation, Sudden Death or Aborted Sudden Death (DC) Beth Printz, MD, PhD SPKLS002: Echocardiographic Assessment of Cardiac Left Ventricular Strain, Torsion and Blood Flow Analysis in Subjects with Congenital and Acquired Heart Disease Assessing the Association between Entrustable Professional Activities (EPAs), Competencies, and Milestones in the Pediatric Subspecialties (ED) Evaluating the updated techniques in multi-detector computed tomography to assess congenital heart disease in the pediatric population (R) Implantation of the Medtronic Melody Transcatheter Pulmonary Valve (TPV) in Patients with Dysfunctional Right Ventricular Outflow Tract (RVOT) Conduits: A Post Market Approval Study MRI Imaging, Echocardiographic Imaging and Computational Simulation of Cardiovascular Physiology (DC) Single center experience comparing the use of transthoracic echocardiography (TTE) versus transesophageal echocardiography (TEE) for guidance of Amplatzer Septal Occluder (ASO) device placement in trans-catheter atrial septal defect closure (ASD) in children (R) The Cardiac Atlas Project (DC) The fate of the liver late following Fontan palliation:correlation of non-invasive liver assessment with liver biopsy and with cardiac status as measured by cardiac MRI and by catheterization-obtained hemodynamics (CT) PUBLICATIONS John W. Moore, MD, MPH Vincent RN, Moore J, Beekman RH, Benson L, Bergersen L, Holzer R, Jayaram N, Jenkins K, Ringel R, Rome J, Martin GR. Procedural characteristics and adverse events in diagnostic and interventional catheterisations in paediatric and adult CHD: initial report from the IMPACT Registry. Cardiol Young 2016;26: El-Said HG, Ebrahim M, Moore JW. Left main coronary artery stenting in a 3.6 kg infant after arterial switch operation for transposition of the great arteries. Ann Pediatr Cardiol 2015;8: Mallula K, Vaughn G, El-Said H, Lamberti JJ, Moore JW. Comparison of ductal stenting versus surgical shunts for palliation of patients with pulmonary atresia and intact ventricular septum. Catheter Cardiovasc Interv 2015;85: Moore JW, Vincent RN, Beekman RH, Benson L, Bergersen L, Holzer R, Jayaram N, Jenkins K, Li Y, Ringel R, Rome J, Martin GR. Procedural results and safety of common interventional procedures in congenital heart disease: initial report from the national cardiovascular data registry. J Am Coll Cardiol 2014;64: Moore JW, Greene J, Palomares S, Javois A, Owada CY, Cheatham JP, Hoyer MH, Jones TK, Levi DS. Results of the Combined U.S. Multicenter Pivotal Study and the Continuing Access Study of the Nit-Occlud PDA Device for Percutaneous Closure of Patent Ductus Arteriosus. JACC Cardiovasc Interv 2014;7: Armstrong AK, Balzer DT, Cabalka AK, Gray RG, Javois AJ, Moore JW, Rome JJ, Turner DR, Zellers TM, Kreutzer J. One-year followup of the melody transcatheter pulmonary valve multicenter postapproval study. JACC Cardiovasc Interv 2014;7: Bartakian S, El-Said HG, Printz B, Moore JW. Prospective randomized trial of transthoracic echocardiography versus transesophageal echocardiography for assessment and guidance of transcatheter closure of atrial septal defects in children using the Amplatzer septal occluder. JACC Cardiovasc Interv 2013;6: Lin CH, Hegde S, Marshall AC, Porras D, Gauvreau K, Balzer DT, Beekman RH, Torres A, Vincent JA, Moore JW, Holzer R, Armsby L, Bergersen L. Incidence and management of life-threatening adverse events during cardiac catheterization for congenital heart disease. Pediatr Cardiol 2014;35: Bratincsák A, Moore JW, El-Said HG. Low dose tissue plasminogen activator treatment for vascular thrombosis following cardiac catheterization in children: a single center experience. Catheter Cardiovasc Interv 2013;82: Holzer RJ, Gauvreau K, Kreutzer J, Moore JW, McElhinney DB, Bergersen L. Relationship between procedural adverse events associated with cardiac catheterization for congenital heart disease and operator factors: results of a multi-institutional registry (C3PO). Catheter Cardiovasc Interv 2013;82: Backes CH, Cua C, Kreutzer J, Armsby L, El-Said H, Moore JW, Gauvreau K, Bergersen L, Holzer RJ. Low weight as an independent risk factor for adverse events during cardiac catheterization of infants. Catheter Cardiovasc Interv 2013;82: El-Said H, Hegde S, Moore J. First Report of Atretic Coronary Sinus Stenting in a 5-kg Infant Resulting in Dramatic Improvement of Ventricular Function in Functional Single Ventricle. Congenit Heart Dis 2014;3;9:E Learn CP, Holzer RJ, Daniels CJ, Torres AJ, Vincent JA, Moore JW, Armsby LB, Landzberg MJ, Bergersen L. Adverse events rates and risk factors in adults undergoing cardiac catheterization at pediatric hospitals--results from the C3PO. Catheter Cardiovasc Interv 2013;81: Christopher Davis, MD, PhD Tedjasaputra V, Sá RC, Arai TJ, Holverda S, Theilmann RJ, Chen WT, Wagner PD, Davis CK, Kim Prisk G, Hopkins SR. The heterogeneity of regional specific ventilation is unchanged following heavy exercise in athletes. J Appl Physiol 2013;115: Law W, DiBardino DJ, Raviendren R, Devaney E, Davis C. Anomalous aortic origin of the left coronary artery: in-hospital cardiac arrest and death despite bed rest. World J Pediatr Congenit Heart Surg 2014;5: Thomas Do, MD Do, Scheurer, Atz. Book Chapter: Palliative Procedures In: Pediatric Critical Care Medicine: Basic Science and Clinical Evidence, 2nd Edition. Springer-Verlag, 2014 Authors: Derek Wheeler, Hector Wong, Thomas Shanley. Butts, Do, Atz. Book Chapter: Standard Monitoring Techniques in the Pediatric Cardiac ICU Chapter pgs In: Pediatric and Congenital Cardiology, Cardiac Surgery and Intensive Care, 2nd Edition. Springer-Verlag, 2014 Authors: Eduardo Cruz, Victor Hraska, Dunbar Ivy, James Jagger Howaida El-Said, MD, PhD El-Said HG, Ebrahim M, Moore JW. Left main coronary artery stenting in a 3.6 kg infant after arterial switch operation for transposition of the great arteries. Ann Pediatr Cardiol 2015;8: DiBardino DJ, Gomez-Arostegui J, Kemp A, Raviendran R, Hegde S, Devaney EJ, Lamberti JJ, El-Said H. Intermediate Results of Hybrid Versus Primary Norwood Operation. Ann Thorac Surg 2015;99: Mallula K, Vaughn G, El-Said H, Lamberti JJ, Moore JW. Comparison of ductal stenting versus surgical shunts for palliation of patients with pulmonary atresia and intact ventricular septum. Catheter Cardiovasc Interv 2015;85: Ebrahim M, Hagood J, Moore J, El-Said H. Bronchoscopic guidance of endovascular stenting limits airway compression. Catheter Cardiovasc Interv 2015;85: El-Said H, Hegde S, Foerster S, Hellenbrand W, Kreutzer J, Trucco SM, Holzer R, Burch G, Mirani A, Nicolas R, Porras D, Bergersen L, Moore J. Device therapy for atrial septal defects in a multicenter cohort: Acute outcomes and adverse events. Catheter Cardiovasc Interv 2015;85: Bratincsak A, Moore JW, Gulker B, Choules B, Koren L, El-Said HG. Breaking the limit: mechanical characterization of overexpanded balloon expandable stents used in congenital heart disease. Congenit Heart Dis 2015;10: El-Said HG, Bratincsak A, Foerster SR, Murphy JJ, Vincent J, Holzer R, Porras D, Moore J, Bergersen L. Safety of percutaneous patent ductus arteriosus closure: an unselected multicenter population experience. J Am Heart Assoc 2013;2:e Bartakian S, El-Said HG, Printz B, Moore JW. Prospective randomized trial of transthoracic echocardiography versus transesophageal echocardiography for assessment and guidance of transcatheter closure of atrial septal defects in children using the Amplatzer septal occluder. JACC Cardiovasc Interv 2013;6: Bratincsák A, Moore JW, El-Said HG. Low dose tissue plasminogen activator treatment for vascular thrombosis following cardiac catheterization in children: a single center experience. Catheter Cardiovasc Interv 2013;82: UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 137

70 El-Said H, Hegde S, Moore J. First Report of Atretic Coronary Sinus Stenting in a 5-kg Infant Resulting in Dramatic Improvement of Ventricular Function in Functional Single Ventricle. Congenit Heart Dis 2013;9:E Moore J, Hegde S, El-Said H, Beekman R, Benson L, Bergersen L, Holzer R, Jenkins K, Ringel R, Rome J, Vincent R, Martin G. Transcatheter device closure of atrial septal defects: a safety review. JACC Cardiovasc Interv 2013;6: Backes CH, Cua C, Kreutzer J, Armsby L, El-Said H, Moore JW, Gauvreau K, Bergersen L, Holzer RJ. Low weight as an independent risk factor for adverse events during cardiac catheterization of infants. Catheter Cardiovasc Interv 2013;82: Jeff Frazer, MD Sato YZ, Molkara DP, Daniels LB, Tremoulet AH, Shimizu C, Kanegaye JT, Best BM, Snider JV, Frazer JR, Maisel A, Burns JC. Cardiovascular biomarkers in acute Kawasaki disease. Int J Cardiol Mar 20;164(1): doi: /j.ijcard Epub 2011 Jul 20. PubMed PMID: ; PubMed Central PMCID: PMC Paul Grossfeld, MD Glidewell SC, Miyamoto SD, Grossfeld PD, Clouthier DE, Coldren CD, Stearman RS, Geraci MW. Transcriptional Impact of Rare and Private Copy Number Variants in Hypoplastic Left Heart Syndrome. Clin Transl Sci 2015;8: Davis CK, Dyar DA, Vargas LA, Grossfeld PD. Cardiovascular and Musculoskeletal Assessment of Elite US Volleyball Players. Clin J Sport Med 2015;25: Favier R, Akshoomoff N, Mattson S, Grossfeld P. Jacobsen syndrome: Advances in our knowledge of phenotype and genotype. Am J Med Genet C Semin Med Genet 2015;169: Akshoomoff N, Mattson SN, Grossfeld PD. Evidence for autism spectrum disorder in Jacobsen syndrome: identification of a candidate gene in distal 11q. Genet Med 2015;17: Ye M, Parente F, Li X, Perryman MB, Zelante L, Wynshaw-Boris A, Chen J, Grossfeld P. Gene-targeted deletion of OPCML and Neurotrimin in mice does not yield congenital heart defects. Am J Med Genet A 2014;164: Dr. Sanjeet Hegde DiBardino DJ, Gomez-Arostegui J, Kemp A, Raviendran R, Hegde S, Devaney EJ, Lamberti JJ, El-Said H. Intermediate Results of Hybrid Versus Primary Norwood Operation. Ann Thorac Surg 2015;99: El-Said H, Hegde S, Foerster S, Hellenbrand W, Kreutzer J, Trucco SM, Holzer R, Burch G, Mirani A, Nicolas R, Porras D, Bergersen L, Moore J. Device therapy for atrial septal defects in a multicenter cohort: Acute outcomes and adverse events. Catheter Cardiovasc Interv 2015;85: DiBardino DJ, Hegde S, Lamberti JJ. Further insight into a rare pathology: differential aspects of left ventricular diverticulum. World J Pediatr Congenit Heart Surg 2014;5: Hegde S, Moore J. Reply: Cardiac perforation by atrial septal defect closure devices: a potentially catastrophic and still unclear event. JACC Cardiovasc Interv 2014;7: Lin CH, Hegde S, Marshall AC, Porras D, Gauvreau K, Balzer DT, Beekman RH, Torres A, Vincent JA, Moore JW, Holzer R, Armsby L, Bergersen L. Incidence and management of life-threatening adverse events during cardiac catheterization for congenital heart disease. Pediatr Cardiol 2014;35: El-Said H, Hegde S, Moore J. First Report of Atretic Coronary Sinus Stenting in a 5-kg Infant Resulting in Dramatic Improvement of Ventricular Function in Functional Single Ventricle. Congenit Heart Dis. 2013;9:E Moore J, Hegde S, El-Said H, Beekman R, Benson L, Bergersen L, Holzer R, Jenkins K, Ringel R, Rome J, Vincent R, Martin G. Transcatheter device closure of atrial septal defects: a safety review. JACC Cardiovasc Interv 2013;6: Delaram Molkara, MD Sato YZ, Molkara DP, Daniels LB, Tremoulet AH, Shimizu C, Kanegaye JT, Best BM, Snider JV, Frazer JR, Maisel A, Burns JC. Cardiovascular biomarkers in acute Kawasaki disease. Int J Cardiol Mar 20;164(1): doi: /j.ijcard Epub 2011 Jul 20. PubMed PMID: ; PubMed Vishal Nigam, MD Patel V, Carrion K, Hollands A, Hinton A, Gallegos T, Dyo J, Sasik R, Leire E, Hardiman G, Mohamed SA, Nigam S, King CC, Nizet V, Nigam V. The stretch responsive microrna mir-148a-3p is a novel repressor of IKBKB, NF-?B signaling, and inflammatory gene expression in human aortic valve cells. FASEB J 2015;29: Banerjee I, Carrion K, Serrano R, Dyo J, Sasik R, Lund S, Willems E, Aceves S, Meili R, Mercola M, Chen J, Zambon A, Hardiman G, Doherty TA, Lange S, Del Álamo JC, Nigam V. Cyclic stretch of embryonic cardiomyocytes increases proliferation, growth, and expression while repressing Tgf-ß signaling. J Mol Cell Cardiol 2015;79: Lathen C, Zhang Y, Chow J, Singh M, Lin G, Nigam V, Ashraf YA, Yuan JX, Robbins IM, Thistlethwaite PA. ERG-APLNR Axis Controls Pulmonary Venule Endothelial Proliferation in Pulmonary Veno-Occlusive Disease. Circulation 2014;130: Carrion K, Dyo J, Patel V, Sasik R, Mohamed SA, Hardiman G, Nigam V. The Long Non-Coding HOTAIR Is Modulated by Cyclic Stretch and WNT/ß-CATENIN in Human Aortic Valve Cells and is a Novel Repressor of Calcification Genes. PLoS One 2014;9:e Johnson TD, Dequach JA, Gaetani R, Ungerleider J, Elhag D, Nigam V, Behfar A, Christman KL. Human versus porcine tissue sourcing for an injectable myocardial matrix hydrogel. Biomater Sci 2014;60283D. Szeto K, Pastuszko P, Alamo JC, Lasheras J, Nigam V. Bicuspid aortic valves experience increased strain as compared to tricuspid aortic valves. World J Pediatr Congenit Heart Surg 2013;4: Krishnamurthy A, Villongco CT, Chuang J, Frank LR, Nigam V, Belezzuoli E, Stark P, Krummen DE, Narayan S, Omens JH, McCulloch AD, Kerckhoffs RC. Patient-Specific Models of Cardiac Biomechanics. J Comput Phys 2013;244:4-21. Tejman-Yarden S, Levi O, Beizerov A, Parmet Y, Nguyen T, Saunders M, Rudich Z, Perry JC, Baker DG, Moeller-Bertram T. Heart rate analysis by sparse representation for acute pain detection. Med Biol Eng Comput 2016;54: Tejman-Yarden S, Bratincsak A, Bachner-Hinenzon N, Khamis H, Rzasa C, Adam D, Printz BF, Perry JC. Left Ventricular Mechanical Property Changes During Acute AV Synchronous Right Ventricular Pacing in Children. Pediatr Cardiol 2016;37: James Perry, MD Kung E, Perry JC, Davis C, Migliavacca F, Pennati G, Giardini A, Hsia TY, Marsden A. Computational modeling of pathophysiologic responses to exercise in Fontan patients. Ann Biomed Eng 2015;43: Bratincsák A, Williams M, Kimata C, Perry JC. The Electrocardiogram Is a Poor Diagnostic Tool to Detect Left 138 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 139

71 Ventricular Hypertrophy in Children: A Comparison with Echocardiographic Assessment of Left Ventricular Mass. Congenit Heart Dis 2015;10:E Khairy P, Van Hare GF, Balaji S, Berul CI, Cecchin F, Cohen MI, Daniels CJ, Deal BJ, Dearani JA, Groot Nd, Dubin AM, Harris L, Janousek J, Kanter RJ, Karpawich PP, Perry JC, Seslar SP, Shah MJ, Silka MJ, Triedman JK, Walsh EP, Warnes CA. PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: Developed in Partnership Between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the Governing Bodies of PACES, HRS, the American College of Cardiology (ACC), the American Heart Association (AHA), the European Heart Rhythm Association (EHRA), the Canadian Heart Rhythm Society (CHRS), and the International Society for Adult Congenital Heart Disease (ISACHD). Can J Cardiol 2014;30:E1-63. Chao T, Perry JC, Romanowski GL, Tremoulet AH, Capparelli EV. Optimizing pediatric esmolol dosing using computerized practitioner order entry. J Pediatr Pharmacol Ther 2014;19: Williams MR, Shepard SM, Boramanand NK, Lamberti JJ, Perry JC. Long-term follow-up shows excellent transmural atrial lead performance in patients with complex congenital heart disease. Circ Arrhythm Electrophysiol 2014;7: Beth Printz, MD, PhD Numano F, Shimizu C, Tremoulet AH, Dyar D, Burns JC, Printz BF. Pulmonary Artery Dilation and Right Ventricular Function in Acute Kawasaki Disease. Pediatr Cardiol 2016;37: Tejman-Yarden S, Bratincsak A, Bachner-Hinenzon N, Khamis H, Rzasa C, Adam D, Printz BF, Perry JC. Left Ventricular Mechanical Property Changes During Acute AV Synchronous Right Ventricular Pacing in Children. Pediatr Cardiol 2016;37: Srivastava S, Printz BF, Geva T, Shirali GS, Weinberg PM, Wong PC, Lang P. Task Force 2: Pediatric Cardiology Fellowship Training in Noninvasive Cardiac Imaging: Endorsed by the American Society of Echocardiography and the Society of Pediatric Echocardiography. J Am Soc Echocardiogr 2015;28: Jaggi P, Wang W, Dvorchik I, Printz B, Berry E, Kovalchin JP, Texter K, Ramilo O, Burns JC, Tremoulet AH. Patterns of Fever in Children After Primary Treatment for Kawasaki Disease. Pediatr Infect Dis J 2015;34: Sun HY, Fripp RR, Printz BF. Unusual consequence of a fetal atrial septal aneurysm. Clin Case Rep 2015;3: Srivastava S, Printz BF, Geva T, Shirali GS, Weinberg PM, Wong PC, Lang P. Task Force 2: Pediatric Cardiology Fellowship Training in Noninvasive Cardiac Imaging. J Am Coll Cardiol 2015;66: Srivastava S, Printz BF, Geva T, Shirali GS, Weinberg PM, Wong PC, Lang P; Society of Pediatric Cardiology Training Program Directors; American College of Cardiology; American Academy ; American Heart Association. Task Force 2: Pediatric Cardiology Fellowship Training in Noninvasive Cardiac Imaging. SPCTPD/ ACC/AAP/AHA. Circulation 2015;132:e Printz BF. The 30-year road of noninvasive imaging for congenital aortic stenosis: new insights from cardiac magnetic resonance imaging. J Am Coll Cardiol 2014; Tremoulet AH, Jain S, Jaggi P, Jimenez-Fernandez S, Pancheri JM, Sun X, Kanegaye JT, Kovalchin JP, Printz BF, Ramilo O, Burns JC. Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet 2014;383: Bartakian S, El-Said HG, Printz B, Moore JW. Prospective randomized trial of transthoracic echocardiography versus transesophageal echocardiography for assessment and guidance of transcatheter closure of atrial septal defects in children using the Amplatzer septal occlude. JACC Cardiovasc Interv 2013;6: Selamet Tierney ES, Levine JC, Chen S, Bradley TJ, Pearson GD, Colan SD, Sleeper LA, Campbell MJ, Cohen MS, De Backer J, Guey LT, Heydarian H, Lai WW, Lewin MB, Marcus E, Mart CR, Pignatelli RH, Printz BF, Sharkey AM, Shirali GS, Srivastava S, Lacro RV; Pediatric Heart Network Investigators. Echocardiographic methods, quality review, and measurement accuracy in a randomized multicenter clinical trial of Marfan syndrome. J Am Soc Echocardiog. 2013;26: Kanishka Ratnayaka, MD Rogers T, Ratnayaka K, Schenke WH, Sonmez M, Kocaturk O, Mazal JR, Chen MY, Flugelman MY, Troendle JF, Faranesh AZ, Lederman RJ. Fully percutaneous transthoracic left atrial entry and closure as a potential access route for transcatheter mitral valve interventions. Circ Cardiovasc Interv 2015;8:e Rogers T, Ratnayaka K, Sonmez M, Franson DN, Schenke WH, Mazal JR, Kocaturk O, Chen MY, Faranesh AZ, Lederman RJ. Transatrial intrapericardial tricuspid annuloplasty. JACC Cardiovasc Interv 2015;8: Rogers T, Ratnayaka K, Schenke WH, Faranesh AZ, Mazal JR, O'Neill WW, Greenbaum AB, Lederman RJ. Intentional right atrial exit for microcatheter infusion of pericardial carbon dioxide or iodinated contrast to facilitate sub-xiphoid access. Catheter Cardiovasc Interv 2015;86:E Halabi M, Faranesh AZ, Schenke WH, Wright VJ, Hansen MS, Saikus CE, Kocaturk O, Lederman RJ, Ratnayaka K. Real-time cardiovascular magnetic resonance subxiphoid pericardial access and pericardiocentesis using off-the-shelf devices in swine. J Cardiovasc Magn Reson 2013;15:61. Halabi M, Ratnayaka K, Faranesh AZ, Chen MY, Schenke WH, Lederman RJ. Aortic access from the vena cava for large caliber transcatheter cardiovascular interventions: pre-clinical validation. J Am Coll Cardiol 2013;61: Faranesh AZ, Kellman P, Ratnayaka K, Lederman RJ. Integration of cardiac and respiratory motion into MRI roadmaps fused with x-ray. Med Phys 2013;40: Halabi M, Ratnayaka K, Faranesh AZ, Hansen MS, Barbash IM, Eckhaus MA, Wilson JR, Chen MY, Slack MC, Kocaturk O, Schenke WH, Wright VJ, Lederman RJ. Transthoracic delivery of large devices into the left ventricle through the right ventricle and interventricular septum: preclinical feasibility. J Cardiovasc Magn Reson 2013;15:10. Donofrio MT, Levy RJ, Schuette JJ, Skurow-Todd K, Sten MB, Stallings C, Pike JI, Krishnan A, Ratnayaka K, Sinha P, duplessis AJ, Downing DS, Fries MI, Berger JT. Specialized delivery room planning for fetuses with critical congenital heart disease. Am J Cardiol 2013;111: doi: Ratnayaka K, Faranesh AZ, Hansen MS, Stine AM, Halabi M, Barbash IM, Schenke WH, Wright VJ, Grant LP, Kellman P, Kocaturk O, Lederman RJ. Real-time MRI-guided right heart catheterization in adults using passive catheters. Eur Heart J 2013;34: Rakesh Singh, MD Singh RK. Definition of pediatric heart failure. In: Kirk R, Dipchand A, Rosenthal D, eds. ISHLT Guidelines for the Management of Pediatric Heart Failure. Philadelphia, PA: Lippincott Williams & Wilkins; 2014: Kaddourah A, Goldstein SL, Lipshultz SE, Wilkinson JD, Sleeper LA, Lu M, Colan SD, Succop PA, Towbin JA, Aydin SI, Rossano J, Everitt MD, Gossett JG, Rusconi P, Kantor PF, Singh RK, Jefferies JL. Prevalence, Predictors, and Outcomes of Cardiorenal Syndrome in Children with Dilated Cardiomyopathy: A Report from the Pediatric Cardiomyopathy Registry. Pediatr Nephrol 2015;30: Singh RK, ME Richmond, Zuckerman WA, Lee TM, Giblin TB, Rodriguez R, Chen JM, Addonizio LJ. The use of oral sildenafil for management of right ventricular dysfunction after pediatric heart transplantation. Am J Transplant 2014;14: Everitt MD, Sleeper LA, Lu M, Canter CE, Pahl E, Addonizio L, Singh RK, Lamour J, Webber SA, Colan SD, Margossian R, Kantor PF, Towbin JA, Rossano J, Wilkinson JD, Lipshultz SE. Recovery of Echocardiographic Function in Children with Idiopathic Dilated Cardiomyopathy: Results from the Pediatric Cardiomyopathy Registry. J Amer Coll Cardiol 2014;63: Hahn E, Zuckerman WA, Chen JM, Singh RK, Addonizio LJ, Richmond ME. An Echocardiographic Measurement of SVC to IVC Distance in Patients < 20 Years of Age with Idiopathic Dilated Cardiomyopathy. Amer J Cardiol 2014;113: Yilmaz B, Zuckerman WA, Lee TM, Beddows KD, Gilmore LA, Singh RK, Richmond ME, Chen JM, Addonizio LJ. Left ventricular assist device to avoid heart-lung transplant in an adolescent with dilated cardiomyopathy and severely elevated pulmonary vascular resistance. Pediatr Transplant 2013;17: E Easterwood R, Singh RK, McFeely E, Addonizio LJ, Gilmore L, Beddows K, Chen JM, Richmond ME. Pediatric Cardiac Transplantation Using Hearts Previously Refused for Quality: A Single Center Experience. Am J Transplant 2013;13: Marshall CD, Richmond ME, Singh RK, Gilmore L, Beddows K, Chen JM, Addonizio LJ. A comparison of traditional versus contemporary immunosuppressive regimens in pediatric heart recipients. J Pediatrics 2013;163: Heather Sun, MD Sun HY, Fripp RR, Printz BF. Unusual consequence of a fetal atrial septal aneurysm. Clin Case Rep 2015;3: Sun HY, Behzadian F, Punn R, Tacy TA. Decremental left ventricular deformation after pulmonary artery band training and subsequent repair in ventriculoarterial discordance. J Am Soc Echocardiogr 2013;26: Sun HY, Buccola KJ, Punn R, Silverman NH, Peng LF, Perry SB, Balasubramanian S. Transcatheter device closure of a congenital aortic-left atrial tunnel. Congenit Heart Dis 2014;9:E Truong UT, Sun HY, Tacy TA. Myocardial deformation in the fetal single ventricle. J Am Soc Echocardiogr 2013;26: Sun HY, Boe J, Rubesova E, Barth RA, Tacy TA. Fetal MRI correlates with postnatal CT angiogram assessment of pulmonary anatomy in tetralogy of Fallot with absent pulmonary valve. Congenit Heart Dis 2014;9:E Peng DM, Sun HY, Hanley FL, Olson I, Punn R. Coronary sinus obstruction after atrioventricular canal defect repair. Congenit Heart Dis 2014;9:E Gabrielle Vaughn, MD Vaughn GR, Moore JW, Mallula KK, Lamberti JJ, El-Said HG. Transcatheter stenting of the systemic-to-pulmonary artery shunt: A 7-year experience from a single tertiary center. Catheter Cardiovasc Interv 2015;86: Mallula K, Vaughn G, El-Said H, Lamberti JJ, Moore JW. Comparison of ductal stenting versus surgical shunts for palliation of patients with pulmonary atresia and intact ventricular septum. Catheter Cardiovasc Interv 2015;85: Matthew Williams, MD Williams MR, Shepard SM, Boramanand NK, Lamberti JJ, Perry JC. Long-term follow-up shows excellent transmural atrial lead performance in patients with complex congenital heart disease. Circ Arrhythm Electrophysiol 2014;7: Justin Yeh, MD May LJ, Montez-Rath ME, Yeh J, Axelrod DM, Chen S, Maeda K, Almond CS, Rosenthal DN, Hollander SA, Sutherland SM. Impact of ventricular assist device placement on longitudinal renal function in children with end-stage heart failure. J Heart Lung Transplant 2016;35: Gupta P, Rettiganti M, Gossett JM, Yeh JC, Jeffries HE, Rice TB, Wetzel RC. Risk factors for mechanical ventilation and reintubation after pediatric heart surgery. J Thorac Cardiovasc Surg 2016;151: May LJ, Ploutz M, Hollander SA, Reinhartz O, Almond CS, Chen S, Maeda K, Kaufman BD, Yeh J, Rosenthal DN. A novel pediatric treatment intensity score: development and feasibility in heart failure patients with ventricular assist devices. J Heart Lung Transplant 2015;34: Gupta P, Chow V, Gossett JM, Yeh JC, Roth SJ. Incidence, predictors, and outcomes of extubation failure in children after orthotopic heart transplantation: a single-center experience. Pediatr Cardiol 2015;36: May LJ, Yeh J, Maeda K, Tyan DB, Chen S, Kaufman BD, Bernstein D, Rosenthal DN, Hollander SA. HLA desensitization with bortezomib in a highly sensitized pediatric patient. Pediatr Transplant 2014;18:E Lal AK, Chen S, Maeda K, McCammond A, Rosenthal DN, Reinhartz O, Yeh J. Successful bridge to transplant with a continuous flow ventricular assist device in a single ventricle patient with an aortopulmonary shunt. ASAIO J 2014;60: Siehr SL, Bernstein D, Yeh J, Berry GJ, Rosenthal DN, Hollander SA. Orthotopic heart transplantation in two infants with histiocytoid cardiomyopathy and left ventricular non-compaction. Pediatr Transplant AWARDS & HONORS Christopher Davis, MD, PhD Elected Fellow of the American Heart Association, 2013 Kanishka Ratnayaka, MD Orloff Science Award (National Heart, Lung, and Blood Institute Division of Intramural Research) for Clinical Translation of MRI Heart Catheterization, 2013 National Heart, Lung, and Blood Institute Director s Award for Outstanding Research (Developing and Translating into Practice the Caval-Aortic Technique of Transcatheter Aortic Valve Replacement) 2013 National Heart, Lung, and Blood Institute Director s Award for Partnership/Collaboration (Launching the Pediatric Interventional Cardiac Magnetic Resonance Program, a Collaboration Between NHLBI and Children s National Medical Center) 2013 Children s National Medical Center Mentor Award, 2015 National Heart, Lung, and Blood Institute Director s Award for Outstanding Clinical Research Award For the Implementation of Radiation-Free, MRI-Guided Right Heart Catheterization in Pediatric Patients, UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 141

72 CARDIOTHORCIC SURGERY The Pediatric Cardiac Surgery Division of the Division of Cardiothoracic Surgery at the University of California, San Diego (UCSD) School of Medicine is based at Rady Children s Hospital-San Diego (RCHSD). The Division, in conjunction with the Division of Pediatric Cardiology, provides cardiovascular surgery services for infants, children and adults with congenital and acquired heart disease. The Division serves the San Diego metropolitan area (population: 3.2 million) and it is a major referral center for Imperial and Orange Counties, Hawaii, New Mexico, Mexico, and the Pacific Rim Islands. Dr. John J. Lamberti is the Joyce and Eugene Klein Director of the Heart Institute at RCHSD and he is Division Chief of Cardiovascular Surgery at RCHSD. Dr. Eric Devaney joined the division on April 1, Dr. Devaney is an Associate Professor of Surgery at UCSD and he is the Director of Cardiac Transplantation and Cardiac Assist Devices at RCHSD. After Dr. Peter Pastuszko, former Associate Clinical Professor of Surgery at UCSD, resigned in 2013, Dr. Devaney assumed the role of Medical Director of Pediatric Cardiac Surgery Critical Care at RCHSD. The Division s clinical volume for the academic years remained steady when compared to previous academic years. The complexity of the caseload has increased due to increasing referrals from outlying areas in Southern California and the State of Hawaii. RCHSD is a high volume pediatric cardiac surgical program according to the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database. The Division s outcomes are comparable with other leading high volume centers. The STS analysis is based upon risk-adjusted data. The complexity score for RCHSD is slightly higher than the national average reflecting our role as a major referral center. The Division of Cardiothoracic Surgery receives referrals from San Diego, Orange and Imperial counties; the Naval Medical Center, San Diego; the San Diego Regional Kaiser Medical Center; Tripler Army Medical Center, Honolulu, Hawaii; Kapiolani Medical Center for Women and Children, Honolulu, Hawaii; Straub Clinic, Honolulu, Hawaii and the Kaiser Permanente Medical Group, Honolulu, Hawaii. The Division s surgical volume for the fiscal The cardiac surgeons participate in the following teaching activities: Daily morning and afternoon rounds at RCHSD with cardiac surgery fellows, cardiology fellows, ICU fellows, nurses, nurse practitioners,nurses in training, medical students, pediatric residents and cardiology attendings Biweekly teaching rounds with the PICU team and monthly teaching conferences with the NICU team Conferences at RCHSD and UCSD Medical Centers including the transplantation conference, adult cardiology/cardiothoracic surgery conference, pediatric cardiology/cardiothoracic surgery conference and cardiothoracic surgery resident teaching conference Cardiothoracic surgery outpatient and the Transplant clinics at UCSD and RCHSD Medical student rotations in CT surgery and Clinical Anatomy. CLINICAL ACTIVITIES years was 1,391 cases. The faculty provides consultative services at UCSD Medical Center, RCHSD, Sharp Mary Birch Hospital and at all referral sites in Hawaii. In addition, faculty members provide varying levels of support for adult patients with congenital heart disease undergoing treatment at all of the adult hospitals in San Diego county. TEACHING ACTIVITIES Dr. Lamberti is the mentor, consultant and advisor to the congenital heart surgery program at Kapiolani Medical Center for Women and Children (KMCWC) in Honolulu, Hawaii. KMCWC is the primary pediatric teaching hospital of the John A. Burns School of Medicine Department at The University of Hawaii Manoa. Since 1994, Dr. Lamberti has spent five weeks each year at KMCWC assisting in surgery, participating in pre and postoperative care and overseeing quality assurance aspects of the cardiac surgery program. Dr. Lamberti makes teaching rounds every morning during Hawaii Heart Week. He also chairs the peer review committee meeting at KMCWC, and participates in the case review conferences. John Lamberti, MD The Division participates in multiple longitudinal studies of congenital heart disease sponsored by the Congenital Heart Surgeon s Society. Dr. John J. Lamberti is the principal investigator on multiple clinical protocols involving complex congenital heart defects. The studies are designed to evaluate the natural history, including before and after surgical therapy, of relatively rare congenital heart defects in a multi-center collaborative effort. Eric J. Devaney, MD Dr. Devaney has a strong interest in basic science, clinical research and cardiac transplantation. Dr. Devaney has been instrumental in the creation of a cardiovascular ICU (CVICU) at RCHSD. Dr. Devaney is responsible for the recruitment of personnel and the creation of the infrastructure that will permit RCHSD to begin cardiac transplantation in Dr. Devaney is a member of the RCHSD Research Council. RESEARCH SUPPORT John Lamberti, MD STARFlex in Atrial Septal Defect- Long term Status Assessment of Patients Aug Indefinite $2,900 "Following Closure of ASD with the STARFlex Septal Occlusion System in IDE Study" G (SALSA)/NMT MEDICAL, INC. Sept Indefinite $198,865 Johns Hopkins University "Coarctation of the Aorta Trail (COAST)" Closure of Muscular Ventricular Septal Defects with the Amplatzer Muscular VSD $26,600 Occluder-Post Approval Study (Muscular VPA) Sept Indefinite AGA Medical Corporation Eric Devaney, MD K08 HL : $620,000 NIH K08 Mentored Scientist Award "Genetic Modification of Cardiac Motor Proteins in Normal and Failing Myocytes" Surgical Research Grant $50,000 Rady Children s Hospital, San Diego "Pluripotent Stem Cells from Human Thymus" PUBLICATIONS DiBardino DJ, Gomez-Arostegui J, Kemp A, Raviendran R, Hegde S, Devaney EJ, Lamberti JJ, El-Said H. Intermediate Results of Hybrid Versus Primary Norwood Operation. Ann Thorac Surg Jun;99(6):2141-7; discussion doi: /j. athoracsur Epub 2015 Apr 15. PubMed PMID: Vaughn GR, Moore JW, Mallula KK, Lamberti JJ, El-Said HG. Transcatheter stenting of the systemic-to-pulmonary artery shunt: A 7-year experience from a single tertiary center. Catheter Cardiovasc Interv Sep;86(3): doi: /ccd Epub 2015 Apr 2. PubMed PMID: Mallula K, Vaughn G, El-Said H, Lamberti JJ, Moore JW. Comparison of ductal stenting versus surgical shunts for palliation of patients with pulmonary atresia and intact ventricular septum. Catheter Cardiovasc Interv Jun;85(7): doi: / ccd Epub 2015 Feb 23. PubMed PMID: RESEARCH ACTIVITIES DiBardino DJ, Hegde S, Lamberti JJ. Further insight into a rare pathology: differential aspects of left ventricular diverticulum. World J Pediatr Congenit Heart Surg Oct;5(4): doi: / PubMed PMID: Williams MR, Shepard SM, Boramanand NK, Lamberti JJ, Perry JC. Long-term follow-up shows excellent transmural atrial lead performance in patients with complex congenital heart disease. Circ Arrhythm Electrophysiol Aug;7(4): doi: / CIRCEP Epub 2014 Jun 6. PubMed PMID: DiBardino DJ, Gomez-Arostegui J, Kemp A, Raviendran R, Hegde S, Devaney EJ, Lamberti JJ, El-Said H. Intermediate Results of Hybrid Versus Primary Norwood Operation. Ann Thorac Surg Jun; 99(6): PMID: Law W, DiBardino DJ, Raviendren R, Devaney E, Davis C. Anomalous aortic origin of the left coronary artery: in-hospital cardiac arrest and death despite bed rest. World J Pediatr Congenit Heart Surg Oct; 5(4): PMID: Bizy A, Guerrero-Serna G, Hu B, Ponce-Balbuena D, Willis BC, Zarzoso M, Ramirez RJ, Sener MF, Mundada LV, Klos M, Devaney EJ, Vikstrom KL, Herron TJ, Jalife J. Myosin light chain 2-based selection of human ipsc-derived early ventricular cardiac myocytes. Stem Cell Res Nov; 11(3): PMID: Iyengar A, Scipione CN, Sheth P, Ohye RG, Riegger L, Bove EL, Devaney EJ, Hirsch-Romano JC. Association of complications with blood transfusions in pediatric cardiac surgery patients. Ann Thorac Surg Sep; 96(3): PMID: AWARDS & HONORS John Lamberti, MD , Castle Connolly, America s Top Doctors Eric J. Devaney, MD Lead Surgeon, Annual Relief Mission, Arturo Grullon Children s Hospital, Santiago, Dominican Republic and Bloom Hospital, San Salvador, El Salvador 142 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 143

73 Hematology/ Oncology 144 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 145

74 INTRODUCTION The Division of Hematology/Oncology provides state-of-the-art care in the Peckham Center for Cancer and Blood Disorders. The Division serves patients in all of San Diego and Imperial counties, and in Southwest Riverside County. FACULTY Through the UC San Diego Moores Cancer Center, the Division is part of a National Cancer Institute designated Comprehensive Cancer Center. The Division of Pediatric Hematology/Oncology is also devoted to basic, translational, and clinical research, experimental therapeutics, and medical education. The Division has the following programs: Stem Cell Transplantation Program and Comprehensive Clinic Sickle Cell Disease Program and Comprehensive Clinic Hemophilia Program and Comprehensive Clinic Neuro-Oncology Program and Comprehensive Clinic Long-Term Follow-Up Program and Comprehensive Clinic Palliative/Supportive Care Program, funded by a grant from the Peckham Family Foundation Integrative Medicine Program Comprehensive Psychosocial Services Program, funded in part by the Celebration of Champions through the Rady Children s Hospital Auxiliary In July 2007, an alliance was formed between St. Jude Children s Research Hospital, RCHSD and UCSD. The alliance focuses on the development of clinical, translational, and basic research in the area of childhood cancer. Several joint clinical trials are available to the children in San Diego. Also, joint efforts in international outreach have led to the creation of successful Pediatric Oncology Programs in Tijuana and La Paz, Mexico. William D. Roberts, MD Division Chief & Clinical Professor Hyunah Ahn, MD Associate Clinical Professor Eric J. Anderson, MD Associate Clinical Professor M. Paula Aristizabal, MD, MS Assistant Professor Sun Choo, MD Assistant Professor Division faculty are actively involved in teaching through the UCSD/RCHSD Pediatric Residency Program and the UCSD School of Medicine. The division has a Pediatric Hematology/Oncology Fellowship Program accredited by the ACGME, which accepts two new fellows per year in to the three-year program. Affiliated with St. Jude Children s Research Hospital for nearly a decade DIVISION FAST FACTS Over 14,000 outpatient visits per year John R. Crawford, MD Associate Professor & Neurosciences, Director, Neuro-Oncology Program, Director, Child Neurology Residency Program Mitchell B. Diccianni, PhD Associate Project Scientist Donald L. Durden, MD, PhD Professor Jenny M. Kim, MD Associate Clinical Professor Amy E. Geddis, MD Associate Clinical Professor MAJOR PLANS AND GOALS Leveraging the resources of the newly created Rady Genomic Institute, we will comprehensively sequence all newly diagnosed and relapsed/refractory brain tumors at RCHSD, and collect a diverse array of information about each patient s tumor to guide therapy. At the time of surgery, each patient s tumor will be profiled to characterize mrna and non-coding RNA expression, DNA mutations and copy number changes, and DNA methylation. Cells from each tumor will be subjected to high-throughput drug screening to provide empirical evidence for therapies that may be effective. Tumor tissue will be orthotopically transplanted into mice to create xenografts that can serve as tools for further drug discovery and preclinical testing. Each patient s genomic and drug response data will be reviewed by a molecular tumor board consisting of physicians and scientists, and the most promising therapies will be prioritized for clinical use. Every patient will be enrolled in an n-of-1 clinical trial, and ideally, each patient will receive the most appropriate therapy for his or her tumor. Planning for the expansion of the Early Phase Oncology Clinical Trials Program is underway. This will allow us to offer a wider variety of therapeutic clinical trials to all relapsed and refractory oncology patients. Drug development in laboratories at UCSD is providing the opportunity to study promising agents that have the potential to offer increased efficacy and decreased side-effects. A Clinical Care Re-Design task force is planned, which will closely examine all aspects of the patient experience at the Peckham Center for Cancer & Blood Disorders, including the inpatient unit and clinic. We will ensure the efficiency and efficacy of the diagnostic and therapeutic interventions for our patients, including medical and psychosocial care. Dennis Kuo, MD Associate Clinical Professor Janet Yoon, MD Associate Clinical Professor Faith H. Kung, MD Associate Professor Alice L. Yu, MD, PhD Professor Deborah E. Schiff, MD Clinical Professor Jennifer Yu, MD Assistant Professor Courtney Thornburg, MD, MS Associate Professor of Clinical Pediatrics Jing Yang, PhD Associate Professor & Pharmacology FELLOWS Preethi Ganesan, MD Nicholas Gloude, MD Ksenya Shliakhtsitsava, MD Tina Udaka, MD William Woolbright, MD Victor Wong, MD 146 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 147

75 The clinical program is housed in the RCHSD Acute Care Pavilion, occupying the entire second floor with a 38-bed inpatient unit, which includes a 10-bed BMT unit, and an outpatient clinic containing an infusion center, procedure room, and exam rooms. The Center also includes a pharmacy, schoolroom, activity room, adolescent lounge, and conference rooms. The clinical team is made up of hematology/oncology physicians, nurse practitioners, nurses, pharmacists, psychologists, social workers, child life specialists, parent liaisons, dieticians, and translators. There are over 14,000 outpatient visits per year and an average daily inpatient census of 35 patients. Approximately 250 new oncology patients are diagnosed per year, 125 patients are seen per year in the Sickle Cell Disease/Hemoglobinopathy program, and over 400 patients are seen in the Hemophilia/Bleeding Disorder/ Thrombosis program. Approximately 30 related and unrelated hematopoietic stem cell transplants (HSCT) are performed each year. The program is a National Marrow Donor Program (NMDP) Unrelated Donor Transplant Center, and has achieved accreditation by the Foundation for Accreditation of Cellular Therapeutics (FACT). The HSCT program is a joint program with the adult HSCT program at UCSD, and includes combined endeavors in clinical care, quality, outcomes, and research. We provide pediatric oncology care to patients treated at the Rady Children s Proton Therapy Program, in partnership with Scripps Health. CLINICAL ACTIVITIES All faculty members are actively involved in teaching activities for the hematology/oncology fellows, residents in the UCSD/RCHSD Pediatric Residency Program, other residents and fellows working at RCHSD, and UCSD medical students. Clinical teaching occurs in the inpatient and outpatient settings. The faculty provides formal lectures to the residents and students, attend morning report, morbidity & mortality conferences, and other teaching conferences. Eric Anderson, MD is an advisor for fellows in the Hematology/ Oncology Fellowship Program. Sun Choo, MD is an Associate Director of the Hematology/Oncology Education and Training Programs and an advisor for fellows in the Hematology/Oncology Fellowship Program. John R. Crawford, MD is an advisor for fellows in the Hematology/ Oncology Fellowship Program. Jenny M. Kim, MD is an advisor for fellows in the Hematology/ Oncology Fellowship Program. She is a CPC Preceptor for UCSD/ RCHSD pediatric residents. Hyunah E. Ahn, MD is the Director of Hematology/Oncology Inpatient Services. Eric J. Anderson, MD is the Director of the Stem Cell Transplantation Program and the Director of Hematology/Oncology Outpatient and Infusion Services. Paula Aristizabal, MD, MS is the Director of the International Hematology/Oncology Program. She conducts research addressing issues related health literacy and cancer disparities. She is the coordinator for the Pediatric Oncology twinning programs in Tijuana and La Paz, Mexico. Sun Choo, MD is an Associate Director of the Hematology/Oncology Education and Training Programs. She is a member of the Yang Lab, studying the molecular basis of metastasis in the Ewing Sarcoma Family of Tumors. Her work demonstrating that up-regulation 148 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report The Division also manages the following programs: TEACHING ACTIVITIES RESEARCH ACTIVITIES Neuro-Oncology, a multidisciplinary team involved in the care of patients with central nervous system malignancies. This includes a specific Neuro-Oncology Tumor Board. Long Term Follow-up, which monitors survivors of childhood cancer who are more than two years from the completion of therapy, and which provides a wide range of services through a multidisciplinary team focused on issues related to survivorship. Palliative Care, which offers assistance with medical decisionmaking, clinical care coordination, and family support for patients and their families undergoing intensive therapy and/or facing difficult decisions. Integrative Medicine, which offers support for patients through interventions such as biofeedback, acupuncture, and nutrition counseling. A Pain Management Program, managed by the Anesthesiology Department, works closely with the hematology/oncology patients providing pain control therapy and sedation for patients undergoing procedures, such as bone marrow aspiration/biopsy and lumbar puncture. Dennis Kuo, MD is the Program Director for the Hematology/ Oncology Fellowship Program. Deborah E. Schiff, MD serves as a faculty preceptor and advisor for UCSD medical and pharmacy student independent study projects. She is an advisor for fellows in the Hematology/Oncology Fellowship Program and a member of the Fellowship Scholarship Oversight Committee. Courtney Thornburg, MD is an advisor for fellows in the Hematology/Oncology Fellowship Program and a member of the Fellowship Scholarship Oversight Committee. Janet Yoon, MD is an advisor for fellows in the Hematology/ Oncology Fellowship Program Jennifer Yu, MD is an Associate Director of the Hematology/ Oncology Education and Training Programs, and an advisor for fellows in the Hematology/Oncology Fellowship Program. of Twist1 and its targets, such as PDGFR alpha, correlates with metastatic disease and poor outcome has led to studies to determine if targeting the associated pathways may inhibit metastases and improve prognosis. John R. Crawford, MD, MS is the Director of the Neuro-Oncology Program. He is the RCHSD/UC San Diego site PI for the Pacific Pediatric Neuro-Oncology Consortium (PNOC). He is a Co- Investigator for the following clinical trials: SJM12 A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma, PNOC 001 Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children, PNOC003 Molecular Profiling for Individualized Treatment Plan for DIPG, SJATRT Phase 2 study of alisertib as a single agent in recurrent and refractory central nervous system atypical teratoid rhabdoid tumors (ATRT) and extra CNS malignant rhabdoid tumors (MRT) and in combination therapy in newly diagnosed ATRT, and PolyICLC in Pediatric Low Grade Glioma: A UCSD Phase 2 Trial. Donald L. Durden, MD, PhD developed and executed the Rady/ UCSD Biorepository for the collection of pediatric tissue for research for all Divisions within the Department, and serves the Director of the Biorepository. Dr. Durden is the Director of Basic and Translational Research in the Division. He is Associate Director for Pediatric Oncology at the Moores UCSD Cancer Center (MCC). He is the PI on a multicenter Phase II trial of a biologic response modifier, polyiclc in low grade glioma brain tumors in collaboration with Dr. Crawford. He developed one of the first PI-3 kinase inhibitors to go into human clinical trials. This drug, SF1126, is slated for a pediatric oncology clinical trial in The Durden laboratory is interested in understanding the mechanisms by which signals are transmitted from cell surface receptors to the cytoplasm and nucleus. The efforts are focused on the role of lipid and protein phosphorylation and dephosphorylation in the regulation of signal transduction. They study the regulation of signal transduction pathways in tumor cells as well as similar signaling events in myeloid and endothelial cells as they relate to the control of the tumor microenvironment. They aim to understand how the phosphorylation and dephosphorylation of cellular proteins and lipids results in regulated and coordinated signal relay and how components of other signaling pathways (e.g. PI-3 kinase, small G proteins, phosphatases, serine/threonine kinases, PLC, GAPs, protein kinase A, PKC, etc.) interact to fine tune and regulate cell signaling in the context of other environmental influences or when different receptors are activated at the same time. They are interested in converting target discovery and validation into drug discovery and drug development in particular as it relates to specific kinases and phosphatases, and translating this basic science information from bench to bedside. His group is actively involved in drug discovery and development and in opening Phase I and Phase II clinical trials of novel targeted therapeutic agents in pediatric oncology. Jenny M. Kim, MD is the Director of the RCHSD Comprehensive Sickle Cell Disease and Hemoglobinopathy program. Dennis Kuo, MD is the Director of the Long Term Follow-up Program for Cancer Survivors and the Hematology/Oncology Fellowship Program Director. William D. Roberts, MD is the Division Chief for Hematology/ Oncology. He is a founding member of the Neuroblastoma & Medulloblastoma Translational Research Consortium (NMTRC) and the RCHSD/UC San Diego site PI. He is a co-investigator for the following NMTRC clinical trials: NMTRC003: A Phase II Preventative Trial of DFMO as a Single Agent in Patients with High Risk Neuroblastoma in Remission, NMTRC 009- Molecularguided therapy for the treatment of patients with relapsed and refractory childhood cancers, NMTRC 011- A Phase I Trial of Tolcapone alone and in Combination with Oxaliplatin in Patients with Relapsed or Refractory Neuroblastoma or Medulloblastoma, NMTRC012 A Pilot Study Using Molecular Guided Therapy with Induction Chemotherapy followed by maintenance with DFMO for Subjects with Newly Diagnosed High-Risk Neuroblastoma. Along with Drs. Paula Arisitzabal, and Raul Ribeiro, he participated in the development of the joint RCHSD/UCSD/St. Jude Children s Research Hospital Pediatric Oncology International Outreach Programs in Tijuana and La Paz, Mexico. Deborah E. Schiff, MD is the Medical Director of the Hematology/ Oncology Palliative Care Program and the Physician Coordinator of the RCHSD/UCSD/St. Jude Children s Research Hospital Alliance. She has served as the RCHSD/UCSD principal investigator for 12 St. Jude clinical trials, including: AML08 A Phase III Randomized Trial of Clofarabine Plus Cytarabine Versus Conventional Induction Therapy and a Phase II Study of Natural Killer Cell Transplantation in Patients with Newly Diagnosed Acute Myeloid Leukemia, SJBC3 Mature B-cell Lymphoma and Leukemia Study III, NHL16 Study for Newly Diagnosed Patients with Acute Lymphoblastic Lymphoma, and HOD08 Combination Chemotherapy with or without Radiation Therapy in Treating Young Patients with Favorable-Risk Hodgkin Lymphoma. Courtney Thornburg, MD, MS is the Director of the Hemophilia/ Bleeding Disorder program. She has held a leadership role in several multi-center studies of the role of hydroxyurea in the management of sickle cell disease. She was the first author on a publication in Pediatric Blood and Cancer describing medication and visit adherence, the first author on a publication in Blood describing clinical eventsand a co-author on other related manuscripts, including the primary paper which was published in Lancet. She has also been involved in multi-center studies of stroke prevention, pain management, quality of life, and neurocognitive outcomes. She is the principal investigator for the RCHSD/HTC Universal Data Collection Study and the HTRS Registry for public health surveillance of individuals with bleeding disorders. She is participating in the Kids DOTT trial to better determine the optimal duration of anticoagulation therapy in pediatric thrombosis patients. Jing Yang, PhD conducts basic science research related to metastases in cancer and Twist mutations in metastatic cancers. She is involved in the study of the molecular basis of metastasis in the Ewing Sarcoma Family of Tumors with Dr. Sun Choo. She was awarded a 2007 NIH Director s New Innovator Award to develop a novel Epithelial-Mesenchymal Transition in Tumor Metastasis detection/ selection system in mice to identify, image and isolate migrating carcinoma cells in primary tumors and to explore the signal pathways that promote carcinoma cells to migrate and disseminate into distant organs. Janet Yoon, MD is the RCHSD/UCSD principal investigator for Phase II Study of everolimus for recurrent or progressive low-grade gliomas in children, conducted through the Pacific Pediatric Neuro- Oncology Consortium. Alice Yu, MD, PhD is pursuing translational cancer research. She chairs a multi-national Phase III trial of anti-gd2 in highrisk neuroblastoma, which was the pivotal trial for licensing of this antibody by the FDA. In addition, Dr. Yu directs a research laboratory, which includes Drs. Diccianni and Batova. Their research focuses on the role of immune effector cells in immunotherapy of cancer, the role of micro-rna in leukemia, and novel therapy of cancer targeting molecular abnormalities associated with chromosome 9p21, which is frequently altered in many types of cancer. Jennifer Yu, MD is the Associate Director of the Sickle Cell Disease and Hemoglobinopathy Program and an Associate Director of the Hematology/Oncology Education and Training Programs. RESEARCH SUPPORT Eric J. Anderson, MD Local PI: HRPP # Information Sharing Program for Blood and Marrow Transplant Procedures (and Contribution of Blood Sample to NMDP Research Sample Repository) Local PI: HRPP # A Multicenter Access And Distribution Protocol For Unlicensed Cryopreserved Cord Blood Units (Cbus) For Transplantation In Pediatric And Adult Patients With Hematologic Malignancies And Other Indications (Protocol 10 CBA) Local PI: HRPP # NCT , A Multicenter Safety Study of Unlicensed, Investigational Cryopreserved Cord Blood Units (CBUs) Manufactured by the National Cord Blood Program (NCBP) and Provided for Unrelated Hematopoietic Stem Cell Transplantation of Pediatric and Adult Patients (Protocol ) Local PI: HRPP # Defibrotide for Patients with Hepatic Veno-Occlusive Disease (VOD): A Treatment IND Study Local PI: HRPP # : A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 149

76 Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime with Campath-1H, Fludarabine and Melphalan Local PI: HRPP # (Closed to accrual) BMT-CTN-0501-Multi-Center, Open Label, Randomized Trial Comparing Single Versus Double Umbilical Cord Blood (Ucb) Transplantation In Pediatric Patients With High Risk Leukemia and Myelodysplasia Paula Aristizabal, MD, MS (PI) 5/2013-present $65,000 International Community Foundation "Establishing a Twinning program in pediatric oncology in Baja California Sur" (Co- PI) 1/2009-1/2016 $440,0 00 Sanofi-Espoir Foundation "Establishing a surveillance system in pediatric oncology in Colombia" (Co- PI) 11/2008-ongoing $220,000 St. Jude Children s Research Hospital-Rady Children s Hospital Joint International Outreach Program "Establishing a Twinning program in pediatric oncology in Baja California, Mexico" (PI) 11/ /2015 $30,000 American Cancer Society- Institutional Research Grant "Outcomes of informed consent in pediatric oncology: A feasibility pilot study" Racial/ethnic disparities in pediatric oncology clinical trial enrollment at Rady Children s Hospital (PI of associated research) 11/2012-6/ ,000 National Cancer Institute Diversity Supplement to the Specialized Cancer Center Support Grant (PI) 6/2015-9/2015 $5,000 NIH Short Term Research Training Grant Vitamin D deficiency in pediatric cancer patients: Supplementation and clinical outcomes in newly diagnosed patients and survivors. (PI) 6/2014-9/2014 $5,000 National Institutes of Health Short Term Research Training Grant Implementation of a Twinning Program in Pediatric Oncology at the U.S-Mexican border. Sun Choo, MD National Institutes of Health Loan Repayment Program $35,000/year loan repayment July Current July 2014 Current $50,000 Rady Children s Intramural Research Grant Research Funding for Developing a Novel Therapeutic Approach for Ewing s Sarcoma Metastasis project July 2013 Current $123,149 St. Baldrick s Fellow Grant Research Funding for Developing a Novel Therapeutic Approach for Ewing s Sarcoma Metastasis project Donald L. Durden, MD, PhD RO1 FD A2 (PI) 7/01/14-6/31/2018 $258,000 Phase II trial of poly-iclc in pediatric low grade glioma (CO-I (with NANT consortium)) 7/01/14-6/31/18 $270,000 St. Baldrick s Foundation Grant Funding for Phase I trial of SF1126 (First PI-3K inhibitor in pediatric oncology) T (Faculty mentor and Co-I; Howell PI) T32 and K12 UCSD Training Grant in Drug Development (PI) 10/01/13-9/01/15 $125,000 Hyundai Hope Grant R21CA A1 (PI) 7/01/2013-6/30/2015 $250,000 NIH Nanoparticle enabled L-asparaginase therapy for CLL (PI) 5/01/2013-4/31/2015 $50,000 UCSD Department Genomics Grant Genomics of Sickle Cell Disease R21CA A1 (Co-I) 7/01/2013-6/30/2015 $250,000 Nanoparticle enabled L-asparaginase therapy for CLL Cricket Corporation, Inc. 05/ /2015 $75,000 Poly-ICLC in Management of Recurrent Low Grade Gliomas (Phase II). Donald L. Durden, M.D., Ph.D., Principal Investigator (multicenter trial)(biology study: TLR3 stimulation of innate and adaptive immune response against the tumor is the mechanism for polyic antitumor activity). This is a form of immunotherapy under study in the Durden laboratory (open to enrollment, Clintrials.gov: NCT ). RO1 FDA FD grant funded 2014, $1.6M, (IRB ). 11 patients enrolled, 50% response rate so far. Vascular targeted pan PI-3 kinase bromodomain inhibitor, SF1126, for neuroblastoma therapeutics. First in pediatrics Phase I trial in pediatric solid tumor. NANT Phase I trial. Approved. Durden, inventor and developer of this agent. (opened for enrollment 8/2015). F1126&rank=2 Jenny Kim, MD EXJADE (Deferasirox, ICL670) (PI) Novartis A 3-year, Prospective, Non-Interventional Multicenter Registry in Sickle Cell Disease Patients (PI) 2011 Present $10,000 UCSD Clinical and Translational Research Institute Biomarkers of Human Sickle Cell Disease (Co-I) 2014 Present ADVENTRX Pharmaceuticals/Mast Therapeutics Inc. Evaluation of purified poloxamer 188 in vaso-occlusive crisis of sickle cell disease (EPIC) Dennis Kuo, MD (PI) 10/ /2014 $75,000 Hyundai Hope on Wheels 150 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 151

77 William D. Roberts, M.D U10 CA (PI) 03/ /2016 $44,257 NIH (Children s Oncology Group (COG) Multi-Institution Clinical Trials Group (Adamson) (#19630)) (PI) 2015 $50,000 St. Baldrick s Foundation Infrastructure Award 9/2012 9/2014 $250,000 (Jing Yang, PhD and William Roberts, MD, Co-PIs) Hyundai Hope on Wheels Dissecting the Molecular Basis of Ewing s Sarcoma Metastasis 5R01ES (UCSD PI) 08/01/ /31/2013 $72,000 NIH (NIEHS) Environmental and Molecular Epidemiology of Childhood Leukemia (PI) 2013 $50,000 St. Baldrick s Foundation NMTRC 009 (Study Member/UCSD PI) 2014 Present Molecular-guided therapy for the treatment of patients with relapsed and refractory childhood cancers NMTRC 008 (Study Member/UCSD PI) A Feasibility Trial using Molecular-Guided Therapy for the Treatment of Patients with Relapsed and Refractory Childhood Cancer NMTRC 003 (Study Member/UCSD PI) 2012 Present A Phase II Preventative Trial of DFMO as a Single Agent in Patients with High Risk Neuroblastoma in Remission William D. Roberts, M.D NMTRC 005 (Study Member/UCSD PI) A Randomized, Phase I/II trial of Irinotecan and Temozolomide compared to Irinotecan and Temozolomide in Combination with TPI 287 in Patients with Primary Refractory or Early Relapsed Neuroblastoma William D. Roberts, M.D NMTRC 004 (Study Member/UCSD PI) A Phase I/II Trial of TPI 287 in Patients with Refractory or Recurrent Neuroblastoma and Medulloblastoma Deborah Schiff, MD SJ AML08 (RCHSD PI) 11/ Present A Phase III Randomized Trial of Clofarabine plus Cytarabine versus Conventional Induction Therapy for Patients with Newly Diagnosed AML SJBC3 (RCHSD PI) 2012 Present Mature B-Cell Lymphoma and Leukemia Study III SJ NHL16 (RCHSD PI) 2014 Present NHL16 Study for Newly Diagnosed Patients with Acute Lymphoblastic Lymphoma SJ HOD08 (RCHSD PI) 2014 Present Combination Chemotherapy with or without Radiation Therapy in Treating Young Patients with Favorable-Risk Hodgkin Lymphoma SJ HOD05 (RCHSD PI) Chemotherapy with Low-Dose Radiation for Pediatric Hodgkin Lymphoma SJ MEL06 (RCHSD PI) Phase II Study Incorporating Pegylated Interferon in the Treatment for Children with High-Risk Melanoma Jing Yang, PhD #RSG CSM (PI: Yang) 01/01/ /31/2015 American Cancer Society In vivo activation of Twist in breast cancer metastasis 1R01CA (PI: Yang) 09/01/ /30/2017 NIH (NCI) Regulation of Tumor Invasion by Twist1 W81XWH (PI: Yang, Partnering-PI: Engler 06/01/ /31/2016 DOD Regulation of breast cancer stem cells by Tissue Rigidity 1 R21 CA (PI: Yang) 12/01/ /30/2016 NIH (NCI) Dissecting molecular determinants of carcinoma dormancy in vivo (PI 05/01/ /30/2015 The Hartwell Foundation Targeting Neural Crest Migration Program to Treat Ewing s Sarcoma Metastasis (PI) 09/01/ /01/2014 Hyundai Hope on Wheels Foundation Developing a Novel Therapeutic Approach for Ewing s Sarcoma Metastasis Janet Yoon, MD (Co-PI) 07/2013 Present Pacific Pediatric Neuro-Oncology Consortium, University of California San Diego, Rady Children s Hospital PNOC 001(PI) 2014 Current Phase II study of Everolimus for recurrent or progressive low-grade gliomas in children Jennifer Yu, MD (Co-I) 2012 Present Biomarkers in Human Sickle Cell Disease, Clinical Trial (Site Co-PI) 2015 Present Cooperative Agreement for Comprehensive Medical Care for Thalassemia, HRSA (Site Co-PI) Present Outcomes in AML, inpatient vs outpatient care during neutropenia, PCORI (Co-I) 2015 Present KID.DOTT Duration of anticoagulation Trial, Clinical Trial (Co-I) 2015 Present Oral Rivaroxaban Trial in Pediatrics, Clinical Trial (Co-I) Present MST Trial Poloxamer for VOC in Sickle Cell Disease, Clinical Trial PUBLICATIONS M. Paula Aristizabal, MD Torres D, González ML, Loera A, Aguilera M, Relyea G, Aristizabal P, Caniza MA. The Centers for Disease Control and Prevention definition of mucosal barrier injury-associated bloodstream infection improves accurate detection of preventable bacteremia rates at a pediatric cancer center in a low- to middle-income country. Am J Infect Control. doi: /j.ajic PMID: Aristizabal P, Fuller S, Rivera R, Beyda D, Ribeiro RC, Roberts W. Improving Pediatric Cancer Care Disparities Across the United States-Mexico Border: Lessons Learned from a Transcultural Partnership between San Diego and Tijuana. Front Public Health Jun 22;3:159. Chen DY, Aristizabal P, Crawford JR. Preoperative Presentation of a Variant of Cerebellar Mutism Syndrome in a Young Boy With Juvenile Pilocytic Astrocytoma. Pediatr Neurol Sep;53(3): Bravo LE, García LS, Collazos P, Aristizabal P, Ramirez O. Descriptive epidemiology of childhood cancer in Cali: Colombia Colomb Med (Cali) Sep 30;44(3): John Crawford, MD Crawford JR Childhood Brain Tumors Pediatr Rev Feb;34(2): Udaka YT, Yeh-Nayre LA, Amene CS, VandenBerg SR, Levy ML, Crawford JR. Recurrent Pediatric Central Nervous System Low-Grade Gliomas: The Role of Surveillance Neuroimaging in Asymptomatic Children. J Neurosurg Pediatr 2013;11: Gold JJ and Crawford JR. Acute Hemiparesis in a Child as a Presenting Symptom of Hemispheric Cerebral Proliferative Angiopathy. Case Rep Neurol Med 2013;2013: Ravikumar S Crawford JR. Role of Carbamazepine in the Symptomatic Treatment of Subacute Sclerosing Panencephalitis: Case Report and Review of the Literature. Case Rep Neurol Med 2013;2013: Dy M, Leshner RL, Crawford JR. An Unusual Case of Recurrent Guillain Barre Syndrome of a Different Subtype Five Years Post Initial Presentation. Case Rep Neurol Med. 2013: Gonda DD, Meltzer HS, Crawford JR, Hilfiker ML, Shellington DK, Peterson BM, Levy ML. Complications associated with prolonged hypertonic saline therapy in children with elevated intracranial pressure. Pediatr Crit Care Med. 2013;14: Udaka T, Shayan K, Yeh-Nayre L, Levy M, Chuang N Crawford JR Atypical Presentation of Atypical Teratoid Rhabdoid Tumor in a Child. Case Rep Oncol Med. 2013: Crawford JR, Shayan K, Levy ML. Delayed Presentation of Diencephalic Syndrome in a Child. BMJ Case Rep Jun 16;2013. doi:pii: bcr Crawford JR, Newbury RO, Levy ML. An Unusual Posterior Fossa Tumor in a Young Child. BMJ Case Reports Jun 26;2013. doi:pii: bcr Crawford, JR and Friedman, J. An Unusual Presentation of Posterior Fossa Ependymoma in a Child Neurology. BMJ Case Rep Jul 5;2013. doi:pii: bcr Jankowski P, Levy ML, Crawford JR. Post Traumatic Basal Ganglia Haemorrhage in Child with Primary Central Nervous System Lymphoma BMJ Case Rep Jul 31;2013. doi:pii: bcr Ceponene R, Levy ML, Crawford JR. Lobar haemorrhagic mass in a young girl with neurofibromatosis type 1. BMJ Case Rep Aug 23;2013. doi:pii: bcr Patel R, Levy ML, Crawford JR. Spontaneous Subdural Haemorrhage in a Child with Middle Cranial Fossa Arachnoid Cyst. BMJ Case Rep Aug 28;2013. doi:pii: bcr Gabel B, Newbury RO, Levy ML, Crawford JR. Giant Cerebellopontine Angle Schwannoma in a Child. BMJ Case Rep Sep 10;2013. doi:pii: bcr Jankowski P, Malicki DM, Levy ML, Crawford JR. Giant Intracranial Calcification Associated with New Onset Focal Seizure. Sep 7;2013 Gabel B, Yoon J, Levy ML, Crawford JR. Ring Enhancing Pontine Lesion in a Young Boy. BMJ Case Rep Sep 10;2013. doi:pii: bcr Gabel B, Yoon J, Levy ML, Crawford JR. A Rare Case of a Diffuse Intrinsic Pontine Glioma in a Neonate Diagnosed by Magnetic Resonance Imaging. BMJ Case Rep Jan 21;2014 Markant SL, Esparza LA, Sun J, Barton KL, McCoig LM, Grant GA, Crawford JR, Levy ML, Northcott PA, Shih D, Remke M, Taylor MD, Wechsler Reya RJ. Targeting Sonic Hedgehog-associated medulloblastoma through inhibition of Aurora and Polo-Like Kinases. Cancer Res. 2013;15: Hartman LL, Crawford JR, Makale MT, Milburn M Shweta J, Salazar AM Hasenauer B Vandenberg SR, MacDonald TJ, Durden DL. Phase II Trials of Poly-ICLC in the Management of Newly Diagnosed and Recurrent Pediatric Brain Tumors. J Pediatr Hematol Oncol Dec 4. Rismanchi N, Crawford JR. Bilateral Internuclear Ophthalmoplegia associated with Pediatric High Grade Glioma Progression: A Case Series and Review of the Literature. J Neuroonc. 2013;115: NA Chuang, JM Yoon, RO Newbury, Crawford JR. Glioblastoma Multiforme Arising from Dysembroplastic Neuroepithelial Tumor in a Child in the Absence of Therapy. J Pediatr Hematol Oncol Dec 4 (was C.2.) Gold, Crawford JR, Glaser C, Sheriff H, Wang S and Nespeca N. The role of continuous EEG in childhood encephalitis. Ped Neurol. 2014;50: Kool M, Jones DT, Jager N, Northcott AP, Pugh TJ, Hovestadt V, Piro RM, Adriana Esparza LA, Markant SL, Remke M, Milde T, Vourdeaut F, Ryzhova M, Sturm D, Pfaff E, Stark S, Hutter S, Seker- Cin H, Johann P, Bender S, Schmidt C, Rausch T, Shih D, Reimand J, Sieber L, Wittmann A, Linke L, Witt H, Weber JD, Zapatka M, Konig R, Beroukhim R, Bergthold G, van Sluis P, Volckmann R, Koster J, Versteeg R, Schmidt S, Wolf S, Lawrenz C, Bartholomae CC, van Kalle C, Unterberg A, Herold-Mende C, Hofer S, Kulozik AE, von Deimling A, Scheurlen W, Felsberg J, Reifenberger F, Hasselblatt M, Crawford JR, Grant GA, Jabado N, Perry A, Cowdrey C, Croul S, Zadeh G, Korbel JO, Doz F, Delattre O, Bader GD, McCabe MG, Collins VP, Kieran MW, Cho Y-J, Pomeroy SL, Witt O, Brors B, Taylor MD, Schuller U, Korschunov A, Eils R, Wechesler- Reya R, Lichter P, Pfister SM on behalf of the ICGC PedBrain Tumor Project. Genome Sequencing of SHH Medulloblastoma Predicts 152 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 153

78 Age-Dependent Response to Smoothened-Inhibition Cancer Cell. 2014;25:: Gabel B, Yoon J, Crawford JR. Clinical Isolated Syndrome Mimicking Focal Brainstem Glioma in a Child. BMJ Case Rep Mar 10; Nomura N, Pastorino S, Gymnopoulos M, Pengfe J, Lambert G, Crawford JR, Piccioni D, Juarez T, Pingle SC, Makale M, Kesari S. Prostate specific membrane antigen expression in primary gliomas and breast cancer brain metastasis. Cancer Cell Int :26. doi: / Qaddoumi I, Kocak M, Atmaram SP, Armstrong GT, Wetmore C, Crawford JR, Lin T, Boyett JM, Kun LE, Boop FA, Merchant TE, Ellison DW, Gajjar A, Broniscer A. Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High- Grade Gliomas. Front Oncol Apr 1;4:67 Wong V, Crawford JR. Extensive Subdural Spinal Enhancement Mimicking Leptomeningeal Disease in a Young Child with Posterior Fossa Tumour Following Lumbar Puncture and Surgery. BMJ Case Rep Apr 15;2014. pii: bcr Brun S, Esparza LA, Garcia G, Terry D, Huang J-M, Pavlyukov MS, Li X-N, Grant G, Crawford JR, Levy M, Conway EM, Smith L, Nakano I, Wang Q, Wechsler-Reya RJ. Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma. Oncogene 2014 Rao KI, Levy ML, Crawford JR. Giant Suprasellar Arachnoid Cyst Presenting with Precocious Puberty. BMJ Case Rep Aug 19;2014. pii: bcr Rao K, Shayan K, Levy ML. Crawford JR. Giant Pericallosal Lipoma Associated with Epilepsy and Chronic Headaches in a Child. BMJ Case Rep Oct 27;2014. Wong V, Lefloch N, Crawford JR. Fatal Gastrointestinal Haemorrhage in a Young Boy with Newly Diagnosed Metastatic Medulloblastoma on High Dose Dexamethasone. Case Rep Pediatr. 2014;2014: Fogal V, BabicI, Chao Y, Pastorino S, Mukthavaram R, Jiang P, Cho YC, Pingle SC, Crawford JR, Piccioni DE, Kesari S. Mitochondrial p32 is upregulated in Myc expressing brain cancers and mediates glutamine addiction. Oncotarget Jan 20;6(2): Jankowski PP, Crawford JR, Khanna P, Malicki DM, Ciacci JD, Levy ML. Pituitary tumor apoplexy in adolescents. World Neurosurg Dec 17. pii: S (14) [Epub ahead of print] Bykowski J, Kruk P, Gold JJ, Glaser CA, Sheriff H, Crawford JR. Acute Pediatric Encephalitis Neuroimaging: Single Institution Series as Part of the California Encephalitis Project. Pediatr Neurol Jun;52(6): Rismanchi N, Gold JJ, Sattar S, Glaser C, Sheriff H, Proudfoot J, Mower A, Crawford JR, Nespeca MN, Wang SW. Epilepsy after resolution of presumed childhood encephalitis. Pediatr Neurol Jul;53(1): Chen DY Crawford JR Hodgkin s Lymphoma in an Adolescent Previously Treated with Surgical Resection of Third Ventricular Juvenile Pilocytic Astrocytoma. BMJ Case Rep Jun 25;2015. Mitchell Diccianni MD Williams RT, Yu AL, Diccianni MB, Theodorakis EA, Batova A. (2013) Renal cancer-selective Englerin A induces multiple mechanisms of cell death and autophagy. J Exp Clin Cancer Res. 32(1):57 Kelner MJ, Diccianni MB, Yu AL, Rutherford MR, Estes LA, Morgenstern R. (2014) Absence of MGST1 mrna and protein expression in human neuroblastoma cell lines and primary tissue. Free Radic Biol Med. 69C: PMID: Endnote: {Kelner, 2014 #1876} Williams RT, Barnhill LM, Kuo HH, Lin WD, Batova A, Yu AL, Diccianni MB. (2014) Chimeras of p14arf and p16: Functional Hybrids with the Ability to Arrest Growth. PLoS One. 9(2):e PMID: Endnote: {Williams, 2014 #1878} Mickaël Terme; Mylène Dorvillius; Denis Cochonneau; Tanguy Chaumette; Wenhua Xiao; Mitchell B. Diccianni; Jacques Barbet; Alice L. Yu; François Paris; Linda L. Sorkin; Stephane Birkle (2014). Chimeric antibody c.8b6 to O-acetyl-GD2 mediates the same efficient anti-neuroblastoma effects than therapeutic ch14.18 antibody to GD2 without antibody induced allodynia. PLoS One Feb 10;9(2):e87210 PMID: Endnote: {Terme, 2014 #1936} Barnhill, LM, Williams, RT, Cohen, O, Kim, Y, Batova, A, Mielke, JA, Messer, K, Pu, M, Bao, L, Yu, AL, Diccianni, MB. (2014) High expression of CAI2, a 9p21-embedded long non-coding RNA, contributes to advanced stage neuroblastoma. Cancer Res. 74(14); PMID: Endnote: {Barnhill, 2014 #1924} Donald L. Durden, MD, PhD De, P., Dey, N., Terakedis, B., Bersagel, L., Trudel, S., Makale, M., Garlich, J.R., Durden, D.L. An integrin-targeted, pan phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo. Cancer Chemother. Pharmacol. 74: 867, Morales, G., Garlich, J.R. Su, J.D., Peng, X-D., Newblom, K., Weber, K. and Durden, D.L. Synthesis and cancer stem cell-based activity of substituted 5-morpholino-7H-thieno [3,2-b]pyran-7-ones designed as next generation PI3 kinase inhibitors. J. Med. Chem., 56: 1922, Hartman, L., Crawford, J.R., Makale, M. Milburn, M., Joshi, S., Salazar, A.M., Hasenauer, B., MacDonald, T.J. and Durden D.L. A Phase II trial of PolyICLC in the management of newly diagnosed and recurrent pediatric brain tumors. J. Ped. Hem. Oncology, 36: 451, Muh, C.R., Joshi, S., Singh, A.R., Kesari, S., Durden, D.L. and Makale, M.T. PTEN status mediates 2ME2 anti-tumor efficacy in preclinical glioblastoma models; role of HIF1 α suppression. J. Neurooncology, 116: 89, Joshi, S., Singh, A.R., Zulcic, M., Bao, L., Messer, K., Ideker, T., Dutkowski, J. and Durden, D.L. Rac2controls tumor growth, metastasis and M1 to M2 macrophage differentiation in vivo. PLoS One. 25: e95893, Singh, A.R., Peirce, S.B., Joshi, S., and Durden, D.L. PTEN and PI-3 kinase inhibitors control LPS signaling and lymphoproliferative response in the CD19+B cell compartment. Experimental Cell Research. 327: 78, Joshi, S., Singh, A.R., Zulcic, M. and Durden, D.L. PTEN/PI-3 kinase signaling axis regulated hypoxia induced HIF1 α and HIF2 α stability in macrophages and controls tumor growth, angiogenesis and metastasis. Mol. Canc. Res. 10: 1520, Joshi, S., Singh, A.R., Zulcic, M. and Durden, D.L. PKC desensitizes Fcγ receptor signaling and leads to inhibition of phagocytosis through an activation of protein tyrosine phosphatase, SHP-1 action. BMC Immunology. 15: 18, Joshi, S., Singh, A.R. and Durden, D.L. MDM2 regulates hypoxic HIF1 α stability in an E3 ligase. Proteasome and PTEN-PI-3 kinase- AKT dependent manner. J. Biol. Chem., 289: 22785, Joshi, S., Singh, A.R. and Durden, D.L. Pan-PI-3 kinase inhibitor SF1126 shows antitumor and antiangiogenic activity in renal cell carcinoma. Cancer Chemother Pharmacol., 75: 595,2015. William D. Roberts, MD Mitchell D, Bergendahl G, Ferguson W, Roberts W, Higgins T, Ashikaga T, DeSarno M, Kaplan J, Kraveka J, Eslin D, Werff AV, Hanna GK, Sholler GL. A phase 1 trial of TPI 287 as a single agent and in combination with temozolomide in patients with refractory or recurrent neuroblastoma or medulloblastoma. Pediatr Blood Cancer Jul 31; doi: /pbc PMID: Aristizabal P, Fuller S, Rivera R, Beyda D, Ribeiro RC, Roberts W. Improving Pediatric Cancer Care Disparities across the United States Mexico Border: Lessons Learned from a Transcultural Partnership between San Diego and Tijuana. Front. Public Health Jun 22; 3:159. doi: /fpubh PMID: Saulnier Sholler GL, Gerner EW, Bergendahl G, MacArthur RB, VanderWerff A, Ashikaga T, Bond JP, Ferguson W, Roberts W, Wada RK, Eslin D, Kraveka JM, Kaplan J, Mitchell D, Parikh NS, Neville K, Sender L, Higgins T, Kawakita M, Hiramatsu K, Moriya SS, Bachmann AS. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma. PLoS One May 27; 10(5):e doi: /journal.pone PMID: Saulnier Sholler GL, Bond JP, Bergendahl G, Dutta A, Dragon J, Neville K, Ferguson W, Roberts W, Eslin D, Kraveka J, Kaplan J, Mitchell D, Parikh N, Merchant M, Ashikaga T, Hanna G, Lescault PJ, Siniard A, Corneveaux J, Huentelman M, Trent J. Feasibility of implementing molecular-guided therapy for the treatment of patients with relapse or refractory neuroblastoma. Cancer Med Feb 26. doi: /cam PMID: Kang Y, Hodges A, Ong O, Roberts W, Piermarocchi C, Paternostro G. Identification of Drug Combinations Containing Imatinib for Treatment of BCR-ABL+ Leukemias. PLoS One, 2014 Jul 16; 9(7):e doi: /journal.pone ecollection PMID: Walsh KM, de Smith AJ, Welch TC, Smirnov I, Cunningham MJ, Ma X, Chokkalingam AP, Dahl GV, Roberts W, Barcellos LF, Buffler PA, Metayer C, Wiemels JL. Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B-cell ALL. American Journal of Hematology, 2014 Apr 3. doi: / ajh PMID: Huang JS, Dillon L, Terrones L, Schubert L, Roberts W, Finklestein J, Swartz MC, Norman GJ, Patrick K. Fit4Life: A Weight Loss Intervention for Children who have survived Childhood Leukemia. Pediatric Blood & Cancer, 2014 Jan 16. doi: /pbc PMID: Tiziani S, Kang Y, Harjanto R, Axelrod J, Piermarocchi C, Roberts W, Paternostro G. Metabolomics of the Tumor Microenvironment in Pediatric Acute Lymphoblastic Leukemia. PLoS One, 2013 Dec 13;8(12):e PMID: Walsh KM, de Smith AJ, Chokkalingam AP, Metayer C, Roberts W, Barcellos LF, Wiemels JL, Buffler PA. GATA3 risk alleles are associated with ancestral components in Hispanic Children with ALL. Blood, 2013 Nov 7;122(19): PMID: Deborah E. Schiff, MD Aristizabal P, Singer J, Cooper R, Wells KJ, Nodora J, Milburn M, Gahagan S, Schiff DE, Martinez ME. Participation in pediatric oncology research protocols: Racial/ethnic, language and age-based disparities. Pediatr Blood Cancer. 62: , Rahn D, Mundt AJ, Murphy J, Schiff D, Adams J, Murphy K. Clinical outcomes of palliative radiotherapy for children. Practical Rad Onc. 5:183-7, Adams J, Auger J, Schiff D. Outcome of indwelling tunneled PleurX catheter placement in pediatric and young adult patients with malignant effusions. Pediatr Blood Cancer. 61: , Sturm A, Baack EC, Armstrong MB, Schiff D, Zia A, Savasan S, de la Chapelle A, Tanner S. Hereditary Intrinsic Factor Deficiency in Chaldeans. JIMD Reports. 7:13-18, Courtney Thornburg, MD, MS Sobush KT, Thornburg CD, Voynow JA, Davis SD, Peterson- Carmichael SL. A 2-year old girl with co-inherited cystic fibrosis and sickle cell-beta+ thalassemia presenting with recurrent vasoocclusive events during cystic fibrosis pulmonary exacerbations: a case report. J Med Case Rep : 203. Thornburg CD. Sickle cell anemia: time for personalized prescription of hydroxyurea? Focus on OATP1B transporters modulate hydroxyurea pharmacokinetics. Am J Physiol Cel Physiol (12): C Boateng L, Puffer E, Allen T, Bonner M, Thornburg CD. Adherence to secondary stroke prevention in children with sickle cell anemia: family and child perspectives. J Blood Disorders Transf :4. Bekele E, Thornburg CD, Brandow AM, Sharma M, Smaldone AM, Jin Z, Green NS. Do difficulties in swallowing medication impede the use of hydroxyurea in children? Pediatr Blood Cancer (9): Willen S, Thornburg CD, Lantos P. Travelers with sickle cell disease. J Travel Med (5): Hinson A, Owen W, Prose N, Parikh S, Thornburg C. Congenital hemophagocytic lymphohistiocytosis presenting as thrombocytopenia in a newborn. J Pediatric Hematol Oncol (4): Mahajerin A, Thornburg CD. Hospital Acquired Venous Thromboembolism in Children: Call-to-Action. J Pediatr (4): Hankins JS, Aygun B, Nottage K, Thornburg C, Smeltzer MP, Ware RE, Wang WC. From infancy to adolescence: fifteen years of continuous treatment with hydroxyurea in sickle cell anemia. Medicine (Baltimore) (28):e215. Rice HE, Englum BR, Rothman J, Leonard S, Reiter A, Thornburg C, Brindle M, Wright N, Heeney MM, Smithers C, Brown RL, Kalfa T, Lange JC, Cada M, Oldham KT, Scott JP, St. Peter S, Sharma M, Davidoff AM, Nottage K, Bernabe K, Wilson DB, Dutta S, Glader B, Crary SE, Dassinger MS, Dunbar L, Islam S, Kumar M, Rescorla F, Bruch B, Campbell A, Austin M, Sidonio R, Blakely ML and the Splenectomy in Congenital Hemolytic Anemia (SICHA) Consortium. Clinical Outcomes of Splenectomy in Children: Report of the Splenectomy in Congenital Hemolytic Anemia (SICHA) Registry. Am J Hematol (3): Anderson LM, Allen TM, Thornburg CD, Bonner MJ. Fatigue in children with sickle cell disease: association with neurocognitive and social-emotional functioning and quality of life. J Pediatr Hematol Oncol (8): Estepp JH, Melloni C, Thornburg CD, Wiczling P, Rogers Z, Rothman JA, Green NS, Liem R, Brandow AM, Crary SE, Howard TH, Morris HM, Lewandowski A, Garg U, Jusko WJ, Neville KA; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee. J Clin Pharmacol doi: 154 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 155

79 /jcph.598. PMID: Englum BR, Rothman J, Leonard S, Reiter A, Thornburg C, Brindle M, Wright N, Heeney MM, Jason Smithers C, Brown RL, Kalfa T, Langer JC, Cada M, Oldham KT, Scott JP, Peter SD, Sharma M, Davidoff AM, Nottage K, Bernabe K, Wilson DB, Dutta S, Glader B, Crary SE, Dassinger MS, Dunbar L, Islam S, Kumar M, Rescorla F, Bruch S, Campbell A, Austin M, Sidonio R, Blakely ML, Rice HE; Splenectomy in Congenital Hemolytic Anemia (SICHA) Consortium. Hematologic outcomes after total splenectomy and partial splenectomy for congenital hemolytic anemia. J Pediatr Surgery doi: /j.jpedsurg Luchtman-Jones L, Pressel S, Hilliard L, Brown C, Smith MG, Thompson AA, Lee MT, Rothman J, Rogers ZR, Owen W, Imran H, Thornburg C, Kwiatkowski JL, Aygun B, Nelson S, Roberts C, Guager C, Piccone C, Kalfa T, Alvarez O, Hassell K, Davis BR, Ware RE. Effects of hydroxyurea treatment for patients with hemoglobin SC disease. Am J Hematol doi: /ajh Non-authored publications - Thornburg: Goldenberg NA, Abshire T, Blatchford PJ, Fenton LZ, Halperin JL, Hiatt WF, Kesller CM, Kittelson JM, Manco-Johnson MJ, Spyropoulos AC, Steg PG, Stence NV, Turpie AG, Schulman S; Kids- DOTT Trial Investigators. Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): pilot/feasibility phase findings. J Thromb Haemost (9): Y.T. Udaka, MD Y.T. Horikawa, T.Y. Udaka, J.K. Crow, J.I. Takayama, & M.T. Stein. Anxiety associated with asthma exacerbations and overuse of medication: the role of cultural competency. Journal of Developmental & Behavioral Pediatrics Feb-Mar; 35(2):154-7 Y.T. Udaka, K. Shayan, N.A. Chuang, & J.R. Crawford. Atypical presentation of atypical teratoid rhabdoid tumor in a child. Case Reports in Oncological Medicine May Jing Yang, PhD Janine M. Low-Marchelli, Veronica C. Ardi, Andrew T. Chang, Nico van Rooijen, James P. Quigley, and Jing Yang. (2013) Twist1 induces CCL2 and recruits macrophages to promote angiogenesis. Cancer Research. 73(2): (Cover Highlight) Helicia Paz, Navneeta Pathak, and Jing Yang. (2013) Invading one step a time: the role of invadopodia in tumor metastasis. Oncogene. 33(33): Jeff H. Tsai, and Jing Yang. (2013) Epithelial-Mesenchymal plasticity in carcinoma metastasis. Genes & Development. 27 (20): Shan Li, and Jing Yang. (2014) Ovol proteins: Guardians against EMT during epithelial differentiation. Developmental Cell. 29 (1): 1-2. Xuefeng Wu, Weizhou Zhang, Joan Font-Burgada, Trenis Palmer, Alexander S. Hamil, Subhra K. Biswas, Michael Poidinger, Nicholas Borcherding, Qing Xie, Lesley G. Ellies, Nikki K. Lytle, Li-Wha Wu, Raymond G. Fox, Jing Yang, Steven F. Dowdy, Tannishtha Reya, and Michael Karin. (2014) Ubiquitin-conjugating enzyme Ubc13 controls breast cancer metastasis through a TAK1-p38 MAP kinase cascade. PNAS. 111 (38): Haeyun Jung, Laurent Fattet, and Jing Yang. (2014) Molecular Pathways: Linking Tumor Microenvironment to Epithelial- Mesenchymal Transition in Metastasis. Clinical Cancer research. 21(5); 1-7. Haeyun Jung and Jing Yang. (2015) Unraveling the TWIST between EMT and Cancer Stemness. Cell Stem Cell. 16 (1): 1-2. Andrew T. Chang, Yuanjie Liu, Kasirajan Ayyanathan, Chris Benner, Yike Jiang, Jeremy W. Prokop, Helicia Paz, Dong Wang, Hai-Ri Li, Xiang-Dong Fu, Frank J. Rauscher III,* and Jing Yang*. (2015) An evolutionarily conserved DNA architecture determines target specificity of the Twist-family bhlh transcription factors. (*cocorresponding authors) Genes & Development. 29 (6): Spencer C. Wei, Laurent Fattet, Jeff H. Tsai, Yurong Guo, Vincent H. Pai, Hannah E. Majecki, Albert C. Chen, Robert L. Sah, Susan S. Taylor, Adam J. Engler, Jing Yang. (2015) Matrix stiffness drives Epithelial-Mesenchymal Transition and tumor metastasis via a Twist1-G3BP2 mechanotransduction pathway. Nature Cell Biology. 17(5): Spencer C. Wei, Laurent Fattet, Jing Yang. (2015) The Forces behind EMT and tumor metastasis. Cell Cycle. July 17:1-2 [Epub ahead of print]. Janet Yoon, MD Gabel BC, Levy ML, Yoon J and Crawford JR. Ring-enhancing pontine lesion in a young boy. BMJ Case Reports. 2013, published online 13 September 2013, doi: /bcr Chuang NA, Yoon JM, Newbury RO and Crawford JR. Glioblastoma multiforme arising from dysembryoplastic neuroepithelial tumor in a child in the absence of therapy. Journal of Pediatric Hematology/ Oncology. 2014, doi: /mph Gabel BC, Yoon J, Levy ML and Crawford JR. A diffuse intrinsic pontine glioma in a neonate diagnosed by MRI. BMJ Case Reports. 2014: published online 21 January 2014, doi: /bcr Gabel BC, Yoon J and Crawford JR. Clinical isolated syndrome mimicking focal brainstem glioma in a child. BMJ Case Reports. 2014, published online 10 March 2014, doi: /bcr Yoon J, Martin A, Malicki D, Newbury R and Crawford J. Unusual spinal cord tumor in a 16-month-old child. Brain Pathology. 2015, 25(6): Udaka YT, Yoon JM, Malicki DM, Khanna PC, Levy ML, Crawford JR. Atypical Teratoid Rhabdoid Tumor in a Teenager with Unusual Infiltration Into the Jugular Foramen. World Neurosurgery. 2015, 84(6): 2075.e13-e16. Murphy EP, Mo J, Yoon JM. Secondary Hemophagocytic Lymphohistiocytosis in a Patient with Favorable Histology Wilms Tumor. Journal of Pediatric Hematology/Oncology. 2015, 37(8): e494-e496. Alice L. Yu, MD, PhD Chan Y.T., Lin Y.C., Lin R.J., Kuo H.H., Thang W.C., Chiu K.P., Yu A.L.* Concordant and discordant regulation of target genes by mir- 31 and its isoforms. PLoS One. 2013, 8(3): e Chang B.M., Lin H.H., Su L.J., Lin W.D., Lin R.J., Tzeng Y.K., Lee R.T., Lee Y.C., Yu A.L.*, Chang H.C.* Highly Fluorescent Nanodiamonds Protein-Functionalized for Cell Labeling and Targeting. Advanced Functional Materials. 2013, 23(46): Chang W.W., Lin R.J., Yu J., Chang W.Y., Fu C.H., Lai A.C., Yu J.C., Yu A.L.* The expression and significance of insulin-like growth factor-1 receptor and its pathway on breast cancer stem/progenitors. Breast Cancer Res. 2013, 15(3): R39. Chen Y.J., Thang M.W., Chan Y.T., Huang Y.F., Ma N., Yu A.L., Wu C.Y., Hu M.L., Chiu K.P.* Global assessment of Antrodia cinnamomea-induced microrna alterations in hepatocarcinoma cells. PLoS One. 2013, 8(12): e Huang Y.L., Hung J.T., Cheung S.K., Lee H.Y., Chu K.C., Li S.T., Lin Y.C., Ren C.T., Cheng T.J., Hsu T.L., Yu A.L.*, Wu C.Y.*, Wong C.H.* Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer. Proc Natl Acad Sci U S A. 2013, 110(7): Kreissman S.G., Seeger R.C., Matthay K.K., London W.B., Sposto R., Grupp S.A., Haas-Kogan D.A., Laquaglia M.P., Yu A.L., Diller L., Buxton A., Park J.R., Cohn S.L., Maris J.M., Reynolds C.P., Villablanca J.G. Purged versus non-purged peripheral blood stemcell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial. Lancet Oncol. 2013, 14(10): Sawant R.C., Hung J.T., Chuang H.L., Lin W.S., Chen W.S., Yu A.L.*, Luo S.Y.* Synthesis of Hydroxylated Analogues of a-galactosyl Ceramide (KRN7000) with varying stereochemistry. Eur J Org Chem. 2013, 2013(33): Tsai Y.C., Huang J.R., Cheng J.Y., Lin J.J., Hung J.T., Wu Y.Y., Yeh K.T., Yu A.L. A Prevalent Cancer Associated Glycan, Globo H Ceramide, Induces Immunosuppression by Reducing Notch1 Signaling. Journal of Cancer Science & Therapy. 2013, 5: Unguru Y.*, Joffe S., Fernandez C.V., Yu A.L. Ethical issues for control-arm patients after revelation of benefits of experimental therapy: a framework modeled in neuroblastoma. J Clin Oncol. 2013, 31(5): Williams R.T., Yu A.L., Diccianni M.B., Theodorakis E.A., Batova A.* Renal cancer-selective Englerin A induces multiple mechanisms of cell death and autophagy. J Exp Clin Cancer Res. 2013, 32(1): 57. Barnhill L.M., Williams R.T., Cohen O., Kim Y., Batova A., Mielke J.A., Messer K., Pu M., Bao L., Yu A.L.*, Diccianni M.B.* High Expression of CAI2, a 9p21-Embedded Long Noncoding RNA, Contributes to Advanced-Stage Neuroblastoma. Cancer Res. 2014, 74(14): Fu C.H., Lin R.J., Yu J., Chang W.W., Liao G.S., Chang W.Y., Tseng L.M., Tsai Y.F., Yu J.C., Yu A.L.* A Novel Oncogenic Role of Inositol Phosphatase SHIP2 in ER-Negative Breast Cancer Stem Cells: Involvement of JNK/Vimentin Activation. Stem Cells. 2014, 32(8): Huang J.R., Tsai Y.C., Chang Y.J., Wu J.C., Hung J.T., Lin K.H., Wong C.H., Yu A.L.* alpha-galactosylceramide but not phenyl-glycolipids induced NKT cell anergy and IL-33-mediated myeloid-derived suppressor cell accumulation via upregulation of egr2/3. J Immunol. 2014, 192(4): Hung J.T., Tsai Y.C., Lin W.D., Jan J.T., Lin K.H., Huang J.R., Cheng J.Y., Chen M.W., Wong C.H.*, Yu A.L.* Potent adjuvant effects of novel NKT stimulatory glycolipids on hemagglutinin based DNA vaccine for H5N1 influenza virus. Antiviral Res. 2014, 107: Kelner M.J., Diccianni M.B., Yu A.L., Rutherford M.R., Estes L.A., Morgenstern R. Absence of MGST1 mrna and protein expression in human neuroblastoma cell lines and primary tissue. Free Radic Biol Med. 2014, 69: Lin J., Chang Y.J., Yang W.B., Yu A.L.*, Wong C.H.* The Multifaceted Effects of Polysaccharides Isolated from Dendrobium huoshanense on Immune Functions with the Induction of Interleukin-1 Receptor Antagonist (IL-1ra) in Monocytes. PLoS One. 2014, 9(4): e Lin J.J., Huang C.S., Yu J., Liao G.S., Lien H.C., Hung J.T., Lin R.J., Chou F.P., Yeh K.T., Yu A.L.* Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/ disialoganglioside identify their tumor stem cells. Breast Cancer Research. 2014, 16(2): R29. Sonawane P., Cho H.E., Tagde A., Verlekar D., Yu A.L., Reynolds C.P., Kang M.H. Metabolic characteristics of 13-cis retinoic acid (isotretinoin) and anti-tumor activity of the 13-cis retinoic acid metabolite 4-oxo-13-cis retinoic acid in neuroblastoma. Br J Pharmacol. 2014, 171(23): Terme M., Dorvillius M., Cochonneau D., Chaumette T., Xiao W., Diccianni M.B., Barbet J., Yu A.L., Paris F., Sorkin L.S., Birkle S.* Chimeric antibody c.8b6 to O-acetyl-GD2 mediates the same efficient anti-neuroblastoma effects as therapeutic ch14.18 antibody to GD2 without antibody induced allodynia. PLoS One. 2014, 9(2): e Williams R.T., Barnhill L.M., Kuo H.H., Lin W.D., Batova A., Yu A.L., Diccianni M.B.* Chimeras of p14arf and p16: functional hybrids with the ability to arrest growth. PLoS One. 2014, 9(2): e Chang C.H., Fan T.C., Yu J.C., Liao G.S., Lin Y.C., Shih A.C., Li W.H., and Yu A.L.* The prognostic significance of RUNX2 and mir-10a/10b and their inter-relationship in breast cancer. Journal of Translational Medicine. 2014, 12: 257. Cheng J.Y., Wang S.H., Lin J., Tsai Y.C., Yu J., Wu J.C., Hung J.T., Lin J.J., Wu Y.Y., Yeh K.T., and Yu A.L.* Globo-H ceramide shed from cancer cells triggers translin-associated factor X-dependent angiogenesis. Cancer Research. 2014, 74: Jennifer Yu, MD Lin G, Field JJ, Yu JC, Ken R, Neuberg D, Nathan D, Linden J. NF-kB is activated in CD4+ inkt cells by sickle cell disease and mediates rapid induction of adenosine A2A receptors. PLOS One Oct 4;8(10):e Noris P, Favier R, Alessi MC, Geddis AE, Kunishima S, Heller PG, Giordano P, Niederhoffer K, Bussel JB, Podda GM, Vianelli N, Kersseboom R, Pecci A, Gnan C, Marconi C, Auvrignon A, Cohen W, Yu JC, Iguchi A, Imahiyerobo AM, Boehlen F, Ghalloussi D, De Rocco D, Magini P, Civaschi E, Biino G, Seri M, Saviola A & Balduini C. ANKRD26-related thrombocytopenia and myeloid malignancies. Blood Sept 12;122(11): BOOK CHAPTERS John R. Crawford, MD JR Crawford. HHV-6 and Cancer, HUMAN HERPESVIRUS-6A & 6B In: A clinical Diagnostic Handbook, Third Edition, Louis Flammand Ed. Academic Press/Elsevier. Levy ML, Crawford JR, Reeves A, Abbasifard S, Altimimi M. Pediatric Neurosurgery: Endoscopic Third Ventriculostomy In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Hong D, Reeves A. Pediatric Neurosurgery: Slit Ventricle Syndrome In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Reeves A. Pediatric Neurosurgery: Endoscopic Cerebellar Medulloblastoma In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Reeves A, Abbasifard S. Pediatric Neurosurgery: Brainstem Glioma In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Reeves A, Abbasifard S. Pediatric Neurosurgery: Hypothalamic Hamartoma In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Reeves A, Altimimi M. Pediatric Neurosurgery: Pilocytic Astrocytoma In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Altimimi M. Pediatric Neurosurgery: Spasticity In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 157

80 Donald L. Durden, MD, PhD Joshi, S. Singh, A., Hartman, L., Ahn, H., Zulcic, M. and Durden, D.L. New therapeutic approaches for Neuroblastoma, In: Neuroblastoma. Ed H. Shimada. Intech, Heym KM, Thornburg C. Hematology In Hannaman RA (ed) In: MedStudy Pediatrics Review Core Curriculum. 6th Edition. Colorado Springs, Colorado: MedStudy. Courtney Thornburg, MD, MS Thornburg C. Hematologic issues in the high-risk infant In: Malcolm WF (ed). Beyond the NICU: Comprehensive care of the high-risk infant (pp ). Mc Graw Hill Education, Thornburg C. Heparin induced thrombocytopenia and thrombosis in children In: Goldenerg N and Manco-Johnson M. Pediatric Thrombotic Disorders (pp158-65). 1st Edition. Cambridge University Press, AWARDS & HONORS M. Paula Aristizabal, MD, MS Best SIOP Poster Award, 45 Congress International Society of Pediatric Oncology. Hong Kong American Society of Hematology- Clinical Research Training Institute Award AACR Scholar-in-Training Award, Center to Reduce Cancer Health Disparities of the National Cancer Institute, American Association for Cancer Research 2014 Puentes Symposium Scholar Award Puentes Consortium Rice University 2015 University of California Office of the President Team Science Scholar 2015 John R. Crawford, MD, MS 2013: Junior Faculty Teaching Award Department of Neurosciences, University of California, San Diego 2014: Junior Faculty Teaching Award Department of Neurosciences, University of California, San Diego 2015 Senior Faculty Teaching Award Department of Neurosciences, University of California San Diego 2015 Leonard Tow Humanism Award in Medicine Nominee 2015 Top Pediatric Neurologist San Diego Magazine Donald L. Durden, MD, PhD Editorial Board, Molecular Cancer Research (MCR)(AACR), 2015 Jenny M. Kim, MD US News Top Doctor Pediatric Hematology and Oncology, Anemia, Sickle Cell Disease, 2013 San Diego Magazine Top Doctor Pediatric Hematology and Oncology, 2014 Dennis Kuo, MD, MS Alpha Omega Alpha Honor Medical Society, April, 2015 William D. Roberts, MD Rady Children s Hospital Annual Excellence in Clinical Care Award, 2015 Jing Yang, PhD 01/ /2015 American Cancer Society Research Scholar 05/ /2015 The Hartwell Foundation Investigator Janet Yoon, MD San Diego Magazine Top Doc, Pediatric Hematology/Oncology, UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 159

(Video) Comprehensive Review - PART 1

81 Hospital Medicine 160 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 161

82 INTRODUCTION FACULTY The Division of Pediatric Hospital Medicine (PHM) began in 1978 by Dr. Irvin Buzz Kaufman and is considered the oldest pediatric program in the nation. The Division continues to serve patients needing comprehensive general inpatient care and to teach future physicians the art and science of inpatient medicine. The Division provides inpatient care at Rady Children s Hospital-San Diego (RCHSD); Palomar Medical Center, located in the northeastern part of San Diego County; and Sharp Grossmont Hospital, located in the eastern part of San Diego County. These facilities are part of the larger Rady Children s Hospital and Health Center (RCHHC) system in San Diego and Riverside counties. The hospitalists serve as a regional clinical resource for community physicians and emergency departments to determine the need for acute care admission, discuss alternatives to admission, and provide a second opinion for patients with diagnostic challenges. All PHM members are board-certified pediatricians with acquired expertise in different fields of hospital medicine and half have at least 10 years in PHM. Most have had additional post-residency training through Chief Residency and/or fellowship or subspecialty certification including hospice and palliative care medicine, clinical dermatology, critical care and pediatric hospital medicine. The Division developed one of the first 3 PHM Fellowship training programs in the country, and has been involved in national work for committees and societies that advance care of pediatric inpatients such as the Children s Hospital Association, Institute for Healthcare Improvement, American Academy and others. The hospitalists work closely with hospital staff and administrative leadership to optimize patient care and resource use across the healthcare system. The Division is proud to be the inpatient care providers for the vast majority of asthmatic inpatients in the county and thereby help the hospital receive superior scores in US News and World Report for success with asthma inpatients and management of asthma patients. Erin Stucky Fisher, MD, MHM Clinical Professor Interim Chief PHM Fellowship Director Julia Beauchamp-Walters, MD Clinical Professor Laurie Bernard-Stover, MD Clinical Professor ; PHM Clinical Director Melissa Cameron, MD Staff Physician DIVISION FAST FACTS $1.3 Million in Research Grants Over 5,000 admissions & 1,200 emergency transports coordinated Alicia Cantu, MD Associate Clinical Professor Weijen Chang, MD Staff Physician Jennifer L. Davis, MD Assistant Clinical Professor Ami Doshi, MD Associate Clinical Professor MAJOR PLANS AND GOALS To continue to provide excellence in clinical care, education, quality improvement, research, and advocacy on and for hospitalized infants, children, and adolescents To evolve existing clinical service lines and help advance the Accountable Care Model to meet the needs of our patients Daniel Hershey, MD Associate Clinical Professor Elizabeth Mannino Avila, MD Assistant Clinical Professor Sara M. Marchese, MD Associate Clinical Professor Paul Parker, MD Staff Physician To initiate new programs, such as include sonography, telemedicine, and care of the adult aged patient, Community Site Physicians: Priya Jain, MD (photo not available) fellowship and academic work, and will develop these areas via new faculty hiring and other collaborations. Sara Rourke, MD (photo not available) Heather Pierce, MD Associate Clinical Professor Kyung Rhee, MD, MSc Associate Clinical Professor ; PHM Research Director Brian Williams, MD Assistant Clinical Professor of Internal Medicine and Pediatrics 162 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 163

83 The Division admits approximately one third of all RCHSD patients, and serves as attending for all general pediatric admissions. Patients may have common or complex problems and include those otherwise healthy or that have complex medical and surgical conditions. In addition to serving as attending of record for patients, members perform consultation for sub-specialty patients, provide moderate sedation, and serve as medical control physician for the busy non-neonatal critical transport service. Additionally, the hospitalists provide acute and ongoing care to skilled nursing and subacute level convalescent patients at the Bernardy Center for Medically Fragile Children, located on the RCHSD campus. This past year, the division performed over 5000 admissions, coordinated 1200 emergency transports, and provided post-acute care for over 100 medically fragile children. The Hospital Medicine Service at the community sites began at Palomar Hospital in 2006 and Sharp Grossmont in The north county Palomar unit is part of a larger Rady program that includes newborn nursery and the neonatal intensive care unit. The census at both of these non-resident Rady-licensed units ranges from 5 to 12 patients. The Division is pleased to direct and staff the medical care system for the Juvenile Hall Program for San Diego and Imperial Counties. Members care for the common and complex medical needs of juveniles who are incarcerated at the main site at Kearney and camps. Telemedicine is used to support a more remote program farther east, closer to the Arizona border. The hospitalists fulfill many local leadership roles including: For RCHSD: Co-Director, Children s Emergency Transport (non-neonatal) (JB) Co-Chair, Family Centered Care Committee (HP) Director of Graduate Medical Education (HP) Medical Consultant, Home Care Services (JB) Medical Director, Inpatient Services (LBS) Medical Director, Quality Improvement (ESF) Medical Director, Bernardy Center for Medically Fragile Children Subacute Unit (JB) Medical Director, Palomar and Sharp Grossmont Pediatric Units (ESF) Medical Staff, Department Chair (LBS) Medical Staff, Chair, Pharmacy and Therapeutics Committee (DH) Medical Staff, Chair, Quality Improvement Committee (ESF) Medical Staff, Chair, Sedation Services Outside the Operating Room (DH) FELLOWS Michelle Edmunds, MD, 1st year, UCSD Maria Huang, MD, 1st year, UCSD CLINICAL ACTIVITIES 164 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report For UC San Diego Department : Fellowship Director, Hospital Medicine (ESF) Director of Graduate Medical Education Quality and Safety (ESF) Pediatric Co-Champion, University of California Tobacco Cessation Network (BW) For Community Facility partners: Medical Director, Juvenile Hall Services, San Diego and Imperial Counties (AC) In addition, hospitalists serve as members of key committees including: for RCSSD/Medical Practice Foundation: Board of Directors, Billing, Credentialing and Quality, Contracts, Marketing, Service lines (Digestive, Respiratory); for RCHHC: Anaesthesia Services, Antimicrobial stewardship, Bioethics, Clinical Leadership Council, Code Blue, Information Technology, Infection Control, Medical Staff Executive, multiple Morbidity and Mortality Conferences, Network Governance (Clinical), Pediatric Leadership Council, Pediatric Department, Pharmacy and Therapeutics, Quality Improvement, Quality Safety Operations Council, Telemedicine and Value Analysis; for UCSD School of Medicine and the Department of Pediatrics: Academy of Clinician Scholars, Academic Review and Appraisal, Clinical Clerkship, Graduate Medical Education, Resident Intern Applicant Selection, Resident Clinical Competency Assessment. Nationally, members serve in leadership roles for the following organizations: American Academy Joint Council for Pediatric Hospital Medicine (AAP, SHM and Academic Pediatric Association joint body) Society of Hospital Medicine (SHM) Pediatrics Committee, SHM Board Expert panels such as the Mount Sinai Collaboration to Advance Pediatric Quality Measures (CAPQuaM) Expert Panel on Medication Reconciliation in Mental Health Members are also active in key national groups, such as: Academic Pediatric Association American Academy of Homecare Physicians American Academy of Hospice and Palliative Medicine, and National Hospice and Palliative Care Organization Providing exceptional education to trainees and other learners is central to the PHM Division. Members teach UCSD School of Medicine core courses for fourth year medical students. Members provide core teaching for the inpatient ward experience to the over 250 trainees who rotate on the ward annually at Rady campus. Trainees include UCSD and visiting medical students, and residents from UCSD (pediatric, medicine/pediatric, family medicine), Balboa Naval Medicine (pediatric), Pendleton (family practice), Scripps (family practice), and other visiting from outside programs. Faculty train learners in the art and science of medicine, using family centered rounds and performing bedside and didactic sessions. Faculty participate in morning report and other core resident educational sessions. The Division oversees the highly valued senior resident Clinical Pathologic Correlation series that matches each UCSD senior pediatric and medicine/pediatric resident with a faculty mentor to work through a patient case, learning clinical decision-making. The presentation is given in Grand Rounds format, thus also offering trainees the opportunity to hone skills in public speaking. The PHM Fellowship began in 2005 and is one of now 42 in the US and Canada. The 14 graduates to date have secured leadership positions in education, focused protected time in The Division recently appointed Dr. Kyung Rhee as Director of Research. Dr. Rhee is developing the infrastructure and activities to meet the research strategic plan jointly developed by Drs. Rhee and Fisher. The division has a long-standing relationship with Infectious Diseases and collaborates on a number of clinical trials and investigator-initiated research projects with these investigators. The division has a joint bronchiolitis project with the Emergency Medicine Division, and a separate project on obesity. Individual member s research focus areas include: Julia Beauchamp, MD Dr. Beauchamp-Walters area of scholarly focus is in both complex chronic post-acute care and emergency transport. Laurie Bernard Stover, MD Dr. Bernard Stover works as sub-investigator on a number of clinical trials related to antibiotic efficacy, and performs clinical case studies. Melissa Cameron, MD Dr. Cameron works in the area of simulation and in inpatient opportunities for immunization. Alicia Cantu, MD Dr. Cantu s focus is on access and assessment of medical care to at risk incarcerated youth. Weijen Chang, MD Dr. Chang studies high value cost conscious care and the interface between pediatric and adult inpatient medicine. TEACHING ACTIVITIES RESEARCH ACTIVITIES research, and other successes at institutions such as Cincinnati Children s, Lucile Packard Children s Hospital at Stanford, Lurie Children s in Chicago, UCSD and others. The fellowship continues to receive competitive candidates from across the country. PHM Fellowships joined the NRMP fall match in 2015, and fellowship directors have robust, coordinated work on curriculum for the programs. Division members (ESF, HP) created and run the Innovative Quality Improvement Research in Residency (INQUIRY) Program, now in its 9th year. Over 60 pediatric medical and surgical residents and fellows are trained annually in core QI skills and perform a mentored project. Division faculty provide mentorship for multiple trainees annually, serve as editor and abstract reviewers for major conferences such as the Pediatric Academic Societies, Association of Pediatric Program Directors/Council on Medical Student Education in Pediatrics (COMSEP), and the American Academy of Pediatrics National Convention and Exhibition. Members perform journal reviews for journals such as Academic Pediatrics, Journal of Graduate Medical Education, BMJ Quality and Safety and others, and one serves as pediatric editor for The Hospitalist (WC). Ami Doshi, MD Dr. Doshi performs research in palliative care outcomes. Erin Stucky Fisher, MD Dr. Fisher performs research in quality improvement and education in areas such hospital discharge, team training, and teaching QI. She also leads and participates in clinical trials on antimicrobial treatment outcomes. Daniel Hershey, MD Dr. Hershey performs scholarly work related to drug interactions and performs clinical case studies. Elizabeth Mannino Avila, MD Dr. Mannino Avila s focus is on identifying and interpreting bacteremia in young infants. Heather Pierce, MD Dr. Pierce focuses on bronchiolitis and quality improvement around the care of this disease. Brian Williams, MD Dr. Williams is co-leading University of California medical centers efforts on smoking cessation in pediatrics. He also performs research on spinal rod infections with infectious diseases and orthopedic colleagues Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 165

84 PUBLICATIONS *Hasegawa K, Pate BM, Mansbach JM, Macias CG, Fisher ES, Piedra PA, Espinola JA, Sullivan AF, Camargo CA Jr. Risk factors for requiring intensive care among children admitted to ward with bronchiolitis. Acad Pediatr Jan-Feb; 15(1): Doi: /j.acap Auger, K, Simon T, Cooperberg D, Gay J, Kuo D, Saysana M, Stille C, Fisher ES, Wallace S, Berry J, Coghlin D, Jhaveri V, Kairys S, Logsdon T, Shaikh U, Srivastava R, Starmer A, Wilkins V, Shen M. Summary of STARnet: Seamless Transitions And (Re)admissions Network. Pediatrics Jan;135(1): doi: / peds (Published online ahead of print 2014 Dec 8.) Coghlin DT, Leyenaar JK, Shen M, Bergert L, Engel R, Hershey D, Mallory L, Rassbach C, Woehrlen T, Cooperberg D.Pediatric Discharge Content: a multisite assessment of physician preferences and experiences. Hosp Pediatr Jan;4(1):9-15. PMID: Herzke C, Chang W, Leazer R. Things we do for no reason: the 48- hour rule-out sepsis in febrile infants. Journal of Hospital Medicine (accepted 2015). Macias CG, Mansbach JM, Fisher ES, Riederer M, Piedra PA, Sullivan AF, Espinola JA, and Camargo Jr CA. Variability in inpatient management of children hospitalized with bronchiolitis. Acad Pediatr Jan-Feb;15(1): doi: /j.acap (Published online ahead of print 2014 Nov 8). *Pierce H, Mansbach JM, Fisher ES, Macias CG, Pate BM, Piedra PA, Sullivan AF, Espinola JA, and Camargo Jr CA. Variability of Intensive Care Management for Children With Bronchiolitis. Hospital Pediatrics Apr;5(4): doi: /hpeds (Finalist for publication of the year, PHM Annual meeting 2015). Singh A, Rhee KK, Brennan JJ, Kuelbs C, El-Kareh R, Fisher ES. Who s My Doctor? Using an electronic tool to improve team member identification on an inpatient pediatrics team. Hospital Pediatrics. (Accepted 2015). Mirkinson L, Daru J, Fisher ES, Garber M, Hain PD, Narang AS, Quinonez R, Rauch DA. AAP Policy Statement: Guiding Principles for Pediatric Hospital Medicine Programs. Pediatrics Oct (4): doi: /peds *Samady W, Bush R, Pong A, Andrews A, Fisher ES. Predictors of Clostridium difficile infections in hospitalized children. J Hosp Med Feb; 9(2): doi: /jhm.2135 Samady W, Pong A, Fisher E. Risk Factors for the Development of C. difficile Infection in Hospitalized Children. Current Opinion in Pediatrics Oct; 26(5): *Schroeder AR, Mansbach JM, Stevenson M, Macias CG, Fisher ES, Besh Barcega, Sullivan AF, Espinola JA, Piedra PA, Camargo Jr. CA. Apnea in Children Hospitalized with Bronchiolitis. Pediatrics. 2013;132:1 8. doi: /peds Shen MW, Hershey D, Bergert L, Mallory L, Fisher ES, and Cooperberg D. Pediatric Hospitalists Collaborate to Improve Timeliness of Discharge Communication. Hospital Pediatrics. 2013; 3(3): doi: /hpeds BOOK CHAPTERS Bernard-Stover, L. Erythema Multiforme and Stevens Johnson Syndrome. In: Caring for the Hospitalized Child: A Handbook of Inpatient Pediatrics: AAP: 2013:71-76 (2016 update accepted.) Fisher, ES. Patient Safety in Pediatrics: A Case-Based Comprehensive Guide. In: Abha Agrawal, Editor. Patient Safety, p Springer New York, doi: / _16 Fisher, ES. Patient Safety. In: Caring for the Hospitalized Child, A Handbook of Inpatient Pediatrics, p AAP: 2013 (2016 update accepted.) Fisher, ES and Fisher, BC. Ventilation and Intubation. In: Caring for the Hospitalized Child, A Handbook of Inpatient Pediatrics, p AAP: 2013 (2016 update accepted.) Hershey D. Acute Abdomen. In: Caring for the Hospitalized Child: A Handbook of Inpatient Pediatrics. AAP: 2013: (2016 update accepted) Wolk, R and Fisher ES. Sepsis. In: Caring for the Hospitalized Child, A Handbook of Inpatient Pediatrics (accepted 2015). AWARDS The division continues to receive recognition for teaching and clinical care: Julia Beauchamp-Walters, MD CARES Award, Rady Children s Hospital 2014 Laurie Bernard Stover, MD UCSD Pediatric Housestaff Attending of the Year, 2014 RCHSD Employee of Excellence nominee, 2014 Melissa Cameron, MD CARES Award, Rady Children s Hospital 2015 RESEARCH SUPPORT California Health Care Foundation Planning Grant (PI) 9/2014-4/2015 $50,000 Health Insurers and Palliative Care Providers: New Models of Care California Health Care Foundation Implementation Grant (PI) 9/ $99,900 Payers and Providers: Testing New Payment and Delivery Models for Palliative Care in the Community Pediatric Discharge Program Pedi-BOOST (PI) 9/2011-8/2014 $750,000 University of California Center for Health Quality & Innovation Program (CHQI) Intramural University of California San Diego (PI) 04/ /2015 $48,218 Department /Rady Children s Hospital San Diego competitive grant Interprofessional Team Training in the Pediatric Life Support Program: Effects on Resuscitation Outcomes and Team Skill Development P (PI) 11/2011 7/2014 $87,461 A multicenter, randomized, observer-blinded, active-controlled study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of ceftaroline versus comparator in pediatric subjects with acute bacterial skin and skin structure infections (ABSSSI). P (PI) 11/2012 7/2014 $129,266 A Multicenter, Randomized, Observer Blinded, Active-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Ceftaroline versus Ceftriaxone in Pediatric Subjects with Communityacquired Bacterial Pneumonia Requiring Hospitalization. P (PI) 1/2013-7/2014 $189,011 A Multicenter, Randomized, Observer-Blinded, Active-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Ceftaroline Versus Ceftriaxone Plus Vancomycin in Pediatric Subjects with Complicated Community-acquired Bacterial Pneumonia. 166 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 167

85 Host-Microbe Systems & Therapeutics 168 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 169

86 INTRODUCTION The Division of Host-Microbe Systems & Therapeutics brings together a diverse group of scientists and physicians performing interdisciplinary research to understand the interactions of humans and the microbial world in both health and disease. Fundamental principles of microbiology, immunology, pharmacology, -OMICs (genomics, proteomics, metabolomics, and the human microbiome) and systems biology are brought to bear to understand the pathogenesis of common childhood infectious diseases and inflammatory disorders. This insight inspires innovative discovery programs and translational studies of new drugs and interventions to restore optimal health in childhood and throughout life. FACULTY Our Division is the headquarters of the NIH/NICHD Sponsored Research Program in Developmental Pharmacology (RPDP), NIH/NIAID Funded Program in the Systems Biology of Antimicrobial Resistance, UCSD campus-wide Center for Microbiome Innovation (CMI), and the Collaborative to Halt Antibiotic-Resistant Microbes (CHARM). Division members also interact closely with the UCSD Center for Drug Discovery Innovation (cddi). Our basic and translational research programs in infection biology that provide new insights into the molecular basis of microbial pathogenesis and the function of host immunity, with a focus on exploiting these discoveries for new treatment strategies. Novel therapies are sought from genome-driven high throughput chemical biology screens, systems biology approaches, targeted neutralization of virulence phenotypes, pharmacologic augmentation of host innate immune functions, modulation of host inflammatory responses, reversal of antimicrobial resistance phenotypes and prophylactic vaccines. Victor Nizet, MD Division Chief, Professor & Vice Chair for Basic Research Department, Professor of Pharmacy & Pharmaceutical Sciences Brookie Best, PharmD Professor of Clinical Pharmacy & Pediatrics Associate Dean for Student Affairs, Skaggs School of Pharmacy Edmund Capparelli, PharmD Professor and Clinical Pharmacy Pieter Dorrestein, PhD Professor of Pharmacy, Pharmacology & Pediatrics Kelly Doran, PhD Adjunct Professor Professor of Biology San Diego State University The microbes that normally inhibit our gut, skin and mouth provide 99% of our body s gene content, and function to help us digest and process nutrients, while generating their own waste and metabolites. Importantly, these microbes constantly interact with, and help shape, our immune systems. It is now recognized that the makeup of our microbiome influences diverse diseases including food allergies, obesity, inflammatory bowel disease, colon cancer, rheumatoid arthritis, atherosclerosis, asthma and even the brain function and behavior. Microbial communities we encounter in the home, hospital and outdoor environments further influence our health status. Understanding our microbiome and its role in human health can inspire novel diagnostic, preventative and therapeutic interventions. Indeed, the rich chemical and metabolic diversity of the microbiome is itself a promising source for new drug discovery. The Division has a robust Pharmacometrics Unit, recognized internationally for its leadership in pharmacokinetic and pharmacodynamic modeling, including sparse data collection techniques and population analysis methodologies that enable appropriate dosing in pediatric subpopulations. The UCSD Pharmacometrics Unit leads the NICHD Pediatric Trials Network (PTN) in clinical pharmacology modeling and simulation activities and supports other multi-center and collaborative research projects. The Pediatric Pharmacology Laboratory (PPL), a dynamic working unit with the capability, experience and expertise to analyze quantitatively and qualitatively a large number of drugs in a variety of sample matrices, including many core services for the NIAID/NIH International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) pharmacology program. Headquarters of the NIH/ NICHD Sponsored Research Program in Developmental Pharmacology 170 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report DIVISION FAST FACTS $7.2 Million in Major Research Grants MAJOR PLANS AND GOALS Continue to solidify and expand the research focus of the UCSD Research Program in Developmental Pharmacology (RPDP), part of a NIH/NICHD-sponsored national network, with the focus Pediatric Developmental Pharmacology for Inflammatory and Infectious Diseases in our renewed center grant. Identify and support outstanding young pediatric subspecialty fellows for advanced training in our Division s new NIH/NICHD T32 Training Program Postdoctoral Research Training in Pediatric Clinical Pharmacology and Therapeutics Serve as the academic leadership headquarters for the Center for Microbiome Innovation, to accelerate microbiome research and develop new methods for manipulating microbiomes to improve human health, including development of gnotobiotic mouse models for experimental analysis. Build upon our recent $9.5M NIH U01 Grant on the Systems Biology of Antibiotic Resistance to launch and serve as headquarters for the campus-wide Collaborative to Halt Antibiotic-Resistant Microbes (CHARM), a center for innovative approaches beyond classical antibiotics to combat this most urgent threat to medicine and the public health worldwide. 16 Faculty 75 Postdoctoral Fellows Rob Knight, PhD Professor & Computer Science & Engineering Director, Center for Microbiome Innovation Bernice Aguilar, PhD Mahmoud Al-Bassam, PhD Katie Amato, PhD Amnon Amir, PhD Jenya Antonova, PhD Ericka Anderson, PhD Fatemeh Askarian, PhD Federico Beasley, PhD Amina Bouslamini, PhD Elizabeth Brunk, PhD Ke Chan, PhD Wan-Tien Chiang, Ph.D. Jose Carlos Clemente Litran, PhD Alison Coady, PhD Jason Cole, PhD Ross Corriden, PhD Annie Cowell, MD, MPH Yang Ding, PhD Erika Flannery, PhD Nathan Lewis, PhD Assistant Adjunct Professor Elizabeth Winzeler, PhD Professor Daniela Galzerani, PhD Neha Garg, PhD David Gonzalez, PhD Antonio Gonzalez-Peña, PhD Purva Gupta, PhD Anna Henningham, PhD Alyssa Hobby, PharmD Justin Hoffman, PharmD, MS Andrew Hollands, PhD Embriette Hyde, PhD Gloria Kim, PharmD Jinu Kim, PhD Evguenia Kopylova, PhD Armin Kousha, PhD Monika Kumaraswamy, MD Lisa Lam, PharmD Greg LaMonte, PhD Janet Liu, PhD Anel Lizcano, PhD Bernhard Palsson, PhD Distinguished Professor of Bioengineering and Pediatrics FELLOWS George Sakoulas, MD Associate Adjunct Professor Karsten Zengler, PhD Associate Adjunct Professor Tal Luzzatto Knaan, PhD Jessica Metcalf, PhD Sabine Ottilie, PhD Maulik Patel, PharmD, PhD Doris LaRock, PhD Christopher LaRock, PhD Christian Lauber, PhD Greg LaMonte, PhD Ann En-Ju Lin, PhD Catherine Lozupone, PhD Stephan Meister, PhD Pamela Orjuela-Sanchez, PhD Laura Parfrey, PhD Katy Patras, PhD Vanessa Phelan, PhD Dorota Porazinska, PhD Anne Richelle, Ph.D. Angelica Riestra, PhD Laura Sanchez, PhD Adriana Tremoulet, MD, MAS Associate Professor of Clinical Pediatrics Associate Director, Kawasaki Disease Research Center Jon Sanders, PhD Stephanie Shin, MD Philipp Spahn, PhD Ismael Secundino-Vélasquez, PhD Kensuke Shoji, MD Se Jin Song, PhD Luke Thompson, PhD Sadee Tran, PharmD Chih-Ming Tsai, PhD Anders Valderrama, PhD Nina Van Sorge, PharmD, PhD Tony Walters, PhD Jeremy Watrous, PhD Douglas Woodhams, PhD Melanie Wree, MD Zhenjiang Xu, PhD Masaya Yamaguchi, DDS, PhD Laurence Yang, PhD Daniel Zielinski, PhD Cristal Zuniga, PhD Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 171

87 The Division interacts closely with pediatricians and pediatric subspecialty physicians at Rady Children s Hospital-San Diego (RCHSD) and UCSD through its Clinical Trials Unit, which develops and executes phase I - III trials of new and existing therapeutic agents for pediatric populations. Dr. Tremoulet is the Medical Director of the Pediatric Pharmacology Laboratory. The consultative expertise of Drs. Edmund Capparelli and Brookie Best are provided on issues of therapeutic drug monitoring and HIV pharmacology locally and across the country. Victor Nizet, MD is the mentor of more than a dozen postdoctoral fellows and five graduate students in hist basic research laboratory, and 15 students have completed the PhD degree in his laboratory. He is a Track Leader for Microbiome and Microbial Sciences in the UCSD Biomedical Sciences Graduate Program, Section Leader for the Biomedical Sciences 200 Course (Fall Quarter), Course Director for the Biomedical Sciences course Microbial Pathogenesis & Host Response (BIOM 253), Vice Chair for Basic Research in the Department, a member of the UCSD Graduate Council, and on the Leadership Team of the National Center for Leadership in Academic Medicine, a junior faculty development program. Edmund Capparelli, PharmD teaches pharmacology topics to both pharmacy and medical students in the School of Medicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences. During the past year, Dr. Capparelli delivered lectures and led workshops in Clinical Pharmacology and helped organize and lead the Children s Health and Education Research Symposium (CHERS) for UC San Diego Pediatric Post-docs. He also taught pharmacokineticpharmacodynamic modeling to the NICHD T32 fellows through a live lecture and webinar series and population pharmacokinetic modeling seminar series to post-docs in the UC San Diego Pfizer Clinical Pharmacology Fellowship Program. Brookie M. Best, PharmD, MAS teaches Biopharmaceutics and Clinical Pharmacokinetics and Pharmacodynamics to first-year student pharmacists in the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences. Dr. Best is also Principal Investigator of an NICHD-supported T35 training grant for Predoctoral Student Research in Pediatric and Maternal Pharmacology. Kelly Doran, PhD has supervised excellent postdoctoral fellows, PhD and master's students and undergraduates in her laboratory. She teaches in the UCSD SOM 208 Microbiology laboratory course as well as the BGGN 238B graduate course in Integrative Microbiology and 4 guest lectures (Fall and Winter Quarters) in the course in Bacteriology (BIMM 120) in UCSD Biological Sciences. For the last 5 years, she has lectured and led interactive sessions in the Biomedical Sciences 253 graduate course Pathogens and Host Defense at UCSD and teaches the UCSD Department of Biological Sciences course Integrative Microbiology (BGGN 238B). As part of her primary appointment at San Diego State University, she teaches in several courses: General Microbiology (BIOL 350), Medical Microbiology (BIOL 584) and Seminar in Molecular Biology (MB 600). Pieter Dorrestein, PhD teaches extensively in the curriculums of the School of Medicine, School of Pharmacy and Department 172 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report CLINICAL ACTIVITIES Dr. Adriana Tremoulet attends on the inpatient infectious disease service, as well as the Kawasaki disease service. She also provides follow up for infectious disease and Kawasaki disease patients in the outpatient setting. Dr. George Sakoulas is an adult infectious diseases specialist who provides consultative services on patients with complicated infectious disease conditions and antibiotic resistance problems in the inpatient and outpatient settings. TEACHING ACTIVITIES of Chemistry and Biochemistry. He lectures in the courses on Proteomics, Metabolomics, Mass Spectrometry, Chemistry of Enzyme Catalyzed Reactions, Structural and Quantititative Pharmacology, Biochemical Energetics & Metabolism, and Informatics. He is faculty advisor for 10 PhD students and 6 Master s students Rob Knight, PhD lectures about the microbiome and bioinformatics in a range of courses at the graduate and undergraduate level in the School of Medicine, the Division of Biological Sciences, and the Jacobs School of Engineering, as well as several dozen continuing medical education lectures per year to audiences interested in nutrition, neonatal care, and the microbiome. His online course Gut Check, run through Coursera, has had over 30,000 participants. He also mentors graduate students through the BMS program, and has contributed to many T32 training grants at UCSD. Nathan Lewis, PhD teaches a course on research presentation to graduate students in the Bioinformatics and Systems Biology Ph.D. program. These classes are held weekly throughout the school year. He also serves on the student fellowship committee for the Bioinformatics and Systems biology Ph.D. program. Bernhard Palsson, PhD has extensive mentorship of graduate and postgraduate scholars in the laboratory, and has given cutting edge lectures in Bioengineering for 20 years. He teaches Systems Biology and Bioengineering, consisting of (1) enumeration of biological components participating in a biological process, (2) reconstruction of interactions to form a network, (3) mathematical representation for analysis, interpretation, and prediction, and (4) model validation and use in prospective design. He also teaches Network Reconstruction, covering the process of reconstructing complex biological reaction networks. Reconstruction of metabolic networks, regulatory networks, and signaling networks are also covered, in addition to bottom-up and top-down approaches. The use of collections of historical data, principles underlying highthroughput experimental technologies, and examples given on how this data is used for network reconstruction, consistency checking, and validation are taught. George Sakoulas, MD shares his expertise in clinical therapeutics in a series of lectures in the School of Medicine and Pharmacy curricula on bacteriology, infectious disease pathogenesis and therapeutics, and antibiotic stewardship. He mentors or co-mentors several undergraduate students, PhD candidates and medical fellows in the laboratory, including serving on thesis committees. Adriana H. Tremoulet, MD, in the co-principal Investigator of the NICHD-supported T32 clinical pharmacology fellowship. She also lectures to pharmacy students about pediatric pharmacology as well as to medical students, residents and nurses at RCHSD about Kawasaki disease. Dr. Tremoulet gives inpatient rounds and weekly case conferences on pediatric infectious diseases. Elizabeth Winzeler, PhD has leadership roles in the educational mission of the UCSD Genetic Training Program and the Institute of Genomic Medicine. She lectures on a variety of topics in the UCSD School of Medicine curriculum and its PhD graduate programs. Dr. Winzeler is a commited laboratory mentor whose graduate and post-graduate trainees have been able to obtain independent fellowship support, publish well and to move on to rewarding Victor Nizet, MD leads a basic research laboratory focused on microbial pathogenesis and the innate immune system, with a special focus on invasive bacterial infections and antibiotic resistant pathogens. Using a variety of molecular genetic approaches, the laboratory seeks to discover and characterize bacterial virulence determinants involved in cytotoxicity, adherence, invasion, inflammation, molecular mimicry and resistance to immunologic clearance. In companion studies, we investigate the contribution of host factors such as antimicrobial peptides, leukocyte surface receptors, signal transduction pathways, and transcription factors in defense against invasive bacterial infection. Ultimately, we believe the basic information gained through this platform will lead to novel treatment strategies for infectious diseases, involving targeted neutralization of bacterial virulence phenotypes, pharmacologic augmentation of host phagocytic cell function, targeted antibody based therapeutics, and smarter use of existing antibiotics to maximize synergies with the host immune system. Brookie Best, PharmD, MAS specializes in the clinical pharmacology of antiretroviral agents, with expertise in antiretroviral therapeutic drug monitoring, treatment of HIV-infected pregnant women and children, and antiretroviral central nervous system penetration. She serves as principal investigator or co-investigator on projects with the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT), the California Collaborative Treatment Group (CCTG) and the UCSD HIV Neurobehavioral Research Center (HNRC). Edmund Capparelli, PharmD focuses his research on pharmacokinetic and pharmacodynamic modeling through the division s Pharmacometrics Unit while specializing in pediatric clinical pharmacology and population pharmacokinetic methods. He leads pharmacokinetic research activities within the NICHD Pediatric Trials Network (PTN) Pharmacometric Core, NIAID IMPAACT Network Specialized Pharmacology Laboratory and NICHD supported Center for Research in Pediatric and Developmental Pharmacology (RPDP). His applied knowledge of pharmacometric methods and pediatrics linked with his clinical research expertise is widely recognized, as evidenced by his service to the following groups in this past year: (1) World Health Organization (WHO) Pediatric Antiretroviral Working Group; (2) Pediatric Antiretroviral Guidelines Working Group, US Department of Health and Human Services; (3); Drug for Neglected Disease initiative (DNDi](4) FDA Clinical Pharmacology Advisory Committee (5) NIAID and NICHD special emphasis review panels in HIV and (6) is on the Organizing Committee for the Annual International Pediatric HIV Workshop. Kelly Doran, PhD has a joint appointment in the division and is a Professor of Biology at San Diego State University. Her research focuses on the pathogenesis of neonatal meningitis, with examination of the mechanisms by which certain bacteria can enter the central nervous system and the inflammatory response of the blood-brain positions. I am also am active in the Biomedical Sciences program at the medical school and attend student-oriented functions and retreats as needed. She also helps organizing the Genetics seminar series and the Genetics Training Program annual retreat. Karsten Zengler, PhD has excellent experience in teaching in didactic and interactive format courses at UCSD, and in mentorship of postdoctoral fellows, graduate students and undergraduate trainees in the laboratory, including serving several times as Doctoral Research Advisor and/or Thesis Committee Chair. He has helped develop curriculums and lecture in classes in the UCSD Department of Bioengineering, including the fundamentals of microbial ecology and the microbiome. RESEARCH ACTIVITIES barrier to infection. Through these studies, she seeks to inform novel strategies for treatment and prevention of these potentially life-threatening infections. The laboratory also studies the dynamics of vaginal colonization with the leading neonatal bacterial pathogen group B Streptococcus, to understand how the organism interacts with host epithelium, and persists in the presence of normal microflora, host mucosal defenses and the female menstrual cycle. Pieter Dorrestein, PhD seeks to develop new mass spectrometry based methods to link biological, including disease and health phenotypes to the underlying chemistry and genotypes. In short, we develop tools that translate the chemical language between cells. This research requires the understanding of (microbial) genomics, proteomics, imaging mass spectrometry, genome mining, enzymology, small molecules structure elucidation, bioactivity screening and an understanding of small molecule structure elucidation methods. These tools are used to defining the spatial distribution of natural products in 2D, 3D and in some cases real-time. In addition to the characterization of metabolic exchange the lab aims to characterize transient post-translational modifications and their function in biology. The Collaborative mass Spectrometry Innovation Center will have a focus on the analysis of microbiome metabolism. Areas of recent research directions are microbe-microbe, microbe-immune cells, microbe-host, stem cell-cancer cell interactions and diseased vs. non-disease model organisms and the development of strategies for mass spectrometry based genome mining and to detect and structurally characterize specialized metabolites through crowd source annotation of molecular information. Rob Knight, PhD has a primary appointment in the division, a secondary appointment in the Department of Computer Science & Engineering in the Jacobs School of Engineering, and directs the Center for Microbiome Innovation and co-directs the Chancellor s Initiative in the Microbiome and Microbial Sciences. His laboratory focuses on laboratory and computational methods for high-throughput characterization of human and environmental microbiomes, with specific applications in obesity, inflammatory bowel disease, forensics, and several other topics. He co-founded the Earth Microbiome Project and the American Gut Project, both of which are primarily run from his laboratory at UCSD. A key direction for his laboratory at present is integrating microbiome, metabolic and immunological parameters into systems-level indicators and models that can be integrated with clinical records and make these highly multivariate datasets accessible and understandable to clinicians on timescales relevant to treatment decisions. Nathan Lewis, PhD performs research leveraging genomics and systems biology for drug development, neonatal health, and to unravel complex mechanisms underlying pathophysiology. Specifically, he is leading a collaborative project in which they have sequenced the Chinese hamster genome and are now using that to engineer Chinese hamster ovary (CHO) cell lines to improve the safety, efficacy, Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 173

88 and affordability of recombinant protein drugs. The computational tools are also being deployed to study human milk oligosaccharide synthesis and to associate the oligosaccharides with infant diseases such as necrotizing enterocolitis. He is also using CRISPR-based strategies to unravel the mechanisms underlying glycosylation and proliferation in cancer. Lastly his group is leveraging systems biolgy approaches to develop diagnostic and prognostic biomarkers for autism spectrum disorders. Bernhard Palsson, PhD is the leader of the Systems Biology Research Group that focuses on system-level analysis of the multigeneic processes that control cellular functions. Palsson's group views the coordinated action of multiple gene products as a network or a socalled genetic circuit. His current research efforts focus on genetic circuits involving metabolism and gene regulation. Metabolism is the "chemical engine" that drives the living process. Together, the enzymes used in metabolism produce all of the major constituents of the cell. Combining powerful systems science analysis techniques with the tools of bioinformatics, the group has developed methods that use the metabolic genotype of an organism to analyze, interpret, and predict its metabolic phenotype under particular conditions. He has further developed in silico models for the human red blood cell, E.coli, H.influenza, H.pylori, MRSA and S.cerevisae. Using these in silico strains he can study variations in the genotype and shifts in metabolic routing resulting from changing growth conditions, adaptive evolution or genetic deletions. George Sakoulas, MD performs translational and clinical research on the treatment of Gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). He has been able to translate pharmacodynamic interactions observed with antibiotics in the laboratory into successful treatments for patients with refractory infections, utilizing novel combination therapies. His current efforts examine host characteristics and biomarkers that can predict clinical outcome as a method of risk stratification and selection of antibiotics, as well as studying the pharmacodynamic interaction between host innate immunity and administered antibiotics. Adriana H. Tremoulet, MD, MAS is the Associate Director of the Kawasaki Disease (KD) Research Center. Her research has concentrated on developing a diagnostic test for KD, the most common cause of acquired heart disease in children, as well as repurposing and assessing the safety and pharmacokinetics of new therapies for KD. She led the FDA Orphan Drug Grant funded Phase III clinical trial evaluating the use of infliximab in primary treatment of Kawasaki disease. She is the lead PI of two multi-center Phase I/IIa clinical trials of atorvastatin and anakinra in order to evaluate these medications in children with KD and coronary artery damage. Dr. Tremoulet is the site PI of a study of the Pediatric Trials Network to study the pharmacokinetics of understudied drugs used in pediatrics, and conducts research on the pharmacokinetics of ampicillin. Elizabeth Winzeler, PhD lead a research program developing innovative ways to treat and diagnose tropical diseases with a long-term interest in promoting development and reducing poverty. Most of her efforts are focused on malaria; a disease affecting million people annually she is developing genome-wide methods for discovering and tracking genes conferring resistance to drugs with antimalarial activity. For example, her group is studying the genomes of drug resistant and drug sensitive malaria parasites from the Peruvian Amazon with the goal of finding the genetic determinants of drug resistance. The laboratory is also involved in discovering how thousand of chemical inhibitors with antimalarial activity are working to kill the parasites with a goal of discovering chemically validated targets and chemical tool compounds. Additionally, they are playing a role in public-private partnerships to develop new drugs to treat malaria. Finally, she is using somatic cell and host genetics to investigate host pathogen interactions. The Winzeler laboraotry efforts involve chemical and traditional genetics, genomics, high-content imaging, screening and a network of national and international collaborators interested in public health. Karsten Zengler, PhD focuses his research on microbe/microbe and microbe/host interactions integrating multi-omics data by deploying systems biology approaches. The lab focusses strongly on mechanistic understanding of interactions microorganisms engage in. For this, the laboratory has developed ultra-low input methods for metagenomics and metatranscriptomic to accommodate data generation from miniscule amounts of samples from skin, gut, or the environment. The lab has also pioneered high-throughput cultivation for the isolation and recovery of previously unculturable microorganisms and used this method to access the human skin microbiome. RESEARCH SUPPORT Victor Nizet 1 R01 AI (PI) 04/01/ /31/2017 $2,465,000 NIH (NIAID) Boosting Innate Immunity via HIF to Treat Antibiotic-Resistant Infections HL (Proj Leader) 07/01/ /31/2018 $1,890,000 NIH (NHLBI) Microbial Glycan Mimicry and Glycosidases in Inflammatory Responses R01 AI (Co-PI) 07/01/ /30/2016 $1,250,000 NIH (NIAID) Mechanisms of the M protein in group A Streptococcus virulence R01 AI (PI) 09/01/ /31/2020 $1,430,000 NIH (NIAID) GAS Switch from Colonizing Bacterium to Invasive Pathogen AR (Co-PI) 2/01/ /31/2016 $1,250,000 NIH (NIAMS) Proteolysis and Skin Antimicrobials U54 HD (Co-PI) 09/26/ /30/2016 $2,500,000 NIH (NICHD) Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy U54 AI (Project Leader) 03/01/ /28/14 $800,000 NIH (NIAID) Optimizing Phagocyte Activity Against Antibiotic Resistant Pathgens R01 AI (Co-PI) 12/01/ /30/2017 $1,250,000 NIH (NIAID) Cathelicidins in skin immunity 5 R01 HL (Co-PI) 02/04/ /31/2020 $1,250,000 NIH (NIAID) Glycoprotein Remodeling in Vasculopathy and Coagulopathy of Sepsis R01GM (Co-I) 08/18/ /31/2019 $39,500 NIH (NIGMS) Perturbation of Core Processes Triggers Host Defense vs. Pathogens 5 R01 AI (Co-PI) 4/1/2014-3/31/2019 $75,294 NIH (NIAID) 174 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 175

89 RESEARCH SUPPORT, continued Analyzing a Novel Mechanism of Bacterial camp-producing Toxins Brookie M. Best, PharmD UM1 AI (P.I. of Sub) 06/01/ /30/2016 $984,015 NIH/NIAID Pilot Pharmacokinetic Study of Psychiatric Medications in Children 5 UM1 AI (Co-I) 01/01/ /30/2020 $2,823,246 NIH/NIAID Laboratory Center IMPAACT Leadership Group U54 HD (Co-I) 09/26/ /30/2016 $3,734,148 NIH/NICHD Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy 5 T35 HD S1 (P.I.) 04/01/ /31/2016 $36,612 NIH/NICHD Predoctoral Research Training in Maternal and Pediatric Pharmacology 5 T35 HD (P.I.) 04/01/ /31/2015 $172,764 NIH/NICHD Predoctoral Research Training in Maternal and Pediatric Pharmacology 5 P30 MH (Co-I) 04/01/ /31/2016 $1,777,614 NIH/NIMH HIV Neurobehavioral Research Center Pharmacology Core 1 R01 HD (Co-I) 04/01/ /31/2019 $311,856 NIH/NICHD Phase I and IIa trial of atorvastatin in children with acute Kawasaki disease Industry Grant (Co-I) 02/01/ /31/2025 $20,008 Pfizer Lipitor in infants and children with coronary artery abnormalities in acute Kawasaki disease Intra-/Extramural Grant (Co-I) 09/01/ /31/2014 $270,000 NIH Clinical Center Inflammation and Function of P-gp in HIV Infection of Brain University of California (Co-I) 04/01/ /31/2016 $7,091,600 CHRP Epidemic Interventions Demonstration Project Research Award: ALERT Projects, CCTG 593, 594, 595, 596 Contract (Co-I) 09/01/ /31/2014 $642,719 NIH/NCCAM Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin Edmund Capparelli, PharmD U54 HD (P.I) 09/26/ /30/2016 $3,734,148 NICHD Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy (Co-I) 09/29/ /27/2014 $22,643 (sub-only) NIH/Duke University Sedation, Status Epilepticus Lab Re-Analysis (Co-I) 06/15/ /14/2014 $145,041 (sub only) NIH/Duke University Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care (Co-I) 07/06/ /14/2013 $38,191 (sub only) NIH/Duke Midazolam use in Status Epileticus (Co-I) 09/30/ /29/2015 $27,857 (sub only)nih/duke Pediatric Trials Network Leadership Committee Kelly Doran, Ph.D. R01 NS (P.I) 07/01/ /31/2016 $1,009,090 NIH/NINDS Blood-Brain Barrier Failure during Bacterial Meningitis Joint Venture Prog (P.I.) 07/01/ /31/2013 $25,000 CSUPERB Characterization of a novel peptide to treat bacterial infection (PI subcontract) 08/01/12 07/31/16 $393,988 UCSD (NIH) Institutional Research & Academic Career Development Award U54CA (co-pi) 05/01/ /31/2013 $100,000 NIH/NCI, Analysis of Oral Microbiota in Human Subjects R01 AI (co-i) 07/01/14 06/30/19 $11,213 NIH/ NIAID Role of an ornithine rhamnolipid pigment in GBS virulence Pieter Dorrestein, PhD R01GM A1 (PI) 4/1/12-2/29/17 $320,000 NIH/NIGMS Experiment based genome mining of ribosomal natural products R01GM (Co-PI) 7/1/13 6/30/17 $284,305 NIH/NIGMS Mapping the secondary metabolome of marine cyanobacteria IOS (PI Subaward) 8/1/14-7/31/17 $118,842 NSF Defining the Organizational Principles of Microbial Communities Colonizing Plant Roots R01HL (Consortium PI) 7/1/14-6/30/16 $32,295 NIH/NHLBI Microbiome Acquisition and the Progression of Inflammation and Airway Disease in Infants with Cystic Fibrosis (PI) 12/1/14-11/30/16 $40,554 Bayer Cropscience NanoDESI to Characterize Metabolome of Bacillus Species in Soil G (Co-PI) 4/1/15-3/31/16 $217,391 Alfred P. Sloan Foundation Integrated data platform for built environment microbes and metabolites (PI) 5/18/15-5/17/18 $129,032 Janssen Research Mass Spectrometry Based Metabolomics and Molecular/Drug Tissue Imaging, Part A: Diagnosing Diseases through Human Skin n (Consortium PI) 7/1/15-6/30/ (sub PI) 1/1/ /31/2014 $450,000 ALFRED P. SLOAN FOUNDATION MoBe DAC-- A data analysis core for the Indoor Environment Microbiology Program B (co-pi) 10/1/12-1/1/15 $115,000 UNIVERSITY OF CHICAGO MoBe DAC: A Data Analysis Core for the Indoor Environment Microbiology HHMI Early Career Scientist 9/1/09-3/31/15 $1,500,000 Studies of the Human Microbiome WU /OPP (sub PI) 11/1/11 3/31/2015 $1,239,360 GATES FOUNDATION Breast Milk, Gut Microbiome and Immunity (BMMI) Project 1 S10 OD (PI) 4/22/2013-4/22/2015 $1,900,000 NIH OD A High-memory Supercomputer for Proteomics, Text Mining and Microbiome Research U01 HG (co-pi) 5/1/2013-4/30/2015 $138,128 University of Maryland NIH Open Data Framework (OSDF): Support Infrastructure for Next Generation Sequence Data Storage, Analysis and Management DT (PI) 7/1/2013 6/30/2015 $1,000,000 Keck Foundation The Earth Microbiome Project 14-A (co-pi) 5/1/2014-6/30/2015 $90,499 AP Sloan Foundation Microbiomes of Homes Across Cultures HHSN C (co-pi) 1/1/2015 7/31/2015 $431,372 PPD VACCINES Oral Microbiome in NHANES Testing HHSN C (co-pi) 1/1/2015 7/31/2015 $26,164 PPD VACCINES Fecal and Saliva Stability (co-pi) 10/1/2011-9/30/2015 $57,504 BSF - United States-Israel An integrated computational and experimental investigation of microbial communities in the human gut MSN (co-pi) 2/14/2013-3/1/2016 $155,447 Moore Foundation Tracking microbial habitat transitions using single-cell transcriptomics (PI) 9/1/2013-8/31/2016 $977,501 Templeton Convergent Evolution of the Vertebrate Microbiome 1U54DE (co-pi) 9/6/2013-8/31/2016 $75,000 NIH/Harvard Characterizing the gut microbial ecosystem for diagnosis and therapy in IBD (PI) 4/1/2014 4/1/2016 $1,000,000 SLOAN FOUNDATION An integrated data platform for democratized sequencing Ludwig Maximilian U. Munchen (PI) 1/1/2015-6/30/2016 $150,000 GABRIEL study: Potential effects of microorganisms on asthma P01DK (co-pi) 1/1/2015 6/30/2019 $104,021 Washington Univ. St Louis Metagenomic Studies of the Gut Microbiomes of Obese and Lean Twins, Core B and Project 3 U19AI (co-pi) 1/1/2015-7/31/2019 $58,523 Oak Crest Institute of Science Integrated Preclinical/Clinical Program for HIV Microbicides and Biomedical Prevention (IPCP-MBP) 2014-R2-CX-K411 (PI) 1/1/ /31/2016 $637,941 DEPARTMENT OF JUSTICE Evaluating the Skin Microbiome as Trace Evidence (PI) 04/10/15-04/09/16 $151,087 LAUREATE INSTITUTE T-1000: Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders G (PI) 04/01/ /31/2016 $284,087 SLOAN FOUNDATION An integrated data platform for built environment microbes and metabolites CA 1072-A-7 (co-pi) 04/01/ /31/2016 $2,555 UCSF/Multiple Sclerosis Society The MS Microbiome Constortium (MSMC): an academic multi-disciplinary collaborative effort to elucidate the role of gut microbiota in MS Bernhard Palsson, PhD 89695A 06/01/11-12/31/20 $3,796,969 Novo Nordisk Foundation Network Reconstitution and in Silico Biology for NNFCB 8558BA 06/01/13-12/31/21 $3,796,969 Novo Nordisk Foundation Network Reconstruction in Silico for CHO Chinese Hamster Ovary DE-SC /01/12-08/31/17 $2,598,000 JCVI/DOE Optimization of Energy Flow Through Synthetic Metabolic Modules and regulatory Networks in a Model Photosynthetic Eukaryotic Microbe /15/12-09/14-17 $409,612 DOE/Stanford Multi-Scale Molecular Systems Biology: Reconstruction and Model Optimization DE-AC05-76RL /15/08-09/14/13 $917,395 NIAID / PNNL / DOE A Systems Biology Program for Pathogenic Enterobacteriaceae DE-PS02-09ER /01/10-06/30/13 $767,340 DOE / Univ. of Massachusetts Biological Systems Research on the Role of Microbial Communities in Carbon Cycling DE-SC /15/10-08/14/13 $893,001 DOE A Systems Biology Knowledgebase: Context for Content R01 GM /01/11-04/30/15 $1,088,000 NIH/NIGMS Genome-Scale in Silico Model for E. Coli R01 GM /01/11-06/30/14 $831,972 NIH/NIGMS 176 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 177

90 Model-Guided Identification of Synthetic Lethal Genes for Drug Target Development Adriana Tremoulet, MD, MAS 1R01HD (PI) 09/23/ /30/2018 $791,069 NIH/NICHD Phase I/IIa trial of atorvastatin for children with acute Kawasaki disease T32HD (co-pi) 07/01/ /30/2021 $60,470 NIH/NICHD Developing Pediatric Clinical Pharmacologists for the Advancement of Therapeutics Challenge Grant (co-i) 07/01/ /30/2020 $2,500,000 Macklin Foundation Comprehensive funding for Kawasaki Disease research 5U54HD (co-pi) 09/26/ /30/2016 $488,000 NICHD Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy HHSN I (co-i) 06/25/ /24/2017 NIH/Duke Developing pharmacokinetic and pharmacodynamics models for selected drugs in the Pediatric Trials Network Clinical Research (PI) 05/01/ /30/201 $17,795 UCSD Pediatrics Grant Immunomodulatory Effects of Anakinra in Children with Acute KD and Coronary Artery Abnormalities Rady Children s Hospital (PI) 05/01/ /30/2015 $50,000 Academic Enrichment Anakinra in Infants and Children with Coronary Artery Abnormalities in Acute Kawasaki Disease George Sakoulas, MD U54 HD (co-i) 09/26/ /30/2016 $450,000 NIH (NICHD) Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy 5R21AI (co-i) 03/01/14-02/28/17 $75,000 NIH/NIAID Validation and development of trans-translation as a drug target for MRSA Sponsored Research (PI) 06/01/ /31/2015 $40,000 Forrest Pharmaceuticals Proteomic and transcriptional changes in MRSA induced by sub-lethal concentrations of nafcillin and ceftaroline Elizabeth Winzeler, PhD R01AI (P.I.) 08/14/ /31/2017 $2,048,124 NIH/NIAID Defining the targets of broad intervention antimalarial agents OPP (P.I.) 03/23/2012-6/30/2016 $1,463,767 Gates Foundation Designing a high-throughput malaria sexual development assay OPP (P.I.) 03/23/ /31/2016 $1,454,543 Gates Foundation Target Discovery for Antimalarials R01AI (P.I.) 05/01/ /30/2015 $1,000,000 NIH/NIAID Discovery of chemically validated malaria liver stage targets MMV12/0094, (P.I.) 05/01/ /31/16 $911,807 Medicines for Malaria Venture Malaria Liver Stage Assays for Drug Discovery NITD/13/RCA/001RO (P.I.) 07/01/ /31/2014 $244,136 Novartis Inst.for Trop. Dis. Discovery of novel inhibitors of liver-stage Plasmodium species and complementary mechanism of action studies P50 GM (co-pi) 09/18/10-05/31/19 $407,000 NIH (NIGMS) Center for Systems Biology of Cellular Stress Responses Karsten Zengler, PhD DE-SC (PI) 09/01/ /31/2017 $1,352,989 Department of Energy Next Gen3: Sequencing, Modeling, and Advanced Biofuels 2P50AA (PI) 01/01/ /31/2014 $31,000 Center for ALPD and Cirrhosis The Role of the Microbiome in Alcoholic Liver Disease. What Factors Contribute to Dysbiosis of the Microbiome inalcoholic Liver Disease? 2P50AA (PI) 01/01/ /31/2015 $27,900 Center for ALPD and Cirrhosis The Role of the Microbiome in Alcoholic Liver Disease UCSD (PI) 02/01/ /30/2016 $25,000 FISP Examining the Role of the Microbiome in Alcoholic Liver Disease through Systems Biology NZBNA# (PI) 05/01/15-04/30/16 $38,750 Novozymes Biologicals Transcriptional Response of Bacillus During Application on Human Skin DE-SC (Co-PI) 09/01/ /31/2017 $299,257 (sub only) Department of Energy Systems Biology of Autotrophic-Heterotrophic Symbionts for Bioenergy R21 AR (Co-PI) 07/01/ /30/201 $77,500 (sub only) NIH (R21) Establishing a Skin Microbiome Transplant PUBLICATIONS Abdel-Haleem, A.M., Abuelela, A.F, Solovyev, V., Jamshidi, N., Lewis, N.E. Model-Driven Analysis of Gene Expression Data: Application to Metabolic Re-programming during T-cell Activation. BioComp 2015; Agarwal V, Diethelm S, Ray L, Garg N, Awakawa T, Dorrestein PC, Moore BS. Chemoenzymatic Synthesis of Acyl Coenzyme A Substrates Enables in Situ Labeling of Small Molecules and Proteins. Org Lett. 2015;17: Ali SR, Fong J, Carlin AF, Busch TD, Linden R, Angata T, Areschoug T, Parast M, Varki N, Murray J, Nizet V, Varki A. Siglec-5 and -14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus. J Exp Med 2014; 211: Ali SR, Karin M, Nizet V. Signaling cascades and inflammasome activation in microbial infections. Inflammasome 2015; 2:7 12. Alderete TL, Autran C, Brekke BE, Knight R, Bode L, Goran MI, Fields DA. Associations between human milk oligosaccharides and infant body composition in the first 6 mo of life. Am J Clin Nutr. 2015; 102: Amato K R, Yeoman C J, Cerda G, A Schmitt C, Cramer J D, Miller ME, Gomez A, R Turner T, Wilson BA, Stumpf RM, Nelson KE, White BA, Knight R, Leigh SR. Variable responses of human and non-human primate gut microbiomes to a Western diet. Microbiome. 2015;3:53. Anderson EL, Cole JN, Olson J, Ryba B, Ghosh P, Nizet V. The fibrinogen-binding M1 protein reduces pharyngeal cell adherence and colonization phenotypes of M1T1 group A Streptococcus. J Biol Chem 2014; 289: Andrade RM, Chaparro JD, Capparelli E, Reed SL. Auranofin is highly efficacious against Toxoplasma gondii in vitro and in an in vivo experimental model of acute rtoxoplasmosis. PLoS Negl Trop Dis Jul 31;8:e2973. Angata T, Ishii T, Motegi T, Oka R, Taylor RE, Campos-Soto P, Chang YC Secundino I, Gao CX, Ohtsubo K, Kitazumi S, Nizet V, Varki A, Gemma A, Kida K, Taniguchi N. Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cell Mol Life Sci 2013; 70: Ansong C, Deatherage BL, Hyduke D, Schmidt B, McDermott JE, Jones MB, ChauhanS, Charusanti P, Kim YM, Nakayasu ES, Li J, Kidwai A, Niemann G, Brown RN, McAteer K, Heffron F, Peterson SN, Motin V, Palsson BØ, Smith RD, Adkins JN. Studying Salmonellae and Yersiniae host-pathogen interactions using integrated 'omics and modeling. Curr Top Microbiol Immunol. 2013;363: Askarian F, van Sorge NM, Sangvika M, Beasley FC, Henriksend JR, Sollida JU, van Strijp J, Nizet V, Johannessen M. A Staphylococcus aureus TIR-domain protein virulence factor blocks TLR2-mediated NF-κB signaling. J Innate Immun 2014; 6: Aurich MK, Paglia G, Rolfsson Ó, Hrafnsdóttir S, Magnúsdóttir M, Stefaniak MM, Palsson BØ, Fleming RM, Thiele I. Prediction of intracellular metabolic states from extracellular metabolomic data. Metabolomics. 2015; 11: Autmizguine J, Moran C, Gonzalez D, Capparelli EV, Smith PB, Grant GA, Benjamin DK Jr, Cohen-Wolkowiez M, Watt KM. Vancomycin cerebrospinal fluid pharmacokinetics in children with cerebral ventricular shunt onfections. Pediatr Infect Dis J. 2014; 33:e270-2 Awakawa T, Cru semann M, Munguia J, Ziemer N, Nizet V, Moore BS. Salinipyrone and pacificanone are biosynthetic byproducts of the rosamicin polyketide synthase. ChemBioChem 2015; 16: Aweeka FT, Hu C, Huang L, Best BM, Stek A, Lizak P, Burchett SK, Read J, Watts H, Mirochnick M, Capparelli EV and IMPAACT P1026s Team. Alteration in cytochrome P450 3A4 activity in HIV-1 infected pregnant women and relationship to antiretroviral pharmacokinetics. HIV Med. 2015; 16: Aziz RK, Monk JM, Lewis RM, In Loh S, Mishra A, Abhay Nagle A, Satyanarayana C, Dhakshinamoorthy S, Luche M, Kitchen DB, Andrews KA, Fong NL, Li HJ, Palsson BØ, Charusanti P. Systems biology-guided identification of synthetic lethal gene pairs and its potential use to discover antibiotic combinations. Sci Rep 2014; 5: Aziz RK, Khaw VL, Monk JM, Brunk E, Lewis R, Loh SI, Mishra A, Nagle AA, Satyanarayana C, Dhakshinamoorthy S, Luche M, Kitchen DB, Andrews KA, Palsson BØ, Charusanti P. 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J Anal Toxicol. 2014; 38: Barber K, Werth B, Ireland C, Stone N, Nonejuie P, Sakoulas G, Pogliano J, Rybak M. Potent synergy of ceftobiprole plus daptomycin against multiple strains of Staphylococcus aureus with varying resistance phenotypes. J Antimicrob Chemother 2014; 69: Barber KE, Rybak MJ, Sakoulas G. Vancomycin plus ceftaroline shows potent in vitro synergy and was successfully utilized to clear persistent daptomycin non-susceptible methicillin-resistant Staphylococcus aureus bacteremia. J Antimicrob Chemother 2014; 70: Barber K, Werth B, Ireland C, Stone N, Nonejuie P, Sakoulas G, Pogliano J, Rybak M. Potent synergy of ceftobiprole plus daptomycin against multiple strains of Staphylococcus aureus with varying resistance phenotypes. J Antimicrob Chemother 2014; 69: Barber KE, Rybak MJ, Sakoulas G. Vancomycin plus ceftaroline shows potent in vitro synergy and was successfully utilized to clear persistent daptomycin non-susceptible methicillin-resistant Staphylococcus aureus bacteremia. J Antimicrob Chemother 2014; 70: Barnett TC, Liebl D, Seymour LM, Gillen CM, Lim JY, LaRock CN, Davies MR, Shulz BL, Nizet V, Teasdale RD, Walker MJ. The group A Streptococcus M1T1 clone evades autophagy for intracellular replication. Cell Host Microbe 2013; 14: Barnett T, Cole JN, Rivera Hernandez T, Henningham A, Paton J, Nizet V, Walker MJ. Streptococcal toxins: role in pathogenesis and disease. Cell Microbiol 2015; 17: Barr JJ, Auro R, Furlan M, Whiteson KL, Erb ML, Pogliano J, Stotland A, Wolkowicz R, Cutting AS, Doran KS, Salamon P, Youle M, Rohwer F. Bacteriophage adhering to mucus provide a non-hostderived immunity. 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91 Berti AE, Sakoulas G, Nizet V, Rose WE. β-lactam antibiotics targeting PBP1 selectively enhance daptomycin activity against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2013; 57: Berti AD, Baines SL, Howden BP, Sakoulas G, Nizet V, Proctor RA, Rose WE. Heterogeneity of genetic pathways toward daptomycin nonsusceptibility in Staphylococcus aureus determined by adjunctive antibiotics. Antimicrob Agents Chemother 2015; 59: Bertin MJ, Schwartz SL, Lee J, Korobeynikov A, Dorrestein PC, Gerwick L, Gerwick WH. Spongosine production by a Vibrio harveyi strain associated with the sponge Tectitethya crypta. J Nat Prod. 20; 78: Best BM, Burchett SK, Li H, Stek A, Hu C, Wang J, Hawkins E, Byroads M, Watts DH, Smith E, Fletcher CV, Capparelli EV, Mirochnick M, P1026s Team. Pharmacokinetics of tenofovir during pregnancy and postpartum. HIV Med. 2015; 16: Bhandari T, Olson J, Johnson RS, Nizet V. 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92 Cavaco CK, Patras KA, Zlamal JE, Thoman ML, Morgan EL, Sanderson SD, Doran KS. A novel C5a-derived immunobiotic peptide reduces Streptococcus agalactiae colonization through targeted bacterial killing. Antimicrob Agents Chemother. 2013; 57: Chang J, Li C, Hollenbeck T, Tuntland T, Zeeman AM, Kocken CH, McNamara C, Kato N, Winzeler EA, Yeung BK, Diagana TT, Smith PW, Roland J. Lead optimization of imidazopyrazines: a new class of antimalarial with activity on Plasmodium liver stages. ACS Med Chem Lett. 2014; 5: Chang RL, Xie L, Bourne PE, Palsson BØ. Antibacterial mechanisms identified through structural systems pharmacology. BMC Syst Biol. 2013; 7:102. Chang RL, Andrews K, Kim D, Li Z, Godzik A, Palsson BØ. Structural systems biology evaluation of metabolic thermotolerance in Escherichia coli. Science. 2013; 340: Chang YC, Olson J, Beasley FC, Tung C, Zhang J, Crocker PR, Varki A, Nizet V. 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Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 2014; 588: / Wang NY, Patras KA, Seo HS, Cavaco CK, Rösler B, Neely MN, Sullam PM, Doran KS. Group B streptococcal serine-rich repeat proteins promote interaction with fibrinogen and vaginal colonization. J Infect Dis. 2014; 210: Watrous J, Roach P, Heath B, Alexandrov T, Laskin J, Dorrestein PC. Metabolic profiling directly from the Petri dish using nanospray desorption electrospray ionization imaging mass spectrometry. Anal Chem 2013; 85: Watrous JD, Phelan VV, Hsu CC, Moree WJ, Duggan BM, Alexandrov T, Dorrestein PC. Microbial metabolic exchange in 3D. ISME J 2013; 7: Watt KW, Gonzalez D, Benjamin DK Jr, Brouwer KL, Wade KC, Capparelli E, Barrett J, Cohen-Wolkowiez M. Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive candidiasis in children supported with extracorporeal membrane oxygenation. Antimicrob Agents Chemother 2015; 59: Watts DH, Stek A, Best BM, Wang J, Capparelli EV, Cressey TR, Aweeka F, Lizak P, Kreitchmann R, Burchett SK, Shapiro DE, Hawkins E, Smith E, Mirochnick M, IMPAACT P1026s Study Team. Raltegravir pharmacokinetics during pregnancy. J Acquir Immune Defic Syndr. 2014; 67: Weingarden A, González A, Vázquez-Baeza Y, Weiss S, Humphry G, Berg-Lyons D, Knights D, Unno T, Bobr A, Kang J, Khoruts A, Knight R, Sadowsky MJ. Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection. Microbiome 2015; 3:10. Weiss S, Amir A, Hyde ER, Metcalf JL, Song SJ, Knight R. Tracking down the sources of experimental contamination in microbiome studies. Genome Biol 2014; 15:564. Werth BJ, Barber KE, Tran KN, Nonejuie P, Sakoulas G, Pogliano J, Mybak MJ. Ceftobiprole and ampicillin increase daptomycin susceptibility of daptomycin-susceptble and resistant VRE. J Antimicrob Chemother 2014; 70 (2): Werth B, Steed M, Ireland C, Tran T, Nonejuie P, Murray B, Rose W, Sakoulas G, Pogliano J, Arias C, Rybak MJ. Defining daptomycin resistance prevention exposures in vancomycin-resistant Enterococcus (VRE) faecium and E. faecalis. Antimicrob Agents Chemother 2014; 58(9): Wilkinson DS, Shah J, Ericka Anderson EL, Mitra K, Meisenhelder J, Chang JT, Ideker T, Hunter T, Nizet V, Dillin A, Hansen M. Phosphorylation of LC3 by the sterile-20 kinases STK3/STK4 is essential for autophagy. Mol Cell 2015; 57: Winnikoff JR, Glukhov E, Watrous J, Dorrestein PC, Gerwick WH. Quantitative molecular networking to profile marine cyanobacterial metabolomes. J Antibiot 2014; 67: Winzeler EA, Manary MJ. Drug resistance genomics of the antimalarial drug artemisinin. Genome Biol 2014;15(:544. Woodhams DC, Brandt H, Baumgartner S, Kielgast J, Ku pfer E, Tobler U, Davis LR, Schmidt BR, Bel C, Hodel S, Knight R, McKenzie V. Interacting symbionts and immunity in the amphibian skin mucosome predict disease risk and probiotic effectiveness. PLoS One 2014; 9:e Wu W, Jamshidi N, Eraly SA, Liu HC, Bush KT, Palsson BØ, Nigam SK. Multispecific drug transporter Slc22a8 (Oat3) regulates multiple metabolic and signaling pathways. Drug Metab Dispos 2013; 41: Xu Z, Malmer D, Langille MG, Way SF, Knight R. Which is more important for classifying microbial communities: who's there or what they can do? ISME J. 2014; 8: Xu D, Olson J, Cole JN, van Wijk XM, Brinkmann V, Zychlinsky A, Nizet V, Esko JD, Chang YC. Heparan sulfate modulates neutrophil and endothelial function in antibacterial innate immunity. Infect Immun 2015; 83: Yamaguchi M, Terao Y, Mori-Yamaguchi Y, Domon H, Sakaue Y, Yagi T, Nishino K, Yamaguchi A, Nizet V, Kawabata S. Streptococcus pneumoniae invades erythrocytes and utilizes them to evade human innate immunity. PLoS One 2013; 8:e Yamanaka K, Reynolds KA, Kersten RD, Ryan KS, Gonzalez DJ, Nizet V, Dorrestein PC, Moore BS. Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A. Proc Natl Acad Sci USA 2014; 111: Yang SJ, Mishra N, Sakoulas G, Nonejuie P, Nast C, Pogliano J, Chen KT, Ellison S, Yeaman MR, Bayer AS. Heterogeneity of mprf sequences in methicillin-resistant Staphylococcus aureus clinical isolates: role in cross-resistance between daptomycin and host defense antimicrobial peptides. Antimicrob Agents Chemother 2014; 58 (12): Yang JY, Sanchez LM, Rath CM, Liu X, Boudreau PD, Bruns N, Glukhov E, Wodtke A, de Felicio R, Fenner A, Wong WR, Linington RG, Zhang L, Debonsi HM, Gerwick WH, Dorrestein PC. Molecular networking as a dereplication strategy. J Nat Prod 2013; 76: Yang L, Tan J, O'Brien EJ, Monk JM, Kim D, Li HJ, Charusanti P, Ebrahim A, Lloyd CJ, Yurkovich JT, Du B, Dräger A, Thomas A, Sun Y, Saunders MA, Palsson BØ. Systems biology definition of the core proteome of metabolism and expression is consistent with highthroughput data. Proc Natl Acad Sci USA. 2015; 112: Yee DA, Atayee RS, Best BM, Ma JD. Observations on the urine metabolic profile of codeine in pain patients. J Anal Toxicol. 2014; 38: Yee DA, Hughes MM, Guo AY, Barakat NH, Tse SA, Ma JD, Best BM, Atayee RS. Observation of improved adherence with frequent urine drug testing in pain patients. J Opioid Manag 2014; 10: Zeeman AM, van Amsterdam SM, McNamara CW, Voorberg-van der Wel A, Klooster EJ, van den Berg A, Remarque EJ, Plouffe DM, van Gemert GJ, Luty A, Sauerwein R, Gagaring K, Borboa R, Chen Z, Kuhen K, Glynne RJ, Chatterjee AK, Nagle A, Roland J, Winzeler EA, Leroy D, Campo B, Diagana TT, Yeung BK, Thomas AW, Kocken CH. KAI407, a potent non-8- aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro. Antimicrob Agents Chemother 2014; 58: Zhu W, Zhang Y, Sinko W, Hensler ME, Molohon KJ, Lindert S, Cao R, Li K, Wang K, Wang Y, Liu YL, Sankovsky A, de Oliveira CA, Mitchell DA, Nizet V, McCammon JA, Oldfield E. Antibacterial drug leads targeting isoprenoid biosynthesis. Proc Natl Acad Sci USA 2013; 110: Zielinski DC, Filipp FV, Bordbar A, Jensen K, Smith JW, Herrgard MJ, Mo ML, Palsson BØ. Pharmacogenomic and clinical data link nonpharmacokinetic metabolic dysregulation to drug side effect pathogenesis. Nat Commun 2015; 6:7101. Zou B, Nagle A, Chatterjee AK, Leong SY, Tan LJ, Sim WL, Mishra P, Guntapalli P, Tully DC, Lakshminarayana SB, Lim CS, Tan YC, Abas SN, Bodenreider C, Kuhen KL, Gagaring K, Borboa R, Chang J, Li C, Hollenbeck T, Tuntland T, Zeeman AM, Kocken CH, McNamara C, Kato N, Winzeler EA, Yeung BK, Diagana TT, Smith PW, Roland J. Lead optimization of imidazopyrazines: a new class of antimalarial with activity on Plasmodium liver stages. ACS Med Chem Lett 2014; 5: AWARDS Victor Nizet, MD UCSD Chancellor's Award for Excellence in Postdoctoral Scholar Mentoring Rady Children s Hospital Award for Excellence in Research, 2013 Brookie M. Best, PharmD, MAS Distinguished Teaching Award, Academic Senate, San Diego Division, University of California, 2014 Top 5 Reviewer, Journal of Acquired Immune Deficiency Syndromes, Clinical Science Section, 2015 Edmund Capparelli, PharmD 2015 Rady Children s Hospital Physician Excellence Award for Excellence in Research Kelly Doran, PhD inspiring Women in STEM National Award, INSIGHT Into Diversity, 2015 Outstanding Faculty, College of Science, SDSU, 2015 Outstanding Teacher-Scholar, Department of Biology, SDSU, 2015 Phi Kappa Phi, Elected as Honorary Faculty, SDSU, 2015 Edward L. Morgan Mentorship Award, SDSU BioScience Center, 2015 Outstanding Mentor, SDSU VP Student Service Award, 2013 Pieter Dorrestein, PhD John Jacob Abel Award, American Society for Pharmacology and Experimental Therapeutics, 2015 Rob Knight, PhD Vilcek Prize for Creative Promise in Biomedical Science, 2015 Thomson Reuters Highly Cited Researcher, 2014 Science Watch, Hottest Scientific Researchers and Research, 2013 Bernhard Palsson, PhD FOSBE Systems Biology Foundation Award, 2015 Keynote Lecture, COBRA Conference, 2015 The 20th Aline U. and James M. Orten Memorial Lecture, 2015 Selected by Thomson Reuters as one of The World s Most Influential Scientific Minds, UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 197

100 Infectious Diseases 198 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 199

101 INTRODUCTION FACULTY The Division of Infectious Diseases provides clinical care, teaching, clinical and basic research as well as hospital epidemiology and infection control at Rady Children s Hospital San Diego (RCHSD). The division has excelled in every aspect of its clinical and academic missions. Its reputation is demonstrated by the leadership roles of its divisional members nationally and internationally, and the success of the fellows graduating from the program. DIVISION FAST FACTS Stephen A. Spector, MD Distinguished Professor Co-Division Chief John S. Bradley, MD Professor of Clinical Pediatrics Co-Division Chief Grant Campbell, PhD Assistant Project Scientist Christopher Cannavino, MD Associate Clinical Professor Juan Chaparro, MD Assistant Clinical Professor $10.4 Million in Research Grants The Division covers all the clinical activities in Infectious Diseases at RCHSD Alice Pong, MD Clinical Professor Mark H. Sawyer, MD Professor of Clinical Pediatrics Kumud Singh, PhD Associate Adjunct Professor Rolando Viani, MD Professor of Clinical Pediatrics MAJOR PLANS AND GOALS FELLOWS ES Lauge Farnaes, MD, PhD Ankita Garg, PhD Pratima Rawat, PhD Carmen Teodorof, PhD Gang Zhang, PhD Recruitment of new clinical and laboratory based faculty: Clinical Program: The Pediatric Infectious Diseases Division has established an outstanding clinical infectious diseases consultative service as well as an infectious diseases specialty service at RCHSD. Teaching: The Infectious Diseases faculty has an established record of outstanding teaching and mentoring of medical students, residents and fellows, with one of the ID faculty receiving the UCSD Pediatric Resident Attending of the Year Award. Teaching: The Infectious Diseases faculty has an established record of outstanding teaching and mentoring of medical students, residents and fellows, with one of the ID faculty receiving the UCSD Pediatric Resident Attending of the Year Award. 200 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report CLINICAL ACTIVITIES The division s clinical activity is primarily consultative assisting other medical and surgical divisions in the management of serious, complicated or unusual infections in children in both the inpatient and outpatient settings. The Division of Infectious Diseases provides care and on-service direct teaching of students, pediatric and pharmacy residents, and fellows in the diagnosis and management of pediatric infectious diseases. The ID service begins rounds each day in microbiology, where cultures, stains and histology are reviewed, followed by radiology rounds and ward rounds, and visits to the Emergency Department to provide a superb hands-on teaching experience. John S. Bradley, MD Lecturer, RCHSD Noon Conferences Inpatient rounds and weekly case conferences, Pediatric Infectious Diseases TEACHING ACTIVITIES Christopher R. Cannavino, MD Lecturer, RCHSD Noon Conferences Inpatient rounds and weekly case conferences, Pediatric Infectious Diseases Juan Chaparro, MD Inpatient rounds and weekly case conferences, Pediatric Infectious Diseases Lecturer, RCHSD Noon Conferences Alice Pong, MD Lecturer, RCHSD Noon Conferences Inpatient rounds and weekly case conferences, Pediatric Infectious Diseases Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 201

102 Mark Sawyer, MD Pediatric Residency Director Directs a focused curriculum on immunizations for primary care residents Lecturer, Pediatric Infectious Diseases Inpatient rounds and weekly case conferences, Pediatric Infectious Diseases ISP student advisor Kumud K Singh, PhD Instructor, Problem Based Learning Curriculum for First and Second year Medical Undergraduate Students (Clinical Foundations I SOMC 224ABC Instructor, Pediatrics Pharmacogenetics and Pharmacogenomics (PHAR 235/ BIOM235) John S. Bradley, MD is involved in Phase I through Phase IV clinical trials of antibacterials, antifungals, and non-hiv antivirals, and currently focuses on novel therapies for CA-MRSA and multi-drug resistant GNRs, incorporating pharmacokinetics/ pharmacodynamics and Monte Carlo Simulation into clinical outcome assessment. He served on the FDA s Anti-Infectives Advisory Drug Committee, and continues currently as an Advisor. He is a participant in the Clinical Trials Transformation Initiative (FDA and Pharmaceutical Industry with Duke University) and the Critical Path Initiative to improve clinical trial design for antiinfectives in children. He is a member of USCAST, an affiliate of EUCAST, to help determine antibiotic breakpoints based on in vitro susceptibility and animal model/human infection data with PK/ PD modeling for both generic and branded antibiotics. He sits on the federal advisory committee for the Secretary HHS, the National Preparedness and Response Science Board to advise on issues of bioterrorism and natural/manmade disasters. He s also a member of the CDC s Botulism Bioterror Working Group. He is the editorin-chief of the AAP s Nelson s Pediatric Antimicrobial Therapy with John Nelson, and is a member of the editorial boards of the Journal of the Pediatric Infectious Diseases Society and the Pediatric Infectious Disease Journal. Grant Campbell, PhD studies the mechanisms that control autophagy in response to HIV-1 and M. tuberculosis infection by developing our understanding of how the endo/lysosomal system of macrophages is converted into providing a niche environment for controlled replication by M. tuberculosis and HIV-1. With a view to controlling infection, he is in the process of identifying pharmacological agents that induce autophagic flux and inhibit both HIV-1 and M. tuberculosis in macrophages. Through this work he has shown that the active metabolite of vitamin D induces autophagy and inhibits both HIV-1 and M. tuberculosis infection of macrophages. Juan Chaparro, MD is completing a concurrent fellowship in medical informatics through the Division of Biomedical Informatics (DBMI) at UCSD. His primary research interests include the use of applied informatics and natural language processing to provide point-of-care clinical decision support. In collaboration with the Kawasaki Disease Research Center and the DBMI, he has aided in the creation of an NLP tool to identify the signs of Kawasaki Disease using physician documentation in the emergency department to improve early recognition of the disease. This tool is planning to be implemented into the Rady Epic EHR for further prospective studies. Dr. Chaparro has also collaborated with the development of a registry to identify high-risk patients eligible for Palivizumab prophylaxis and to ensure continued administration through the RSV season. He is also interested in improving physician documentation, and investigating the data integrity of the problem list. As a use-case he has created a best-practice alert to improve documentation of elevated BMIs in the pediatric population to aid in future registry creation and decision support. Dr. Chaparro is also 202 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Organizer, Children Health Education and Research Seminars (CHERS) Stephen A. Spector, MD Instructor, Medical Microbiology for second-year medical students Instructor, Medical Microbiology Laboratory Lecturer, Pediatric Infectious Diseases Lecturer Infectious Disease Fellowship series Lecturer Military International HIV Training Program Inpatient rounds and weekly case conferences, Pediatric Infectious Diseases Member of PhD committees for biomedical sciences students ISP student advisor RESEARCH ACTIVITIES involved in a multidisciplinary investigation into the microbiome/ metabolome of patients with Cystic Fibrosis with a particular focus into how antibiotic treatment courses during acute exacerbations affect the microbiome/metabolome. Alice Pong, MD has a keen interest in pediatric tuberculosis and participates in collaborative studies defining the cellular immune responses of children with acute and latent tuberculosis infections. Current research includes studying the efficacy of an interferon gamma assay to detect tuberculosis infection in children. She is also the hospital epidemiologist and is involved in clinical research studies related to infection control. She also directs the hospital antimicrobial stewardship program and manages initiatives related to stewardship. Mark H. Sawyer, MD focuses his research activities on immunizations through a contract with the San Diego County Health and Human Services Agency Immunization Program. This program is involved in all aspects of immunization including immunization policy, assessment of immunization coverage levels, education of providers and the community about immunizations, promotion of San Diego s computerized regional immunization information system, and focused research into ways to improve immunization delivery. Kumud K. Singh, PhD lab is involved in understanding the unique role of innate immunity in HIV-1 neuropathogenesis and neurodegenerative diseases. His lab focuses on how complement activation in HIV-1 infected brain leads to immune complex deposition, neuroinflammatory cytokine response and HIV-1 associated neurocognitive disorders. The Singh lab hypothesizes that complement activation is a common mechanism of neuroinflammation and CNS impairment due to an infection (HIV), autoimmunity (multiple sclerosis) and aging related consequences (Alzheimer s disease). Stephen A. Spector, MD has sought to discover novel approaches for the detection, treatment, prevention and immunopathogenesis of HIV and human cytomegalovirus (CMV). His laboratory has been involved with HIV/AIDS research since the beginning of the epidemic. Current ongoing research examines HIV pathogenesis with a particular emphasis on host-virus interactions, and the associations of host genetic variants on HIV diseases progression and HIV-related diseases including CNS impairment in children and adults. The laboratory s interest in the identification of host factors that affect HIV pathogenesis led to the novel finding that during permissive infection, HIV down-regulates autophagy to promote its own replication, and the induction of autophagy (using mtor inhibitors as well as vitamin D3) inhibits HIV replication. The laboratory has also identified specific host genetic variants that are associated with mother-to-child transmission, HIV disease progression, and antiretroviral pharmacokinetics and adverse effects. This research has led to his laboratory examining the association of host factors that control HIV replication with the goal of identifying novel strategies to eradicate HIV from those infected. Dr. Spector also directs the Mother-Child-Adolescent HIV Program that provides care, social service, case management and research opportunities for HIV-infected and affected women, pregnant women, youth and children. PUBLICATIONS Nachman S, Alvero C, Acosta EP, Teppler H, Homony B, Graham B, Fenton T, Xu X, Rizk ML, Spector SA, Frenkel LM, Worrell C, Handelsman E, Wiznia A. Pharmacokinetics and 48-Week Safety and Efficacy of Raltegravir for Oral Suspension in Human Immunodeficiency Virus Type-1-Infected Children 4 Weeks to 2 Years of Age. J Pediatric Infect Dis Soc Dec;4(4):e doi: /jpids/piu146. Epub 2015 Feb 7. PubMed PMID: ; PubMed Central PMCID: PMC Brummel SS, Singh KK, Maihofer AX, Farhad M, Qin M, Fenton T, Nievergelt CM, Spector SA. Associations of Genetically Determined Continental Ancestry with CD4+ Count and Plasma HIV-1 RNA beyond Self-Reported Race and Ethnicity. J Acquir Immune Defic Syndr Nov 3. [Epub ahead of print] PubMed PMID: Campbell GR, Rawat P, Bruckman RS, Spector SA. Human Immunodeficiency Virus Type 1 Nef Inhibits Autophagy through Transcription Factor EB Sequestration. PLoS Pathog Jun 26;11(6):e doi: /journal.ppat ecollection 2015 Jun. PubMed PMID: ; PubMed Central PMCID: PMC Marsit CJ, Brummel SS, Kacanek D, Seage GR 3rd, Spector SA, Armstrong DA, Lester BM, Rich K; Pediatric HIV/AIDS Cohort Studies Network. Infant peripheral blood repetitive element hypomethylation associated with antiretroviral therapy in utero. Epigenetics. 2015;10(8): doi: / PubMed PMID: ; PubMed Central PMCID: PMC Curtis DJ, Muresan P, Nachman S, Fenton T, Richardson KM, Dominguez T, Flynn PM, Spector SA, Cunningham CK, Bloom A, Weinberg A. Characterization of functional antibody and memory B-cell responses to ph1n1 monovalent vaccine in HIV-infected children and youth. PLoS One Mar 18;10(3): e doi: /journal.pone ecollection PubMed PMID: ; PubMed Central PMCID: PMC Chaparro JD, Leake JAD. Parasitic disease in the pediatric intensive care unit A review of severe manifestations of pediatric parasitic disease. Journal of Pediatric Intensive Care. 2014; 3: Chaparro J, Murphy E, Davis CJ, Viani RM, Pong A. Case Report: Chest pain and shortness of breath in a previously healthy teenager. Journal of the Pediatric Infectious Diseases Society 2014; doi: /jpids/piu036. Andrade RM, Chaparro JD, Capparelli E, Reed SL (2014) Auranofin Is Highly Efficacious against Toxoplasma gondii In Vitro and in an In Vivo Experimental Model of Acute Toxoplasmosis. PLoS Negl Trop Dis 8(7): e2973. doi: /journal.pntd Moodley A, Spector SA. Single high-dose vitamin D at birth corrects vitamin D deficiency in infants in Mexico. Int J Food Sci Nutr May;66(3): doi: / Epub 2015 Jan 13. PubMed PMID: ; PubMed Central PMCID: PMC Campbell GR, Bruckman RS, Chu YL, Spector SA. Autophagy induction by histone deacetylase inhibitors inhibits HIV type 1. J Biol Chem Feb 20;290(8): doi: /jbc. M Epub 2014 Dec 24. PubMed PMID: ; PubMed Central PMCID: PMC Garg A, Rawat P, Spector SA. Interleukin 23 produced by myeloid dendritic cells contributes to T-cell dysfunction in HIV type 1 infection by inducing SOCS1 expression. J Infect Dis Mar 1;211(5): doi: /infdis/jiu523. Epub 2014 Sep 18. PubMed PMID: ; PubMed Central PMCID: PMC Mandala WL, Ananworanich J, Apornpong T, Kerr SJ, MacLennan JM, Hanson C, Jaimulwong T, Gondwe EN, Rosenblatt HM, Bunupuradah T, Molyneux ME, Spector SA, Pancharoen C, Gelman RS, MacLennan CA, Shearer WT. Control lymphocyte subsets: can one country's values serve for another's? J Allergy Clin Immunol Sep;134(3): e8. doi: /j.jaci PubMed PMID: ; PubMed Central PMCID: PMC Clarke DF, Acosta EP, Rizk ML, Bryson YJ, Spector SA, Mofenson LM, Handelsman E, Teppler H, Welebob C, Persaud D, Cababasay MP, Wang J, Mirochnick M; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1097 Study Team. Raltegravir pharmacokinetics in neonates following maternal dosing. J Acquir Immune Defic Syndr Nov 1;67(3): doi: / QAI PubMed PMID: ; PubMed Central PMCID: PMC Viani RM, Araneta MR, Spector SA. In-Country Migration and Risk Factors for HIV Acquisition among Pregnant Women in Tijuana, Mexico. J Int Assoc Provid AIDS Care Jun 16. pii: [Epub ahead of print] PubMed PMID: Qin M, Brummel S, Singh KK, Fenton T, Spector SA. Associations of host genetic variants on CD4+ lymphocyte count and plasma HIV- 1 RNA in antiretroviral naïve children. Pediatr Infect Dis J Sep;33(9): doi: /inf PubMed PMID: ; PubMed Central PMCID: PMC Berry SA, Gebo KA, Rutstein RM, Althoff KN, Korthuis PT, Gaur AH, Spector SA, Warford R, Yehia BR, Agwu AL; HIV Research Network. Trends in hospitalizations among children and young adults with perinatally acquired HIV. Pediatr Infect Dis J May;33(5): doi: /INF PubMed PMID: ; PubMed Central PMCID: PMC Pass RF, Nachman S, Flynn PM, Muresan P, Fenton T, Cunningham CK, Borkowsky W, McAuley JB, Spector SA, Petzold E, Levy W, Siberry GK, Handelsman E, Utech LJ, Weinberg A; IMPAACT 1089 Team. Immunogenicity of Licensed Influenza A (H1N1) Monovalent Vaccines in HIV-Infected Children and Youth. J Pediatric Infect Dis Soc Dec;2(4): doi: / jpids/pit040. Epub 2013 Jul 17. PubMed PMID: ; PubMed Central PMCID: PMC Essajee SM, Arpadi SM, Dziuban EJ, Gonzalez-Montero R, Heidari S, Jamieson DG, Kellerman SE, Koumans E, Ojoo A, Rivadeneira E, Spector SA, Walkowiak H; Child Survival Working Group of the Interagency Task Team on the Prevention and Treatment of HIV infection in Pregnant Women, Mothers and Children. Pediatric treatment 2.0: ensuring a holistic response to caring for HIVexposed and infected children. AIDS Nov;27 Suppl 2:S doi: / QAD PubMed PMID: ; PubMed Central PMCID: PMC Nachman S, Zheng N, Acosta EP, Teppler H, Homony B, Graham B, Fenton T, Xu X, Wenning L, Spector SA, Frenkel LM, Alvero C, Worrell C, Handelsman E, Wiznia A; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 Study Team. Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years. Clin Infect Dis Feb;58(3): doi: /cid/cit696. Epub 2013 Oct 21. PubMed PMID: ; PubMed Central PMCID: PMC Garg A, Spector SA. HIV type 1 gp120-induced expansion of myeloid derived suppressor cells is dependent on interleukin 6 and suppresses immunity. J Infect Dis Feb 1;209(3): doi: /infdis/jit469. Epub 2013 Sep 1. PubMed PMID: ; PubMed Central PMCID: PMC Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 203

103 Dehority W, Deville JG, Lujan-Zilbermann J, Spector SA, Viani RM. Effect of HIV genotypic drug resistance testing on the management and clinical course of HIV-infected children and adolescents. Int J STD AIDS Jul;24(7): doi: / Epub 2013 Jul 4. PubMed PMID: Campbell GR, Spector SA. Inhibition of human immunodeficiency virus type-1 through autophagy. Curr Opin Microbiol Jun;16(3): doi: /j.mib Epub 2013 Jun 5. Review. PubMed PMID: ; PubMed Central PMCID: PMC Moodley A, Qin M, Singh KK, Spector SA. Vitamin D-related host genetic variants alter HIV disease progression in children. Pediatr Infect Dis J Nov;32(11): doi: / INF.0b013e31829e4d06. PubMed PMID: ; PubMed Central PMCID: PMC Yehia BR, Agwu AL, Schranz A, Korthuis PT, Gaur AH, Rutstein R, Sharp V, Spector SA, Berry SA, Gebo KA. Conformity of pediatric/ adolescent HIV clinics to the patient-centered medical home care model. AIDS Patient Care STDS May;27(5): doi: /apc PubMed PMID: ; PubMed Central PMCID: PMC Spector SA, Qin M, Lujan-Zilbermann J, Singh KK, Warshaw MG, Williams PL, Jean-Philippe P, Fenton T, Siberry GK; IMPAACT P1065 Protocol Team. Genetic variants in toll-like receptor 2 (TLR2), TLR4, TLR9, and FCγ receptor II are associated with antibody response to quadrivalent meningococcal conjugate vaccine in HIV-infected youth. Clin Vaccine Immunol Jun;20(6): doi: /CVI Epub 2013 Apr 17. PubMed PMID: ; PubMed Central PMCID: PMC Campbell GR, Pallack ZT, Spector SA. Vitamin D attenuates nucleoside reverse transcriptase inhibitor induced human skeletal muscle mitochondria DNA depletion. AIDS Jun 1;27(9): doi: /QAD.0b013e dd. PubMed PMID: ; PubMed Central PMCID: PMC Weinberg A, Muresan P, Fenton T, Richardson K, Dominguez T, Bloom A, Petzold E, Anthony P, Cunningham CK, Spector SA, Nachman S, Siberry GK, Handelsman E, Flynn PM; IMPAACT P1088 study team. High proportions of regulatory B and T cells are associated with decreased cellular responses to ph1n1 influenza vaccine in HIV-infected children and youth (IMPAACT P1088). Hum Vaccin Immunother May;9(5): doi: / hv Epub 2013 Jan 31. PubMed PMID: ; PubMed Central PMCID: PMC Shoji-Kawata S, Sumpter R, Leveno M, Campbell GR, Zou Z, Kinch L, Wilkins AD, Sun Q, Pallauf K, MacDuff D, Huerta C, Virgin HW, Helms JB, Eerland R, Tooze SA, Xavier R, Lenschow DJ, Yamamoto A, King D, Lichtarge O, Grishin NV, Spector SA, Kaloyanova DV, Levine B. Identification of a candidate therapeutic autophagy-inducing peptide. Nature Feb 14;494(7436): doi: /nature Epub 2013 Jan 30. PubMed PMID: ; PubMed Central PMCID: PMC Singh KK, Wang Y, Gray KP, Farhad M, Brummel S, Fenton T, Trout R, Spector SA. Genetic variants in the host restriction factor APOBEC3G are associated with HIV-1-related disease progression and central nervous system impairment in children. J Acquir Immune Defic Syndr Feb 1;62(2): doi: /QAI.0b013e31827ab612. PubMed PMID: ; PubMed Central PMCID:PMC Viani RM, Araneta MR, Spector SA. Parallel rapid HIV testing in pregnant women at Tijuana General Hospital, Baja California, Mexico. AIDS Res Hum Retroviruses Mar;29(3): doi: /AID Epub 2012 Nov 19. PubMed PMID: Sarnquist C, Sawyer M, Calvin K et al. Communicating about vaccines and vaccine safety: what are medical residents learning and what do they want to learn? J Public Health Manag Pract. 2013: 19:40-6 McAuliffe K, Peddecord KM, Wang W, Ralston K, Deguire M, Waters-Montijo K, Sawyer MH. Influenza Vaccination and Its Association With Clinic Use of Evidence-Based Practices and Individual Patient Characteristics, San Diego County, J Public Health Manag Pract Mar;19(2): Nagel AC, Tsou MH, Spitzberg BH, An L, Gawron JM, Gupta DK, Yang JA, Han S, Peddecord KM, Lindsay S, Sawyer MH. The complex relationship of real space events and messages in cyberspace: case study of influenza and pertussis using tweets. J Med Internet Res Oct 24;15(10):e237. doi: /jmir.2705 Rosenblum E, McBane S, Wang W, Sawyer M. Protecting newborns by immunizing family members in a hospital-based vaccine clinic: a successful program during the 2010 California pertussis epidemic. Public Health Reports 129: Djibo DA, Peddecord KM, Wang W, Ralston K, Sawyer MH. Factors Associated With Missed Opportunities for Influenza Vaccination: Review of Medical Records in a Diverse Sample of Primary Care Clinics, San Diego County, J Prim Care Community Health Nov 27. pii: Ly E, Peddecord M, Wang W, Ralston K, Sawyer MH. Using academic detailing to improve childhood influenza vaccination rates in San Diego. Public Health Rep. 2015: 130(2): Morris J, Wang W, Wang L, Peddecord KM, Sawyer MH. Comparison of reminder methods in selected adolescents with records in an immunization registry. J Adolesc Health 2015:56 (5 Suppl): s CLINICAL GUIDELINES Schillie S, Murphy TV, Sawyer M, Ly K, Hughes E, Jiles R, de Perio MA, Reilly M, Byrd K, Ward JW; Centers for Disease Control and Prevention (CDC). CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR 2013; 62 (RR-10):1-19. Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney- Delman D, Pavia AT; Committee on Infectious Diseases and Disaster Preparedness Advisory Council. Pediatric anthrax clinical management. Pediatrics May;133(5):e doi: / peds PubMed PMID: American Academy Committee on Infectious Diseases. Updated recommendations on the use of meningococcal vaccines. Pediatrics. 2014Aug;134(2): doi: /peds American Academy Committee on Infectious Diseases; American Academy Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014, Aug;134(2): doi: /peds Committee on Infectious Diseases; American Academy. Recommendations for prevention and control of influenza in children, Pediatrics Nov;134(5):e doi: /peds Epub 2014 Sep 22 Committee on Infectious Diseases: American Academy. Immunization for Streptococcus pneumoniae Infections in High- Risk Children. Pediatrics Dec;134(6): doi: / peds Starke JR; Committee on Infectious Diseases: American Academy Interferon-γ Release Assays for Diagnosis of Tuberculosis Infection and Disease in Children. Pediatrics Dec;134(6):e doi: /peds Orenstein WA; Committee on Infectious Diseases: American Academy Eradicating Polio: How the World's Pediatricians Can Help Stop This Crippling Illness Forever. Pediatrics Jan;135(1): doi: /peds Committee on Infectious Diseases: American Academy. Recommended childhood and adolescent immunization schedule -United States, Pediatrics. 2015; 135(2): Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1- Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at gov/contentfiles/lvguidelines /PerinatalGL.pdf Kimberlin DW, Acosta EP, Prichard MN, Sánchez PJ, Ampofo K, Lang D, Ashouri N, Vanchiere JA, Abzug MJ, Abughali N, Caserta MT, Englund JA, Sood SK, Spigarelli MG, Bradley JS, Lew J, Michaels MG, Wan W, Cloud G, Jester P, Lakeman FD, Whitley RJ; for the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Oseltamivir Pharmacokinetics, Dosing, and Resistance Among Children Aged <2 Years With Influenza. J Infect Dis Mar;207(5): Kaplan SL, Barson WJ, Ling-Lin P, Romero JR, Bradley JS, Tan TQ, Hoffman JA, Givner LB, Mason EO Jr. Early trends for invasive pneumococcal infections in children following the introduction of the 13-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J Mar;32(3) Hulten KG, Kaplan SL, Lamberth LB, Barson WJ, Romero JR, Lin PL, Bradley JS, Givner LB, Tan TQ, Hoffman JA, Mason EO. Changes in Streptococcus pneumoniae Serotype 19A Invasive Infections in Children from J Clin Microbiol Apr;51(4): Le J, Bradley JS, Murray W, Romanowski GL, Tran TT, Nguyen N, Cho S, Natale S, Bui I, Tran TM, Capparelli EV. Improved Vancomycin Dosing in Children Using Area-Under-the-Curve Exposure. Pediatr Infect Dis J Apr;32(4):e Nieves D, Bradley JS, Gargas J, Mason WH, Lehman D, Lehman SM, Murray EL, Harriman K, Cherry JD. Exchange Blood Transfusion in the Management of Severe Pertussis in Young Infants. Pediatr Infect Dis J Jun;32(6): Committee on infectious diseases. Recommendations for prevention and control of influenza in children, Pediatrics Oct;132(4):e Bradley JS. Which antibiotic for resistant Gram-positives, and why? J Infect Jan;68 Suppl 1:S63-75 Le J, Ngu B, Bradley JS, Murray W, Nguyen A, Nguyen L, Romanowski GL, Vo T, Capparelli EV. Vancomycin Monitoring in Children Using Bayesian Estimation. Ther Drug Monit Jan 21. [Epub ahead of print] Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT, Rubinstein E, Holty JE, Messonnier NE, Smith TL, Pesik N, Treadwell TA, Bower WA; Workgroup on Anthrax Clinical Guidelines. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis Feb;20(2). Samady W, Bush R, Pong A, Andrews A, Fisher ES. Predictors of Clostridium difficile infections in hospitalized children. J Hosp Med Feb;9(2):94-8. Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney- Delman D, Pavia AT; AAP Committee on Infectious Diseases and Disaster Preparedness Advisory Council. Pediatric Anthrax Clinical Management: Executive Summary. Pediatrics Apr 28. [Epub ahead of print] Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney- Delman D, Pavia AT; AAP Committee on Infectious Diseases and Disaster Preparedness Advisory Council. Pediatric Anthrax Clinical Management. Pediatrics Apr 28. [Epub ahead of print] Bradley JS, Kauffman RE, Balis DA, Duffy CM, Gerbino PG, Maldonado SD, Noel GJ. Assessment of Musculoskeletal Toxicity 5 Years after Therapy with Levofloxacin. Pediatrics Jul;134(1):e Bradley JS, Benzinger D, Bokesch P, Jacobs R. Single-dose Pharmacokinetics of Daptomycin in Pediatric Patients 3-24 Months of Age. Pediatr Infect Dis J Sep;33(9): Samady W, Pong A, Fisher E. Risk factors for the development of Clostridium difficile infection in hospitalized children. Curr Opin Pediatr Oct;26(5): Le J, Ny P, Capparelli E, Lane J, Ngu B, Muus R, Romanowski G, Vo T, Bradley J. Pharmacodynamic Characteristics of Nephrotoxicity Associated with Vancomycin Use in Children. J Ped Infect Dis first published online November 3, 2014 doi: /jpids/piu110. Adam JK, Varan AK, Pong AL, McDonald EC; Centers for Disease Control and Prevention (CDC). Notes from the field: fatal rat-bite fever in a child - San Diego County, California, MMWR Morb Mortal Wkly Rep Dec 19;63(50): Bradley JS, Puttagunta S, Rubino CM, Blumer JL, Dunne M, Sullivan JE. Pharmacokinetics, Safety and Tolerability of Single Dose Dalbavancin in Children 12 through 17. Pediatr Infect Dis J Dec 30. [Epub ahead of print] Kaplan SL, Center KJ, Barson WJ, Ling-Lin P, Romero JR, Bradley JS, Tan TQ, Hoffman JA, Peters TR, Gurtman A, Scott DA, Trammel J, Gruber WC, Hulten KG, Mason EO. Multicenter Surveillance of Streptococcus pneumoniae Isolates from Middle Ear and Mastoid Cultures in the 13-Valent Pneumococcal Conjugate Vaccine Era. Clin Infect Dis May 1;60(9): doi: /cid/civ067. Epub 2015 Feb 3. Bernstein H, Bradley J, Byington C. Influenza : The Flu Season [online course]. PediaLink. 4/15/2015. Olarte L, Barson WJ, Barson RM, Lin PL, Romero JR, Tan TQ, Givner LB, Bradley JS, Hoffman JA, Hultén KG, Mason EO, Kaplan SL. Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in US Children. Clin Infect Dis May 13. pii: civ368. [Epub ahead of print] Le J, Capparelli EV, Wahid U, Wu YS, Romanowski GL, Tran TM, Nguyen A, Bradley JS. Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study. Clin Ther May 29. pii: S (15) doi: /j. clinthera [Epub ahead of print] Cirillo I, Vaccaro N, Castaneda-Ruiz B, Redman R, Cossey V, Bradley JS, Allegaert K. An Open-Label Study to Evaluate the Single- Dose Pharmacokinetics, Safety, and Tolerability of Doripenem in Infants Less Than 12 Weeks Chronological Age. Antimicrob Agents Chemother Aug;59(8): Arnold JC, Bradley JS. Osteoarticular Infections in Children. Infect Dis Clin North Am Sep;29(3): Committee on Infectious Diseases. Recommendations for Prevention and Control of Influenza in Children, Pediatrics Oct;136(4): Cannavino CR, Castaneda-Ruiz B, Redman R, Go O, Cirillo I, Barauskas V, Senatorova G, Emeryk A, Bradley JS. Safety and Tolerability of Doripenem in Hospitalized Children with Complicated Intra-Abdominal Infection, Complicated Urinary Tract Infections and Pneumonia. Pediatr Infect Dis J Nov;34(11): UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 205

104 George H. Talbot, John H. Powers, Steven C. Hoffmann, for the Biomarkers Consortium of the Foundation for the National Institutes of Health CABP-ABSSSI and HABP-VABP Project Teams. Developing Outcomes Assessments as Endpoints for Registrational Clinical Trials of Antibacterial Drugs: 2015 Update From the Biomarkers Consortium of the Foundation for the National Institutes of Health. Clin Infect Dis Dec 13. pii: civ927 [Epub ahead of print]. AWARDS AND HONORS John S. Bradley, MD American Academy Section on Infectious Diseases Award for Lifetime Contribution to Infectious Diseases Education, 2014 Stephen A. Spector, MD Best Doctors in America, 2007-present Who s Who in Medical Sciences Education Senior Advisor to the Office of the U.S. Global AIDS Coordinator RESEARCH SUPPORT Nachman S, Alvero C, Acosta EP, Teppler H, Homony B, Graham B, Fenton T, Xu X, Rizk ML, Spector SA, Frenkel LM, Worrell C, Handelsman E, Wiznia A. Pharmacokinetics and 48-Week Safety and Efficacy of Raltegravir for Oral Suspension in Human Immunodeficiency Virus Type-1-Infected Children 4 Weeks to 2 Years of Age. J Pediatric Infect Dis Soc Dec;4(4):e doi: /jpids/piu146. Epub 2015 Feb 7. PubMed PMID: ; PubMed Central PMCID: PMC Brummel SS, Singh KK, Maihofer AX, Farhad M, Qin M, Fenton T, Nievergelt CM, Spector SA. Associations of Genetically Determined Continental Ancestry with CD4+ Count and Plasma HIV-1 RNA beyond Self-Reported Race and Ethnicity. J Acquir Immune Defic Syndr Nov 3. [Epub ahead of print] PubMed PMID: Campbell GR, Rawat P, Bruckman RS, Spector SA. Human Immunodeficiency Virus Type 1 Nef Inhibits Autophagy through Transcription Factor EB Sequestration. PLoS Pathog Jun 26;11(6):e doi: /journal.ppat ecollection 2015 Jun. PubMed PMID: ; PubMed Central PMCID: PMC Marsit CJ, Brummel SS, Kacanek D, Seage GR 3rd, Spector SA, Armstrong DA, Lester BM, Rich K; Pediatric HIV/AIDS Cohort Studies Network. Infant peripheral blood repetitive element hypomethylation associated with antiretroviral therapy in utero. Epigenetics. 2015;10(8): doi: / PubMed PMID: ; PubMed Central PMCID: PMC Curtis DJ, Muresan P, Nachman S, Fenton T, Richardson KM, Dominguez T, Flynn PM, Spector SA, Cunningham CK, Bloom A, Weinberg A. Characterization of functional antibody and memory B-cell responses to ph1n1 monovalent vaccine in HIV-infected children and youth. PLoS One Mar 18;10(3): e doi: /journal.pone ecollection PubMed PMID: ; PubMed Central PMCID: PMC Chaparro JD, Leake JAD. Parasitic disease in the pediatric intensive care unit A review of severe manifestations of pediatric parasitic disease. Journal of Pediatric Intensive Care. 2014; 3: Chaparro J, Murphy E, Davis CJ, Viani RM, Pong A. Case Report: Chest pain and shortness of breath in a previously healthy teenager. Journal of the Pediatric Infectious Diseases Society 2014; doi: /jpids/piu036. Andrade RM, Chaparro JD, Capparelli E, Reed SL (2014) Auranofin Is Highly Efficacious against Toxoplasma gondii In Vitro and in an In Vivo Experimental Model of Acute Toxoplasmosis. PLoS Negl Trop Dis 8(7): e2973. doi: /journal.pntd Moodley A, Spector SA. Single high-dose vitamin D at birth corrects vitamin D deficiency in infants in Mexico. Int J Food Sci Nutr May;66(3): doi: / Epub 2015 Jan 13. PubMed PMID: ; PubMed Central PMCID: PMC Campbell GR, Bruckman RS, Chu YL, Spector SA. Autophagy induction by histone deacetylase inhibitors inhibits HIV type 1. J Biol Chem Feb 20;290(8): doi: /jbc. M Epub 2014 Dec 24. PubMed PMID: ; PubMed Central PMCID: PMC Garg A, Rawat P, Spector SA. Interleukin 23 produced by myeloid dendritic cells contributes to T-cell dysfunction in HIV type 1 infection by inducing SOCS1 expression. J Infect Dis Mar 1;211(5): doi: /infdis/jiu523. Epub 2014 Sep 18. PubMed PMID: ; PubMed Central PMCID: PMC Mandala WL, Ananworanich J, Apornpong T, Kerr SJ, MacLennan JM, Hanson C, Jaimulwong T, Gondwe EN, Rosenblatt HM, Bunupuradah T, Molyneux ME, Spector SA, Pancharoen C, Gelman RS, MacLennan CA, Shearer WT. Control lymphocyte subsets: can one country's values serve for another's? J Allergy Clin Immunol Sep;134(3): e8. doi: /j.jaci PubMed PMID: ; PubMed Central PMCID: PMC Clarke DF, Acosta EP, Rizk ML, Bryson YJ, Spector SA, Mofenson LM, Handelsman E, Teppler H, Welebob C, Persaud D, Cababasay MP, Wang J, Mirochnick M; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1097 Study Team. Raltegravir pharmacokinetics in neonates following maternal dosing. J Acquir Immune Defic Syndr Nov 1;67(3): doi: / QAI PubMed PMID: ; PubMed Central PMCID: PMC Viani RM, Araneta MR, Spector SA. In-Country Migration and Risk Factors for HIV Acquisition among Pregnant Women in Tijuana, Mexico. J Int Assoc Provid AIDS Care Jun 16. pii: [Epub ahead of print] PubMed PMID: Qin M, Brummel S, Singh KK, Fenton T, Spector SA. Associations of host genetic variants on CD4+ lymphocyte count and plasma HIV- 1 RNA in antiretroviral naïve children. Pediatr Infect Dis J Sep;33(9): doi: /inf PubMed PMID: ; PubMed Central PMCID: PMC Berry SA, Gebo KA, Rutstein RM, Althoff KN, Korthuis PT, Gaur AH, Spector SA, Warford R, Yehia BR, Agwu AL; HIV Research Network. Trends in hospitalizations among children and young adults with perinatally acquired HIV. Pediatr Infect Dis J May;33(5): doi: /INF PubMed PMID: ; PubMed Central PMCID: PMC Pass RF, Nachman S, Flynn PM, Muresan P, Fenton T, Cunningham CK, Borkowsky W, McAuley JB, Spector SA, Petzold E, Levy W, Siberry GK, Handelsman E, Utech LJ, Weinberg A; IMPAACT 1089 Team. Immunogenicity of Licensed Influenza A (H1N1) Monovalent Vaccines in HIV-Infected Children and Youth. J Pediatric Infect Dis Soc Dec;2(4): doi: / jpids/pit040. Epub 2013 Jul 17. PubMed PMID: ; PubMed Central PMCID: PMC Essajee SM, Arpadi SM, Dziuban EJ, Gonzalez-Montero R, Heidari S, Jamieson DG, Kellerman SE, Koumans E, Ojoo A, Rivadeneira E, Spector SA, Walkowiak H; Child Survival Working Group of the Interagency Task Team on the Prevention and Treatment of HIV infection in Pregnant Women, Mothers and Children. Pediatric treatment 2.0: ensuring a holistic response to caring for HIVexposed and infected children. AIDS Nov;27 Suppl 2:S doi: / QAD PubMed PMID: ; PubMed Central PMCID: PMC Nachman S, Zheng N, Acosta EP, Teppler H, Homony B, Graham B, Fenton T, Xu X, Wenning L, Spector SA, Frenkel LM, Alvero C, Worrell C, Handelsman E, Wiznia A; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 Study Team. Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years. Clin Infect Dis Feb;58(3): doi: /cid/cit696. Epub 2013 Oct 21. PubMed PMID: ; PubMed Central PMCID: PMC Garg A, Spector SA. HIV type 1 gp120-induced expansion of myeloid derived suppressor cells is dependent on interleukin 6 and suppresses immunity. J Infect Dis Feb 1;209(3): doi: /infdis/jit469. Epub 2013 Sep 1. PubMed PMID: ; PubMed Central PMCID: PMC Dehority W, Deville JG, Lujan-Zilbermann J, Spector SA, Viani RM. Effect of HIV genotypic drug resistance testing on the management and clinical course of HIV-infected children and adolescents. Int J STD AIDS Jul;24(7): doi: / Epub 2013 Jul 4. PubMed PMID: Campbell GR, Spector SA. Inhibition of human immunodeficiency virus type-1 through autophagy. Curr Opin Microbiol Jun;16(3): doi: /j.mib Epub 2013 Jun 5. Review. PubMed PMID: ; PubMed Central PMCID: PMC Moodley A, Qin M, Singh KK, Spector SA. Vitamin D-related host genetic variants alter HIV disease progression in children. Pediatr Infect Dis J Nov;32(11): doi: / INF.0b013e31829e4d06. PubMed PMID: ; PubMed Central PMCID: PMC Yehia BR, Agwu AL, Schranz A, Korthuis PT, Gaur AH, Rutstein R, Sharp V, Spector SA, Berry SA, Gebo KA. Conformity of pediatric/ adolescent HIV clinics to the patient-centered medical home care model. AIDS Patient Care STDS May;27(5): doi: /apc PubMed PMID: ; PubMed Central PMCID: PMC Spector SA, Qin M, Lujan-Zilbermann J, Singh KK, Warshaw MG, Williams PL, Jean-Philippe P, Fenton T, Siberry GK; IMPAACT P1065 Protocol Team. Genetic variants in toll-like receptor 2 (TLR2), TLR4, TLR9, and FCγ receptor II are associated with antibody response to quadrivalent meningococcal conjugate vaccine in HIV-infected youth. Clin Vaccine Immunol Jun;20(6): doi: /CVI Epub 2013 Apr 17. PubMed PMID: ; PubMed Central PMCID: PMC Campbell GR, Pallack ZT, Spector SA. Vitamin D attenuates nucleoside reverse transcriptase inhibitor induced human skeletal muscle mitochondria DNA depletion. AIDS Jun 1;27(9): doi: /QAD.0b013e dd. PubMed PMID: ; PubMed Central PMCID: PMC Weinberg A, Muresan P, Fenton T, Richardson K, Dominguez T, Bloom A, Petzold E, Anthony P, Cunningham CK, Spector SA, Nachman S, Siberry GK, Handelsman E, Flynn PM; IMPAACT P1088 study team. High proportions of regulatory B and T cells are associated with decreased cellular responses to ph1n1 influenza vaccine in HIV-infected children and youth (IMPAACT P1088). Hum Vaccin Immunother May;9(5): doi: / hv Epub 2013 Jan 31. PubMed PMID: ; PubMed Central PMCID: PMC Shoji-Kawata S, Sumpter R, Leveno M, Campbell GR, Zou Z, Kinch L, Wilkins AD, Sun Q, Pallauf K, MacDuff D, Huerta C, Virgin HW, Helms JB, Eerland R, Tooze SA, Xavier R, Lenschow DJ, Yamamoto A, King D, Lichtarge O, Grishin NV, Spector SA, Kaloyanova DV, Levine B. Identification of a candidate therapeutic autophagy-inducing peptide. Nature Feb 14;494(7436): doi: /nature Epub 2013 Jan 30. PubMed PMID: ; PubMed Central PMCID: PMC Singh KK, Wang Y, Gray KP, Farhad M, Brummel S, Fenton T, Trout R, Spector SA. Genetic variants in the host restriction factor APOBEC3G are associated with HIV-1-related disease progression and central nervous system impairment in children. J Acquir Immune Defic Syndr Feb 1;62(2): doi: /QAI.0b013e31827ab612. PubMed PMID: ; PubMed Central PMCID:PMC Viani RM, Araneta MR, Spector SA. Parallel rapid HIV testing in pregnant women at Tijuana General Hospital, Baja California, Mexico. AIDS Res Hum Retroviruses Mar;29(3): doi: /AID Epub 2012 Nov 19. PubMed PMID: Sarnquist C, Sawyer M, Calvin K et al. Communicating about vaccines and vaccine safety: what are medical residents learning and what do they want to learn? J Public Health Manag Pract. 2013: 19:40-6 McAuliffe K, Peddecord KM, Wang W, Ralston K, Deguire M, Waters-Montijo K, Sawyer MH. Influenza Vaccination and Its Association With Clinic Use of Evidence-Based Practices and Individual Patient Characteristics, San Diego County, J Public Health Manag Pract Mar;19(2): Nagel AC, Tsou MH, Spitzberg BH, An L, Gawron JM, Gupta DK, Yang JA, Han S, Peddecord KM, Lindsay S, Sawyer MH. The complex relationship of real space events and messages in cyberspace: case study of influenza and pertussis using tweets. J Med Internet Res Oct 24;15(10):e237. doi: /jmir.2705 Rosenblum E, McBane S, Wang W, Sawyer M. Protecting newborns by immunizing family members in a hospital-based vaccine clinic: a successful program during the 2010 California pertussis epidemic. Public Health Reports 129: Djibo DA, Peddecord KM, Wang W, Ralston K, Sawyer MH. Factors Associated With Missed Opportunities for Influenza Vaccination: Review of Medical Records in a Diverse Sample of Primary Care Clinics, San Diego County, J Prim Care Community Health Nov 27. pii: Ly E, Peddecord M, Wang W, Ralston K, Sawyer MH. Using academic detailing to improve childhood influenza vaccination rates in San Diego. Public Health Rep. 2015: 130(2): Morris J, Wang W, Wang L, Peddecord KM, Sawyer MH. Comparison of reminder methods in selected adolescents with records in an immunization registry. J Adolesc Health 2015:56 (5 Suppl): s Clinical Guidelines Schillie S, Murphy TV, Sawyer M, Ly K, Hughes E, Jiles R, de Perio MA, Reilly M, Byrd K, Ward JW; Centers for Disease Control and Prevention (CDC). CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR 2013; 62 (RR-10):1-19. Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney- Delman D, Pavia AT; Committee on Infectious Diseases and Disaster Preparedness Advisory Council. Pediatric anthrax clinical management. Pediatrics May;133(5):e doi: / 206 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 207

105 peds PubMed PMID: American Academy Committee on Infectious Diseases. Updated recommendations on the use of meningococcal vaccines. Pediatrics. 2014Aug;134(2): doi: /peds American Academy Committee on Infectious Diseases; American Academy Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014, Aug;134(2): doi: /peds Committee on Infectious Diseases; American Academy. Recommendations for prevention and control of influenza in children, Pediatrics Nov;134(5):e doi: /peds Epub 2014 Sep 22 Committee on Infectious Diseases: American Academy. Immunization for Streptococcus pneumoniae Infections in High- Risk Children. Pediatrics Dec;134(6): doi: / peds Starke JR; Committee on Infectious Diseases: American Academy Interferon-γ Release Assays for Diagnosis of Tuberculosis Infection and Disease in Children. Pediatrics Dec;134(6):e doi: /peds Orenstein WA; Committee on Infectious Diseases: American Academy Eradicating Polio: How the World's Pediatricians Can Help Stop This Crippling Illness Forever. Pediatrics Jan;135(1): doi: /peds Committee on Infectious Diseases: American Academy. Recommended childhood and adolescent immunization schedule -United States, Pediatrics. 2015; 135(2): Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1- Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at gov/contentfiles/lvguidelines /PerinatalGL.pdf Kimberlin DW, Acosta EP, Prichard MN, Sánchez PJ, Ampofo K, Lang D, Ashouri N, Vanchiere JA, Abzug MJ, Abughali N, Caserta MT, Englund JA, Sood SK, Spigarelli MG, Bradley JS, Lew J, Michaels MG, Wan W, Cloud G, Jester P, Lakeman FD, Whitley RJ; for the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Oseltamivir Pharmacokinetics, Dosing, and Resistance Among Children Aged <2 Years With Influenza. J Infect Dis Mar;207(5): Kaplan SL, Barson WJ, Ling-Lin P, Romero JR, Bradley JS, Tan TQ, Hoffman JA, Givner LB, Mason EO Jr. Early trends for invasive pneumococcal infections in children following the introduction of the 13-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J Mar;32(3) Hulten KG, Kaplan SL, Lamberth LB, Barson WJ, Romero JR, Lin PL, Bradley JS, Givner LB, Tan TQ, Hoffman JA, Mason EO. Changes in Streptococcus pneumoniae Serotype 19A Invasive Infections in Children from J Clin Microbiol Apr;51(4): Le J, Bradley JS, Murray W, Romanowski GL, Tran TT, Nguyen N, Cho S, Natale S, Bui I, Tran TM, Capparelli EV. Improved Vancomycin Dosing in Children Using Area-Under-the-Curve Exposure. Pediatr Infect Dis J Apr;32(4):e Nieves D, Bradley JS, Gargas J, Mason WH, Lehman D, Lehman SM, Murray EL, Harriman K, Cherry JD. Exchange Blood Transfusion in the Management of Severe Pertussis in Young Infants. Pediatr Infect Dis J Jun;32(6): Committee on infectious diseases. Recommendations for prevention and control of influenza in children, Pediatrics Oct;132(4):e Bradley JS. Which antibiotic for resistant Gram-positives, and why? J Infect Jan;68 Suppl 1:S63-75 Le J, Ngu B, Bradley JS, Murray W, Nguyen A, Nguyen L, Romanowski GL, Vo T, Capparelli EV. Vancomycin Monitoring in Children Using Bayesian Estimation. Ther Drug Monit Jan 21. [Epub ahead of print] Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT, Rubinstein E, Holty JE, Messonnier NE, Smith TL, Pesik N, Treadwell TA, Bower WA; Workgroup on Anthrax Clinical Guidelines. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis Feb;20(2). Samady W, Bush R, Pong A, Andrews A, Fisher ES. Predictors of Clostridium difficile infections in hospitalized children. J Hosp Med Feb;9(2):94-8. Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney- Delman D, Pavia AT; AAP Committee on Infectious Diseases and Disaster Preparedness Advisory Council. Pediatric Anthrax Clinical Management: Executive Summary. Pediatrics Apr 28. [Epub ahead of print] Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney- Delman D, Pavia AT; AAP Committee on Infectious Diseases and Disaster Preparedness Advisory Council. Pediatric Anthrax Clinical Management. Pediatrics Apr 28. [Epub ahead of print] Bradley JS, Kauffman RE, Balis DA, Duffy CM, Gerbino PG, Maldonado SD, Noel GJ. Assessment of Musculoskeletal Toxicity 5 Years after Therapy with Levofloxacin. Pediatrics Jul;134(1):e Bradley JS, Benzinger D, Bokesch P, Jacobs R. Single-dose Pharmacokinetics of Daptomycin in Pediatric Patients 3-24 Months of Age. Pediatr Infect Dis J Sep;33(9): Samady W, Pong A, Fisher E. Risk factors for the development of Clostridium difficile infection in hospitalized children. Curr Opin Pediatr Oct;26(5): Le J, Ny P, Capparelli E, Lane J, Ngu B, Muus R, Romanowski G, Vo T, Bradley J. Pharmacodynamic Characteristics of Nephrotoxicity Associated with Vancomycin Use in Children. J Ped Infect Dis first published online November 3, 2014 doi: /jpids/piu110. Adam JK, Varan AK, Pong AL, McDonald EC; Centers for Disease Control and Prevention (CDC). Notes from the field: fatal rat-bite fever in a child - San Diego County, California, MMWR Morb Mortal Wkly Rep Dec 19;63(50): Bradley JS, Puttagunta S, Rubino CM, Blumer JL, Dunne M, Sullivan JE. Pharmacokinetics, Safety and Tolerability of Single Dose Dalbavancin in Children 12 through 17. Pediatr Infect Dis J Dec 30. [Epub ahead of print] Kaplan SL, Center KJ, Barson WJ, Ling-Lin P, Romero JR, Bradley JS, Tan TQ, Hoffman JA, Peters TR, Gurtman A, Scott DA, Trammel J, Gruber WC, Hulten KG, Mason EO. Multicenter Surveillance of Streptococcus pneumoniae Isolates from Middle Ear and Mastoid Cultures in the 13-Valent Pneumococcal Conjugate Vaccine Era. Clin Infect Dis May 1;60(9): doi: /cid/civ067. Epub 2015 Feb 3. Bernstein H, Bradley J, Byington C. Influenza : The Flu Season [online course]. PediaLink. 4/15/2015. Olarte L, Barson WJ, Barson RM, Lin PL, Romero JR, Tan TQ, Givner LB, Bradley JS, Hoffman JA, Hultén KG, Mason EO, Kaplan SL. Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in US Children. Clin Infect Dis May 13. pii: civ368. [Epub ahead of print] Le J, Capparelli EV, Wahid U, Wu YS, Romanowski GL, Tran TM, Nguyen A, Bradley JS. Bayesian Estimation of Vancomycin Pharmacokinetics in Obese Children: Matched Case-Control Study. Clin Ther May 29. pii: S (15) doi: /j. clinthera [Epub ahead of print] Cirillo I, Vaccaro N, Castaneda-Ruiz B, Redman R, Cossey V, Bradley JS, Allegaert K. An Open-Label Study to Evaluate the Single-Dose Pharmacokinetics, Safety, and Tolerability of Doripenem in Infants Less Than 12 Weeks Chronological Age. Antimicrob Agents Chemother Aug;59(8): Arnold JC, Bradley JS. Osteoarticular Infections in Children. Infect Dis Clin North Am Sep;29(3): Committee on Infectious Diseases. Recommendations for Prevention and Control of Influenza in Children, Pediatrics Oct;136(4): Cannavino CR, Castaneda-Ruiz B, Redman R, Go O, Cirillo I, Barauskas V, Senatorova G, Emeryk A, Bradley JS. Safety and Tolerability of Doripenem in Hospitalized Children with Complicated Intra-Abdominal Infection, Complicated Urinary Tract Infections and Pneumonia. Pediatr Infect Dis J Nov;34(11): George H. Talbot, John H. Powers, Steven C. Hoffmann, for the Biomarkers Consortium of the Foundation for the National Institutes of Health CABP-ABSSSI and HABP-VABP Project Teams. Developing Outcomes Assessments as Endpoints for Registrational Clinical Trials of Antibacterial Drugs: 2015 Update From the Biomarkers Consortium of the Foundation for the National Institutes of Health. Clin Infect Dis Dec 13. pii: civ927 [Epub ahead of print]. RESEARCH SUPPORT DAP-PEDS (PI) 07/01/2009 5/31/2015 $551,621 Cubist Pharmaceuticals An Evaluation of the Safety, Efficacy and Pharmacokinetics of Daptomycin in Pediatric Subjects Aged One to Seventeen Years with Complicated Skin and Skin Structure Infections Caused by Gram- Positive Pathogens BAY / (PI) 04/01/2010 6/30/2014 $114,996 Bayer Healthcare Pharmaceuticals Inc. Safety, Tolerability and Pharmacokinetics of Single Dose Intravenous Moxifloxacin in Pediatric Patients BAY /11643A (PI) 6/1/2010 8/31/2013 $76,673 Healthcare A randomized, double-blind, multicenter trial to evaluate the safety and efficacy of sequential (intravenous, oral) moxifloxacin versus comparator in pediatric subjects with complicated intra-abdominal infection NAI (PI) 10/01/2010 3/31/2015 $74,017 GlaxoSmithKline An Open-Label, Multi-Center, Single Arm Study to Evaluate the Safety and Tolerability of Intravenous Zanamivir in the Treatment of Hospitalized Adult, Adolescent and Pediatric Subjects with Confirmed Influenza Infection 6096A US (PI) 11/01/2010 Current $25,000 Pfizer, Inc. Postmarketing observational study of the impact of prevnar 13 (pneumococcal 13-valent conjugate vaccine) on otitis media in children P03579 (PI) 01/01/2011 7/31/2015 $117,902 Merck & Co Phase 1B Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children with Neutropenia U54HD (PI) 4/1/2012 Current $675,708 NIH Colistimethate Single Dose Pharmacokinetics in Infants and Children U54HD (PI) 7/1/2012 Current $132,536 NIH Plasma and Intracellular Cathelicidin Responses to Infection in Infants and Young Children DAP-PEDBAC (PI) 01/01/ Current $52,612 Cubist Pharmaceuticals A Comparative Evaluation of the Safety, Efficacy and Pharmacokinetics of Daptomycin with Standard of Care in Pediatric Subjects 2-17 Years of Age with Bacteremia caused by Staphylococcus aureus D4280C00014 (PI) 06/01/2013 2/28/2015 $66,126 AstraZeneca A Phase I Study to Assess the Pharmacokinetics, Safety and Tolerability of a Single Dose of Ceftazidime-Avibactam (CAZ-AVI) in Children From 3 Months of Age to <18 Years Who Are Receiving Systemic Antibiotic Therapy for Suspected or Confirmed Infection DAP-PEDOST (PI) 09/01/2013 Current $140,350 Cubist Pharmaceuticals A Multicenter, Randomized, Double-Blinded Comparative Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Daptomycin Versus Active Comparator in Pediatric Subjects with Acute Hematogenous Osteomyelitis Due to Gram-Positive Organisms DUR (PI) 09/01/2013 5/31/2015 $91,290 Durata Therapeutics, International B.V. A phase 1, open label, single dose study to investigate the Pharmacokinetics, safety and tolerability of dalbavancin in hospitalized children aged 3 months to 11 years receiving standard intravenous anti-infective treatment for bacterial infections P (PI) 10/01/2011 7/31/2014 $87,461 Cerexa, Inc. A Multicenter, Randomized, Observer-Blinded, Active- Controlled Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Ceftaroline Versus Comparator in Pediatric Subjects with Acute Bacterial Skin and Skin Structure Infections 208 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 209

106 DORIPED3001 (PI) 08/01/2012 1/31/2014 $121,888 Johnson & Johnson A Prospective, Randomized, Double-Blind, Multicenter Study to Establish the Safety and Tolerability of Doripenem Compared with Meropenem in Hospitalized Children with Complicated Intraabdominal Infections DORIPED3002 (PI) 08/01/ /31/2014 $22,402 Johnson & Johnson A Prospective, Randomized, Double-Blind, Multicenter Study to Establish the Safety and Tolerability of Doripenem Compared with Cefepime in Hospitalized Children With Complicated Urinary Tract Infections P (PI) 11/01/2012 7/31/2014 $ Cerexa, Inc. A Multicenter, Randomized, Observer-Blinded, Active-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Ceftaroline Versus Ceftriaxone in Pediatric Subjects with Community-acquired Bacterial Pneumonia Requiring Hospitalization. Cerexa Protocol P (PI) 01/01/2013 7/31/2014 $189,011 Cerexa, Inc. A Multicenter, Randomized, Observer-Blinded, Active-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Ceftaroline Versus Ceftriaxone Plus Vancomycin in Pediatric Subjects with Complicated Community-acquired Bacterial Pneumonia AI (PI) 01/01/2014 Current $5,000 Retrospective Chart Reviews for the Pediatric Fungal Network RO1 HHSN C (PI) 01/01/2013 Current $12,283 La Jolla Institute for Allergy and Immunology/NIH Identification of HLA Class II T Cell Epitopes from Mycobacterium bovis TF-IT-46 (PI) 7/1/2014 Current $12,781 Forest Grant Review of Emergence of Ceftaroline Resistance in All Children with Cystic Fibrosis at Rady Children's Hospital San Diego Colonized with Methicillin-resistant Staphylococcus aureus, as a Function of Ceftaroline Treatment Exposure Private donation to RCHSD Foundation (PI) 1/1/11-5/31/14 $151,000 Pharmacokinetics and Safety of a Single Dose of Ceftaroline fosamil in Children Ages 6 to Less Than 18 Years with Cystic Fibrosis, Being Treated for Suspected or Confirmed Infection TMC-ORI (PI) 10/1/2014 Current $34,945 The Medicines Company An Open label, Dose-finding, Pharmacokinetics, Safety, and Tolerability Study of Oritavancin Single Dose Infusion in Pediatric Subjects Less Than 18 Years of Age with Suspected or Confirmed Bacterial Infections TF-IT-45 (PI) 11/1/2014 Current $15,158 Forest Grant Prospective Evaluation of Ceftaroline Use and Correlation with Emergence of Resistance in Children with Cystic Fibrosis Colonized with MRSA CE (PI) 2/1/2015 Current $35,964 Cempra/Duke University A Phase 1, Open-label, Multi-center Study to Determine the Pharmacokinetics and Safety of Solithromycin as Add-on Therapy in Adolescents and Children with Suspected or Confirmed Bacterial Infection D3720C00009 (PI) 4/1/2015 Current $41,149 AstraZeneca Open Label, Multicentre Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Ceftaroline in Neonates and Young Infants with Late Onset Sepsis TR (PI) 6/1/2015 Current $75,000 Merck A Phase 3 Study of IV to Oral 6-Day Tedizolid Phosphate Compared with 10-Day Comparator in Subjects 12 to <18 Years with cssti D4280C00015 (PI) 7/1/2015 Current $100,000 AstraZeneca A single blind, randomized, multi-center, active controlled, trial to Evaluate safety, tolerability, pharmacokinetics and efficacy of ceftazidime and avibactam when given in combination with metronidazole, compared with meropenem, in children from 3 months to less than 18 years of age with complicated intraabdominal infections (ciai s) D4280C00015 (PI) 7/1/2015 Current $100,000 AstraZeneca A single blind, randomised, multi-centre, active controlled, trial to evaluate safety, tolerability, pharmacokinetics and efficacy of ceftazidime and avibactam compared with cefepime in children from 3 months to less than 18 years of age with complicated urinary tract infections (cuti s) MK (PI) 12/1/2015 Current $202,000 Merck A Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous (IV) and Powder for Oral Suspension Formulations of Posaconazole (POS) in Immunocompromised Pediatric Subjects with Neutropenia (PI) 10/01/2002 6/30/2015 $23,296,680 County of San Diego, Health and Human Services San Diego Immunization Partnership (PI) 07/01/ /30/2015 $1,999,816 County of San Diego, Health and Human Services South Region Public Health Center (PI) 07/26/ /31/2013 $150,000 Society Adolescent Health & Medicine (SAHM) Innovative Registry-based Outreach Component (IROC) (PI) 02/01/ /31/2013 $103,508 County of San Diego, Health and Human Services San Diego Beacon Health Information Exchange (PI) 3/1/13-2/28/16 $1,502,551 County of San Diego, Health and Human Services Mother, Child Adolescent HIV Program H12HA24781 (PI) 8/1/13-7/31/17 $4,810,184 PHS HRSA Ryan White Title IV Program AI (PI) 12/1/13-11/30/20 $13,317,166 NIH NIAID HIV Centers for Underrepresented Populations in Research CTU HD (PI) 8/1/13-7/31/20 $3,825,561 NIH/Harvard Pediatric HIV/AIDS Cohort Study Initiative HD (PI) 8/1/13-7/31/20 $4,660,097 NIH/Harvard Pediatrics HIV/AIDS Cohort Study Initiative (SMARTT Study) AI (PI) 12/1/13-11/30/20 $377,665 NIH/Johns Hopkins International Maternal Pediatric Adolescent AIDS Clinical Trials Group AI (PI) 12/1/13 11/30/18 $1,294,494 NIH/Children s Hospital Los Angeles IMPAACT Network DNA Immuno-Genetics Specialty Laboratory NS (PI) 8/1/11-3/31/16 $3,795,773 NIH/NIAID Host Genetic Factors Associated with CNS Disease of HIV-Infected Children NS (PI) 5/1/13-4/30/18 $1,939,650 NIH/NINDS Modulating Autophagy to Eradicate HIV-1 from CNS Reservoirs 90-CB-0178 (PI) 9/30/12-9/29/16 $1,900,000 DHHS/ACYF Families First: Comprehensive Support Services for HIV Positive Families Affected by Substance Abuse UCSD Mother Child & Adolescent HIV Program HL (PI) 9/12/14 8/31/16 $717,283 NIH/NHLBI Role of CMV in Heart Disease of HIV-Infected Women and Perinatally Infected Youth AI (PI) 9/12/14 8/31/16 $717,283 NIH/NIAID Biological role of cytomegalovirus in endothelial cell inflammation and atherosclerosis (PI) 3/1/13 10/31/15 $280,084 Christie s Place HD (PI) 08/01/15-7/31/20 $103,265 NIH/Tulane Identifying Genetic Association for Targeted AMP Phenotypes NR (PI) 9/28/10-6/30/15 $11,999 NIH/Miami Mitochondrial Determinants of Metabolic Disease in HIV-Infected Children 1R01MH (PI) 04/01/09-12/31/13 $1,834,690 NIH Mannose Binding Lectin in Neuroinflammation and NeuroAID Grant Campbell (PI) $200,000 UCOP IDEA Award Utilizing autophagy to control HIV and tuberculosis (PI) 4/1/17 3/31/22 $3,018,750 NIH Nanopeptide Targeting of HIV-CNS Reservoirs without Reactivation 210 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 211

107 (PI) 1/1/13-12/31/13 $40,000 San Diego Human Dignity Foundation Retention Focused Case Management: Enhancing the Skills of Vulnerable Youth (PI) 9/1/10-8/31/14 $1,291,050 NIH/Tulane Identifying Genetic Association for Targeted AMP Phenotypes HD (PI) 9/28/10-6/30/15 $11,999 NIH/Miami Mitochondrial Determinants of Metabolic Disease in HIV-Infected Children NR (PI) 6/1/12-12/31/13 $59,201 NIH/Johns Hopkins University International Maternal Pediatric Adolescent AIDS Clinical Trials Group Resource Committee AI (Consortium PI) 01/01/14 12/31/20 $511,065 NIH/UCLA IMPAACT Network Immunology Specialty Laboratory (Consortium PI) 12/01/15-11/30/20 $565,873 NIAID/Johns Hopkins IMPAACT Protocols BRS-IMPCT-S (PI) 8/01/15 7/31/20 $101,715 NICHD/Tulane Systems International Maternal Pediatric Adolescent AIDS Clinical Trials Group AI (PI) 6/1/07-12/31/13 $1,240,980 NIH IMPAACT Network Immunology Specialty Laboratory AI (PI) 6/1/12-12/31/13 $61,404 NIH/Johns Hopkins University International Maternal Pediatric Adolescent AIDS Clinical Trials Group Scientific Committee Vice Chair AI (PI) 6/1/12-12/31/13 $49,611 NIH/Johns Hopkins University International Maternal Pediatric Adolescent AIDS Clinical Trials Group Network Executive Committee AI UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 213

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108 Neonatology 214 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 215

109 INTRODUCTION The Division of Neonatology provides state-of-the-art neonatal services at RCHSD, UCSD Hillcrest Medical Center, and at six additional NICUs throughout the greater San Diego area (208 NICU beds total). The Division provides a regionalized approach to care, participating with all the major delivery services in San Diego, Imperial and Riverside Counties. Faculty members also provide inpatient care to term newborns and transitional care for NICU patients at Hillcrest Medical Center. In addition, the division faculty provides medical and neuro-developmental evaluations of high-risk NICU graduates. This Division continues to grow and excel. US News and World Report now ranks the Division in the top 20 Neonatology Divisions in the United States. Recent additions to our growing faculty ranks bring new expertise in molecular research, genomics, innovative clinical care, and quality improvement. FACULTY DIVISION FAST FACTS Lance Prince, MD, PhD Professor Division Chief Lars Bode, PhD Associate Professor in Residence Jeanne Carroll, MD Assistant Professor Casey Cohen, MD Associate Professor Marva Evans, MD Clinical Professor $3.3 Million in Major Research Grants Provides NICU services in 6 different areas of San Diego county Nabil Fatayerji, MD Associate Professor Erika Fernandez, MD Associate Clinical Professor David Golembeski, MD Clinical Professor Gregory P. Heldt, MD Professor in Residence Jose Honold, MD Clinical Professor MAJOR PLANS AND GOALS Integrate quality metrics across all NICUs within the enterprise to improve outcomes and develop innovative best practices. Develop a new clinical research initiative to produce higher impact, more collaborative patient-based investigations. Eustratia Hubbard, MD Associate Professor Farhad Imam, MD, PhD Assistant Professor in Residence Jae Hong Kim, MD, PhD Clinical Professor Amy Kimball, MD Associate Clinical Professor Gail Knight, MD, MMM Clinical Professor Continue to seek new discoveries and knowledge through basic research and multidisciplinary collaborations in order to better understand how to prevent and treat neonatal diseases. Foster the development of fellows and junior faculty by more formal and comprehensive mentoring structures. Brian Lane, MD Associate Clinical Professor Shelly Lawrence, MD Assistant Clinical Professor Michelle Leff, MD Associate Professor Crystal Le, MD Assistant Clinical Professor Krishelle Leong Marc-Aurele, MD Assistant Professor 216 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 217

110 Lily Martorell-Bendezu, MD Associate Clinical Professor Eniko Sajti, MD, PhD Assistant Clinical Professor Charles Sauer, DO Assistant Clinical Professor Lisa Stellwagen, MD Professor Laurel Moyer, MD Associate Professor Janessa Law, MD Spencer Magargal, MD Nathaly Sweeney, MD Megan Doty, MD Rebecca Cavazos, MD Jamie Overbey, DO Kristina Stillwell, MD Ashraf Baeshu, MD Christopher Gibu, MD Kathryn Keegan, MD FACULTY Sanjay Nigam, MD Professor Evan Y. Snyder, MD, PhD Associate Professor Denise Suttner, MD Clinical Professor FELLOWS Jane O Donnell, MD Clinical Professor Richard Song, MD Assistant Clinical Professor Audra Wise, MD Assistant Professor Nikolai Shalygin, MD Casey Ward, MD Gertrude Oppong-Nonterah, PhD Omar Lakhdari, PhD Sabrina Etzold, PhD Joanna Latasiewicz, PhD Andrew Crain, PhD Lina Mastrangelo, PhD Danhua Zhang, PhD Carlos Ramos, MD Assistant Clinical Professor Mark Speziale, MD, PhD Clinical Professor The Division of Neonatology has continued to grow. Faculty members now staff the Rady Children s Hospital NICUs at Scripps Mercy Hospital in San Diego and Scripps Mercy Hospital Chula Vista. Our expanded partnership with hospitals throughout the community brings the highest-level care and expertise to critically ill newborns throughout the San Diego region. The newly constructed Level III NICU that will be housed within the Jacobs Medical Center on the La Jolla campus is schedule to open in Plans for this state of the art 52-bed NICU include private patient rooms and an innovative MRI scanner designed especially for neonates. The Neuro-NICU program has been established at both Rady Children s Hospital and UCSD Hillcrest Medical Center. A joint venture involving both Neonatology and Pediatric Neurology and Co-Directed by Drs. Crystal Le and Jose Honold, this program continues to provide innovative intensive care for neonates at highest risk of neurodevelopmental impairment. Neonatology faculty members partner with physicians from Pediatric Cardiology and Critical Care to staff the new Rady Children s Hospital 30-bed Acute Cardiac Unit. Comprised of the Cardiovascular Intensive Care Unit (CVICU) and Cardiac Step-down Unit (CSU), this specialized unit cares for all pediatric and neonatal cardiac surgery patients including heart transplant patients. The ACU provides a full range of cardiac intensive care services, including advanced patient monitoring and extracorporeal membrane oxygenation (ECMO). Rady Children s Hospital San Diego The 54-bed neonatal intensive care unit (NICU) at Rady Children s Hospital-San Diego provides Level 4 care, the highest designation available by the American Academy. The Rady NICU is a major referral center for the most critically ill newborns, many with severe heart and lung conditions, birth defects, surgical conditions, or born extremely premature. Specialized services include advanced and complex surgery, ECMO, and dialysis. Our NICU has homelike private and semi-private rooms to help parents bond with their newborns. UC San Diego Medical Center at Hillcrest The 49-bed NICU at UCSD Medical Center at Hillcrest is the San Diego area s only regional Level III unit, providing the highest-level care for critically ill newborns. Partnering with the highest risk delivery service in the area, our faculty members direct multidisciplinary care that continuously achieves excellent clinical outcomes in the smallest, most premature infants. Rady Children s NICU at Scripps Hospital, La Jolla and Encinitas The 14-bed NICU at Scripps Memorial Hospital, La Jolla and the 8-bed NICU at Scripps Memorial Hospital, Encinitas are licensed beds by RCHSD. These units have medical directorship provided by the Division of Neonatology. Faculty neonatologists provide onsite daily care, consultation, and 24 hour on call services. Rady Children s NICU at Scripps Mercy Hospital, San Diego and Chula Vista The Division has recently welcomed the 19-bed NICU at Scripps Memorial Hospital, San Diego and the 10-bed NICU at Scripps Memorial Hospital, Chula Vista into the Rady network. These units have medical directorship provided by the Division of Neonatology. Faculty neonatologists provide onsite daily care, consultation, and 24 hour on call services. Rady Children s NICU at Palomar Medical Center The 12-bed NICU at Palomar Medical Center is a licensed RCHSD facility. The Rady UCSD faculty at Palomar Medical Center provides CLINICAL ACTIVITIES neonatal intensive care coverage for both Palomar Medical Center and Pomerado Hospital. Division faculty members also provide the medical directorship to both NICUs. Rady Children s NICU at Rancho Springs Medical Center The new 13-bed NICU at Rancho Springs Medical Center in Murrieta, California is a licensed RCHSD facility and represents our first expansion of services into Riverside County. Neonatology faculty members provide onsite daily care, consultation, and 24 hour on call services along with medical directorship and oversight. Faculty are partnering with other Department members to expand subspecialist coverage to newborns at Rancho Springs. High-Risk Infant Follow-up NICU graduates a closely followed after discharge by multidisciplinary teams of specially trained caregivers. These clinics provide detailed developmental assessments and help identify children requiring additional services. Drs. Erika Fernandez and Brian Lane direct these clinics at UCSD Hillcrest Medical Center and Rady Children s Hospital. Newborn Services/ Family Maternity Care Center Based at UCSD Hillcrest Medical Center, members of the faculty care for well and at-risk newborns in a family-centered care environment. Division faculty members have been instrumental in attaining Baby Friendly Hospital status and have developed the Supporting Premature Infant Nutrition (SPIN) Program and the Premature Infant Nutrition Clinic (PINC). Newborn Nursery provides care and services to the newly-born and their families at four locations within the UCSD Health System. The Nursery has 31 beds and cares for about 1,800 babies per year. Newborn Nursery providers include: Lisa Stellwagen, MD Breastfeeding support program improvement Quality improvement in premature infant nutrition and human milk feeding Clinical investigations into outcomes and in hospital characteristics of late preterm infants Antibiotic stewardship in newborn/nicu care Neonatal abstinence in infancy; improving outcomes, hospital care and parent education Michelle Leff, MD Interactions between maternal diet, breastmilk composition, and development of obesity and diabetes. Clinical investigations into outcomes and in hospital characteristics of late preterm infants Improvement in clinical care of infants at risk of Neonatal Abstinence Syndrome Hyperbilirubinemia and transcutaneous measurements of bilirubin Eustratia Hubbard, MD Clinical investigations into outcomes and in hospital characteristics of late preterm infants 218 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 219

111 The Division continues to provide clinical training and investigational mentoring for 10 fellows in neonatal-perinatal medicine. In addition, medical students and pediatric housestaff receive both clinical training and didactic teaching at the hands of faculty members at both Rady Children s Hospital and the UCSD Hillcrest Medical Center. The Division of Neonatology annually co-sponsors the Fetus The Division of Neonatology contains a productive group of cellular, molecular, and translational investigators. Division members have recently published in high-impact journals including Cell Stem Cell, Development, PLoS One, Pediatrics, Journal of Biological Chemistry, Journal of Immunology, Journal, and Glia. Research has been supported by both the NIH, foundation, and industry sources. Investigators have presented data at many National and International meetings and received multiple awards. Division members studying the basic mechanisms of disease include Drs. Evan Snyder (neuronal stem cells and disease), Lars Bode (human mild oligosaccharides), Greg Heldt (development of synthetic surfactants), Farhad Imam (genetic response to hypoxia and stress), Lance Prince (inflammation, immunity, and lung development), Jeanne Carroll (lung stem cell biology), Sandra Leibel (stem cell approaches for genetic disease), Eniko Sajti (molecular immunology), and Shelley Lawrence (neonatal immunity and infection). Recent translational/clinical investigations include the impact of music on physiological measures of stress in neonates in the NICU (Dr. Jose Honold), a study of antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, Dr. Mark Speziale), a trial of conservative versus interventional approach to patent ductus arteriosus (PDA TOLERATE; Dr. Erika Fernandez), using flow cytometry to better quantify neutrophil differentiation (FlowNICE: Flow Cytometry for Neutrophil Identification, Classification, and Enumeration; Dr. Shelley Lawrence), and using Untargeted, Large-Scale Metabolomics in Neonatology for Disease Biomarker Discovery (Dr. Farhad Imam). Lars Bode, PhD Biosynthesis and physiological function of human milk oligosaccharides Role of breast milk and unbound complex glycans in development of the intestinal innate immune response. Development of oligosaccharide based therapies to prevent infectious disease and necrotizing enterocolitis. Jeanne Carroll, MD Investigating the molecular signals regulating endoderm development and lung stem cell differentiation. Erika Fernandez, MD Role of adrenal insufficiency and glucocorticoid treatment in cardiovascular instability in critically ill newborns. Innovative approaches to improving care of critically ill preterm infants. David Golembeski, MD Board member for the National Children s Study. Co-PI for the Boston University Birth Defects Monitoring Project. Gregory P. Heldt, MD Development of synthetic and novel lung surfactants. Neural-activated synchronized ventilation and its applications in critically ill neonates. Basic molecular and cellular mechanisms of group-b streptococcal infections in neonates. 220 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report TEACHING ACTIVITIES and Newborn: State of the Art Care Conference. The conference provides attendees with the latest innovations and therapies in neonatal care. Division members also mentor multiple postdoctoral fellows, PhD graduate students, and undergraduate students. Faculty members present over 100 invited lectures annually around the nation and the world. RESEARCH ACTIVITIES Jose Honold, MD Clinical innovation and interventions that improve outcome in critically ill neonates at highest risk of neurodevelopmental impairment. Eustratia (Tia) Hubbard, MD Clinical investigations aimed at improving outcomes in late preterm infants and patients at risk of feeding difficulties. Farhad Imam, MD, PhD Using novel approaches and experimental models to study the molecular and genetic responses to environmental stress. Testing the effects of cellular stress on embryogenesis, particularly heart and brain development, in zebrafish. Jae Hong Kim, MD, PhD Understanding development of gastrointestinal motility in preterm infants. Developing novel noninvasive approaches to personalize critical care management in neonates. Amy Kimball, MD Developing and testing innovative pharmacological treatments for respiratory failure, refractory pain, and pulmonary hypertension in critically ill surgical patients. Shelley Lawrence, MD Developing novel flow cytometry approaches for measuring neutrophil composition and maturation in neonates. Investigation of non-contact biometric infant identification for resource limited settings. Functional and phenotypic differences between neonatal and adult neutrophils. Development of pharmacological agents to regulate inflammatory signaling in necrotizing enterocolitis. Crystal Le, MD Effect of premedication on neonatal intubations by trainees. Clinical approaches to improve outcome in critically ill neonates at high risk for neurodevelopmental impairment. Statewide collaboratives for antibiotics stewardship in the NICU and optimizing NICU length of stay of premature infants. Characterization of premature infants feces for identifying factors contributing to skin irritation. Targeted and selective use of laboratory tests to evaluate early onset neonatal sepsis. Michelle Leff, MD Interactions between maternal diet, breast milk composition, and development of obesity and diabetes. Sandra Leibel, MD Using patient-derived induced pluripotent stem cells to investigate the molecular mechanisms of neonatal lung disease. Molecular pathways regulating alveolar type II cell development and surfactant production. Krishelle Leong Marc-Aurele, MD Development of novel approaches for counseling families in the prenatal and postnatal setting as part of a multi-disciplinary palliative care model developed specifically for newborns. Sanjay Nigam, MD Systems biology approaches to identify mechanisms of kidney branching morphogenesis. Developmental regulation and function of organic acid transporters and the elimination and metabolism of drugs and toxins. Lawrence Prince, MD, PhD Mechanisms linking lung inflammation and abnormal development in bronchopulmonary dysplasia. Developmental biology of lung macrophages Development of the neonatal innate immune response. Carlos Ramos, MD Development of the pulmonary vasculature and its role in neonatal lung disease. Bringing innovative and sustainable approaches to neonatal education and clinical care in developing communities. Eniko Sajti, MD, PhD Chromatin remodeling events during mononuclear phagocyte differentiation. Molecular mechanisms of neonatal lung injury and its relation to chronic lung diseases of childhood. Transcriptional regulation of novel enhancers involved in lung macrophage development. Evan Y. Snyder, MD, PhD Stem cell biology Discovery of novel molecular and cellular mechanisms that regulate stem cell pluripotency and neuronal differentiation. The use of induced pluripotent stem cells to investigate basic disease mechanisms and discover novel treatments specific for individual patients. Mark Speziale, MD, PhD Development and management of the Children s Hospital Neonatology Consortium: Data Sharing and Quality Improvement Initiative, sharing data, information and ideas for benchmarking, research and development of safety and quality improvement initiatives related to congenital diaphragmatic hernia, bronchopulmonary dysplasia, perinatal hypoxic ischemic encephalopathy and gastroschisis. Lisa Stellwagen, MD Breastfeeding support program improvement Quality improvement in premature infant nutrition and human milk feeding Clinical investigations into outcomes and in hospital characteristics of late preterm infants Antibiotic stewardship in newborn/nicu care Neonatal abstinence in infancy; improving outcomes, hospital care and parent education Denise Suttner, MD Development of novel approaches for preventing oxidative lung injury and treating pulmonary hypertension in critically ill neonates. RESEARCH SUPPORT Lars Bode, PhD R01 Subaward (Co-PI) 07/ /2017 $425,037 NIH/NIAID Intestinal and Milk Glycan Expression in Restriction of Neonatal Infections INSPIRE Subaward (Co-PI) 10/ /2017 $104,831 NSF What is Normal Milk? Sociocultural, evolutionary, Environmental, and Microbial Aspects of Human Milk R01 (PI) 08/ /2017 $1,192,137 NIH/NIAID Selective Inhibitors of Plasmodium Falciparum G6PD as Novel Antimalarials R21 (PI) 02/ /2017 $426,250 NIH/NICHD Exploring Oligosaccharide Synthesis in Human Mammary Gland Epithelial Cells Research Award (PI) 07/ /2016 $10,000 UCSD Academic Senate Human Milk Oligosaccharides in the Perinatal Space Innovator Award (PI) 10/ /2016 $100,000 Kenneth Rainin Foundation Exploring complex sugars in mother's milk as new, safe and effective IBD interventions Conference Grant (PI) 08/ /2016 $60,000 Bill & Melinda Gates Foundation ISRHML 2016 Conference, Stellenbosch, South Africa R43 (Multi-PI) 12/ /2016 $65,187 NIH/NICHD Disialyl oligosaccharides as Necrotizing Enterocolitis therapeutics Farhad Imam, MD, PhD KL2 Award (1KL2 TR001444) (PI) 3/1/2016 2/28/19 $300,000 UCSD CTRI Genetic and Molecular Characterization of Hypoxia Resistance via Preconditioning for Prevention of Brain Injury in Term and Preterm Newborn Infants Erika Fernandez, MD Missing award# (PI) 03/01/2009-2/28/2014 $167,250 National Institute for Child Health and Human Development Neonatal Research Network. Randomized Controlled trial of hydrocortisone treatment of hypotension in term and late preterm infants. (PI) 2015 present $18,500 PDA TOLERATE: PDA- TO Leave it Alone or Respond and Treat Early Jae Hong Kim, MD, PhD (PI) Active: 2015 present $315,543 A Prospective, Randomized, Controlled, Double-Blind, Parallel- Group, Phase III Study to Compare the Safety and Efficacy of SMOFlipid 20% to Intralipid 20% in Hospitalized Neonates and Infants requiring 28 days of Parenteral Nutrition Amy Kimball, MD (PI) $60,909 A Randomized, Placebo Controlled, Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and pharmacodynamics (PD) of Intravenous (IV)Acetaminophen for the Treatment of Acute Pain in Pediatric Patients Shelley Lawrence, MD (PI) 09/01/2015 to 06/30/2017 $50,000 Rady Children s Hospital Academic Enrichment Fund Program Flow Cytometry for Neutrophil Identification, Classification, and Enumeration [Flow N.I.C.E. Trial] (PI) 09/01/2010 to 08/31/ Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 221

112 $50,000 The Department Physician Development Grant, OUHSC Systems Biology Approach to Neutrophil Function Lawrence Prince, MD, PhD 2R01HL A1 (PI) 04/15/ /31/2018 $1,550,000 National Heart Lung and Blood Institute FGF-10 Expression in a Fetal Mouse Lung Model of Bronchopulmonary Dysplasia. 1R01HL (Co-PI) 04/01/ /31/2020 $1,937,500 National Heart Lung and Blood Institute Transcriptional Control of Lung Macrophage Development (PI) 08/01/ /31/2017 $234,983 The Gerber Foundation Genomics of Lung Inflammation in Preterm Infants 2014 Pilot Project (CIIPLSP) (PI) 04/01/ /31/2015 $50,000 UCSD Clinical & Translational Research Institute Personalized Genomic Medicine in Preterm Infants AWD CR30_Prince (PI) 05/01/ /30/2015 $48,947 Rady Children s Hospital Personalized Genomic Medicine for Neonatal Lung Disease 1R01HL (PI) 07/01/ /31/2015 $2,712,500 National Heart Lung and Blood Institute Role of Fetal Lung Macrophages in Bronchopulmonary Dysplasia. 1R01HL (Co-PI) 09/01/ /31/2015 $1,170,000 National Heart Lung and Blood Institute Imaging Activated Macrophages in the Lungs. Evan Y. Snyder, MD, PhD (PI) 12/05/ /04/2017 $269,009 Michael J Fox Foundation Mechanistic Link Between LRRK2, Alphasynuclein and Lysosomal Function W81XWH (PI) 05/01/ /30/2018 $249,736 Dept. of Defense Army Enabling Widespread, Minimally-invasive Distribution of Multimodal- Therapeutic hnscs Throughout the Neuroaxis of ALS Mice Mark Speziale, MD, PhD Missing award# (PI) Active 2014 present $46,825 Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP Trial) Denise Suttner, MD Missing award# (PI) Active: 2015 present $73,505 Intravenous Remodulin (Treprostinil) as Addon Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn: A Randomized, Placebo- Controlled, Safety and Efficacy Study PUBLICATIONS Clyman R, Wickremasinghe A, Fernandez E. Catecholamineresistant hypotension following patent ductus arteriosus ligation: The role of adrenal hormones. J Pediatr 164 (6): , PMID: Fernandez EF, Watterberg K, Yoder B, et al. Incidence, management and outcomes of cardiovascular insufficiency in critically ill term and late preterm newborn infants. Amer J Perinatol 31(11):947-56, PMID: Leff M, Hubbard E. Genu Recurvatum. Consultant for Pediatricians 2014;13(11):523. T. Manchenkov, M. P. Pasillas, G. G. Haddad, F. B. Imam (2015). Novel Genes Critical for Hypoxic Preconditioning in Zebrafish Are Regulators of Insulin and Glucose Metabolism. G3 (Bethesda) Apr 3;5(6): doi: /g PubMed PMID: I. G. Woods and F. B. Imam (2015). Transcriptome analysis of severe hypoxic stress during development in zebrafish. Genomics data August 28; 07(025): doi: /j.gdata Sauberan J, Rossi S, Kim JH Stability of dilute oral morphine solution for neonatal abstinence syndrome. Journal of Addiction Medicine, 2013 Mar- Apr;7(2): PMID: Richburg D, Kim JH Real-time bowel ultrasound to characterize intestinal motility in the Clyman R, preterm neonate. Journal of Perinatology, 2013 Aug;33(8): PMID: Chan CS, Kim HY, Autran C, Kim JH, Sinkala M, Kankasa C, Mwiya M, Thea DM, Aldrovandi GM, Kuhn L, Bode L Human milk galectin-3 binding protein (Gal3BP) and breastfeedingassociated HIV transmission. Pediatric Infectious Disease Journal Jul 30. PMID: Fenton TR, Kim JH A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatrics, Apr 20;13:59. PMID: Katheria A, Fleming SE, Kim JH A randomized controlled trial of ultrasound-guided peripherally inserted central catheters compared to standard radiograph in neonates. Journal of Perinatology, 2013 Jun 13. PMID: Fenton TR, Nasser R, Eliasziw M, Kim JH, Bilan D, Sauve R Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant. BMC Pediatrics, 2013 Jun 11;13(1):92. PMID: Shivananda S, Lee KS, Marc-Aurele K, Hellmann J, Braid S, Kim JH Defining the threshold at which healthcare professionals consider withdrawing life sustaining ventilation in neonatology. Journal of Palliative Care and Medicine. Special Edition. May. Kim JH, Chan CS, Vaucher YE, Stellwagen LS Challenges in the practice of human milk nutrition in the neonatal intensive care unit. Early Human Development. 89 Suppl 2:S35-8. PMID: Ganapathy V, Hay JW, Kim JH, Lee ML, Rechtman DJ Long term healthcare costs of infants who survived neonatal necrotizing enterocolitis: a retrospective longitudinal study among infants enrolled in Texas Medicaid. BMC Pediatrics. 13:127 PMID: Marx C, Bridge R, Wolf AK, Rich W, Kim JH, Bode L Human milk oligosaccharide composition differs between donor milk and mother's own milk in the NICU. J Hum Lact. 2014;30(1): PMID Song R, Kim JH, Finer NN, Katheria A The use of electrical cardiometry for continuous cardiac output monitoring in preterm neonates: a validation study. Am J Perinatol Mar 28. PMID: Abrams S, Kim JH, Schanler RJ, Lee ML, Rechtman DJ, and the Prolacta Study group Greater mortality and morbidity in extremely preterm infants fed a diet containing cow milk protein products. Breastfeed Med Jul-Aug;9(6): PMID: Lusk LA, Brown EG, Overcash RT, Grogan TR, Keller RL, Kim JH, Poulain FR, Shew SB, Uy C, DeUgarte DA Multi-institutional practice patterns and outcomes in uncomplicated gastroschisis: a report from the University of California Fetal Consortium (UCfC). J Ped Surg Dec;49(12): PMID: Fenton TR, Kim JH Response. Intrauterine growth references are appropriate to monitor postnatal growth of preterm neonates. BMC Pediatr., Jan 17;14:14. Chan CS, Bode L, Kim JH Galectin-3 binding protein in human preterm infant umbilical cord plasma Short Running Title: Gal3BP in preterm infants. J Neonat Perinatol Med. J Neonatal Perinatal Med. PMID: Kim JH, Chan G, Schanler R, Groh-Wargo S, Bloom B, Dimmit R, Williams L, Baggs G, Barrett-Reis B. J Pediatr Gastroenterol Nutr Dec;61(6): PMID: Lawrence SM, Eckert J, Makoni M, Pereira HA. Is the Use of Complete Blood Counts with Manual Differentials for Determining Neutrophil Composition in Newborns Antiquated? ACLS 2015; 45(4): Lawrence SM, Nandyal R, Hallford G, Anderson M, Hart N. Changes in Hematocrit Following a Blood Transfusion Does Not Influence the Risk for Necrotizing Enterocolitis: A Case-Control Study. JNPM 2014; 7(1): Lammers EM, Johnson PN, Ernst KD, Hagemann TM, Lawrence SM, Williams PK, Anderson MP, Miller JL. Association of Fentanyl with Neurodevelopmental Outcomes in Very-Low-Birthweight- Infants. Annals of Pharmacotherapy. 2014: 48(3); CN Le, DM Garey, TA Leone, JK Goodmar, W Rich, NN Finer; Impact of Premedication on Neonatal Intubations by Pediatric and Neonatal Trainees; Journal of Perinatology 2014: 1-3. J O Donnell, C Cohenmeyer, C Le; Neonate with Hypotrichosis- Lymphedema Telangiectasia and Fatal Pulmonary Hypertension; Neonatology Today. Aug Vol 10. Issue 8 Le C, O Donnell J, Boutin M, Song R. A Case of a Newborn with Absent Sternum. Neonatology Today. April Vol 11. Issue 4 Leff M, Hubbard T. Genu Recurvatum. Consultant for Pediatricians. 2014;13:523. Leff M, Robbins S. Congenital Cataracts. Consultant for Pediatricians. 2015;14: Overcash RT, Marc-Aurele KL, Hull AD, Ramos GA. Maternal Iodine Exposure: A Case of Fetal Goiter and Neonatal Hearing Loss. Pediatrics 2016;137(4):e PMID Sauer CW and Marc-Aurele KL. Attempting to Honor Beliefs of Jehovah s Witnesses at the Edge of Viability in an Infant Born at 23 Week s Gestational Age. Am J Case Rep 2016;17: PMID Sauer CW and Marc-Aurele KL. A Neonate with Susceptibility to Long QT Syndrome Type 6 who presented with Ventricular Fibrillation and Sudden Unexpected Infant Death. Am J Case Rep 2016;17: PMID Overcash RT, Marc-Aurele KL, Hull AD, Ramos GA. Maternal Iodine Exposure: A Case of Fetal Goiter and Neonatal Hearing Loss. Pediatrics 2016;137(4):e PMID Sauer CW and Marc-Aurele KL. Attempting to Honor Beliefs of Jehovah s Witnesses at the Edge of Viability in an Infant Born at 23 Week s Gestational Age. Am J Case Rep 2016;17: PMID Sauer CW and Marc-Aurele KL. A Neonate with Susceptibility to Long QT Syndrome Type 6 who presented with Ventricular Fibrillation and Sudden Unexpected Infant Death. Am J Case Rep 2016;17: PMID English N, Ferrell B, Marc-Aurele K. Primary Palliative Care in the Neonatal Intensive Care Setting: What is Possible? What is Necessary? [Platform]. Symposium session with all three authors at American Academy of Hospice and Palliative Medicine Annual Assembly, Chicago March 2016 Goudy S, Angel P, Jacobs B, Hill C, Mainini V, Smith AL, Kousa YA, Caprioli R, Prince LS, Baldwin HS, Schutte BC. Cell-Autonomous and Non-Cell-Autonomous Roles for Irf6 during Development of the Tongue. PLoS ONE 2013 Feb: 8(2): e56270 English N, Ferrell B, Marc-Aurele K. Primary Palliative Care in the Neonatal Intensive Care Setting: What is Possible? What is Necessary? [Platform]. Symposium session with all three authors at American Academy of Hospice and Palliative Medicine Annual Assembly, Chicago March 2016 Goudy S, Angel P, Jacobs B, Hill C, Mainini V, Smith AL, Kousa YA, Caprioli R, Prince LS, Baldwin HS, Schutte BC. Cell-Autonomous and Non-Cell-Autonomous Roles for Irf6 during Development of the Tongue. PLoS ONE 2013 Feb: 8(2): e56270 Carver BJ, Plosa EJ, Stinnett AM, Blackwell TS, Prince LS. Interactions between NF- κb and SP3 connect inflammatory signaling with reduced FGF-10 expression. J Biol Chem May 24;288(21): Greer RM, Miller JD, Okoh VO, Halloran BA, Prince LS. Epithelialmesenchymal coculture model for studying alveolar morphogenesis. Organogenesis May 14;10(3). Stouch AN, Zaynagetdinov R, Barham WJ, Stinnett AM, Slaughter JC, Yull FE, Hoffman HM, Blackwell TS, Prince LS. IκB Kinase Activity Drives Fetal Lung Macrophage Maturation along a Non-M1/M2 Paradigm. J Immunol Aug 1;193(3): PMID: Plosa EJ, Young LR, Gulleman PM, Polosukhin VV, Zaynagetdinov R, Benjamin JT, Im AM, van der Meer R, Gleaves LA, Bulus N, Han W, Prince LS, Blackwell TS, Zent R. Epithelial Beta1 Integrin is Required for Lung Branching Morphogenesis and Alveolarization. Development Dec;141(24): PMID: Han W, Zaynagetdinov R, Yull FE, Polosukhin VV, Gleaves LA, Tanjore H, Young LR, Peterson TE, Manning HC, Prince LS, Blackwell TS. Molecular Imaging of Folate Receptor Beta Positive Macrophages During Acute Lung Inflammation. Am J Respir Cell Mol Biol Jul;53(1):50-9. PMID: Stouch AN, McCoy AM, Greer RM, Lakhdari O, Yull FE, Blackwell TS, Hoffman HM, Prince LS. Il-1β And Inflammasome Activity Link Inflammation To Abnormal Fetal Airway Development. J Immunol Mar 7. [epub ahead of print] PMID: Morrisey EE, Cardoso WV, Lane RH, Rabinovitch M, Abman SH, Ai X, Albertine KH, Bland RD, Chapman HA, Checkley W, Epstein JA, Kintner CR, Kumar M, Minoo P, Mariani TJ, McDonald DM, Mukouyama YS, Prince LS, Reese J, Rossant J, Shi W, Sun X, Werb Z, Whitsett JA, Gail D, Blaisdell CJ, Lin QS. Molecular determinants of lung development. Ann Am Thorac Soc Apr;10(2):S UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 223

113 Neonatology Review: Q&A. 3 rd Edition 2015, Authors: S. Morton, MD, D. Ehret, MD, S. Ghanta, MD, E. Sajti, MD, PhD, B. Walsh, MD, PhD. Editors: D. Brodsky, MD & C. Martin, MD Fetal and Neonatal Physiology, 5th Edition 2016, edited by Drs. Richard Polin, Steven Abman, David Rowitch, and William Benitz. Developmental Biology of Stem Cells: From the Embryo to the Adult. Authors: E. Snyder, S. Yip, E. Sajti Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4 + T cells, Elife Jul 4;5. pii: e doi: /eLife.10134, Allison KA, Sajti E, Collier JG, Gosselin D, Troutman TD, Stone EL, Hedrick SM, Glass CK. PMID: Grover, T, Brozanski, B, Barry, J, Zaniletti, I, Asselin, J, Durand, D, Short, B, Palloto, E, Dykes, F, Reber, K, Padula, M, Evans, J, and Murthy, K (principle site investigator, M. Speziale, Radys Children s Hospital of San Diego) (2014) High Surgical Burden for Infants with Severe Chronic Lung Disease (scld). Journal of Pediatric Surgery 49: Murthy, K, Savani, RC, Lagatta, MC, Zaniletti, I, Wadhawan R, Truoug, W, Zhang, H, Asselin, JM, Durand DJ, Short, BL, Pallotto, EK, Padula, MA, Dykes, FD, Reber, KM, and Evans, JR (principle site investigator, M. Speziale, Radys Children s Hospital of San Diego) (2014) Predicting Death or Tracheostomy Placement In Infants With Severe Bronchopulmonary Dysplasia. Journal of Perinatology 34: Massaro, AN, Murthy, K, Zaniletti, I, Cook, N, DiGeronimo, R, Dizon, M, Hamrick, SEG, McKay, VJ, Natajan, G, Rao, R, Smith, D, Telesco, R, Wadhawan,R, Asselin, JM, Durand, DJ, Evans JR, Dykes, F, Reber, KM, Padula, MA, Pallotto, EK, Short, BL, Mathur, AM (principle site investigator, M. Speziale, Radys Children s Hospital of San Diego) (2014) Short-term Outcomes After Perinatal Hypoxic Ischemic Encephalopathy: A Report from Children s Hospitals Neonatal Consortium HIE Focus Group. Journal of Perinatology Murthy, K, Yanowitz, TD, DiGeronimo, R, Dykes, FD, Zaniletti, I, Sharma, J, Sullivan, KM, Mirpuri,J, Evans, JR, Wadhawan, R, Piazza, A, Chapman-Adams, I, Asselin, JM, Short, BL, Padula, MA, Duranda, DJ, Pallotto, EK, and Reber, Km (principle site investigator (principle site investigator, M. Speziale, Radys Children s Hospital of San Diego) (2014) Short-Term Outcomes for Preterm Infants with Surgical Necrotizing Enterocolitis. Journal of Perinatology 34: Murthy, K, Evans, J, Bhatia, A, Rothstein, D, Wadhawan, R, Zaniletti, I, Rao, R, Thurm, C, Mathur, A, Piazza, A, Stein, J, Reber, K, Short, B, PAdula, M, Durand, D, Asselin, J, Palloto, E, and Dykes, FD (principle site investigator, M. Speziale, Radys Children s Hospital of San Diego) (2014) The Association of Type of Surgical Closure on Length of Stay Among Infants with Gastrochisis Born > 34 Weeks Gestation. Journal of Pediatric Surgery 49: Murthy, K, Dykes, FD, Padula, MA, Pallotto, EK, Reber, KM, Durand, DJ, Short, BL, Asselin, JM, Zaniletti,I, and Evans, JR (principle site investigator, M. Speziale, Radys Children s Hospital of San Diego) (2014) The Children s Hospitals Neonatal Database: An Overview of Patient Complexity, Outcomes, and Variation in Care. Journal of Perinatology 34: Grover, T, Murthy, K, Brozanski, B, Gien, J, Rintoul, N, Keene, S, Najaf, T, Chicoine, L, Porta, N, Zaniletti, I, Pallotto, E, and the Children s Hospital Neonatal Consortium (principle site investigator, M. Speziale, Radys Children s Hospital of San Diego) (2015) Short- Term Outcomes and Medical and Surgical Interventions in Infants with Congenital Diaphragmatic Hernia. American Journal of Perinatology 32(11): Murphy, D, Henry, C, Kurlen, S, Payton, E, and Powers, R (principle site investigator, M. Speziale, Rady Children's Hospital and Health Center, San Diego, CA) (2015) Platelet Count and Associated Morbidities in VLBW Infants with Pharmacologically Treated Patent Ductus Arteriosus. The Journal Maternal-Fetal & Neonatal Medicine 42: Murthy, K, Pallotto, EK, Gien, J, Brozanski, BS, Porta, NFM, Zaniletti, I, Keene, S, Chicoine, LG, Rintoul, NE, Dykes, FD, Asseline, JM, Short, BL, Padula, MA, Durand, DJ, Reber, KM, Evans, JR, and Grover, TR (principle site investigator, M. Speziale, Radys Children s Hospital of San Diego) (2016) Predicting Death or Extended Length of Stay in Infants with Congenital Diaphragmatic Hernia. Journal of Perinatology: 1-6 Smith GA, Snyder EY, Two cells are better than one: Optimizing stem cell survival by co-grafting "helper" cells that offer regulated trophic support, Experimental Neurology 247: (2013). doi: /j.expneurol PMID: [peer-reviewed]. Smith GA, Snyder EY, Two cells are better than one: Optimizing stem cell survival by co-grafting "helper" cells that offer regulated trophic support, Experimental Neurology 247: (2013). doi: /j.expneurol PMID: [peer-reviewed]. Tobe BTD, Brandel MG, Nye JS, Snyder EY, Implications & limitations of reprogramming for psychiatric drug development, Experimental & Molecular Medicine 45:e59 (2013) doi: / emm PMID: [peer-reviewed]. Oh IH, Snyder, E.Y., Special feature on stem cells: current research and future prospects, Experimental & Molecular Medicine 45:e63. (2013). doi: /emm PMID: Hou J, Tobe BTD, Lo F, Blethrow JD, Crain AM, Wolf DA, Snyder EY, Singec I, Brill LM, Combined total proteomic and phosphoproteomic analysis of human pluripotent stem cells, in Nicholas Zavazava (ed.), Embryonic Stem Cell Immunobiology: Methods and Protocols, Methods in Molecular Biology, vol. 1029, pp , Springer Science+Business Media New York (2013). DOI / _12 Gonzalez, R., Garitaonandia, I., Abramihina, T., Wambua, G.K., Ostrowska, A., Brock, M. Noskov, A., Boscolo, F.S., Craw, J.S., Laurent, L.C., Snyder, E.Y., Semechkin, R.A., Deriving dopaminergic neurons for clinical use. A practical approach, Scientific Reports 3: 1463 (pp 1-5) (DOI: /srep01463) (2013). Ijichi K, Brown, G.D., Moore, C.S., Lee, J-P, Winokur, P.N., Roberto Pagarigan, R., Snyder, E.Y., Bongarzone, E.R., Crocker, S.J. MMP-3 mediates psychosine-induced globoid cell formation: implications for leukodystrophy pathology,, Glia 61(5); (2013). DOI: /glia.2247 Xie H, Poyraz S, Thu M, Liu Y, Snyder EY, Smith JW, Zhang X, Microwave-assisted fabrication of carbon nanotubes decorated polymeric nano-medical platforms for simultaneous drug delivery and magnetic resonance imaging, Royal Society of Chemistry Advances RSC Advances 4(11):5649 (2013). Bignone, P.A., Krupa, R.A., Sternberg, H., Funk, W.D. Snyder, E.Y., West, M.D., Larocca, D., Identification of human embryonic progenitor cell targeting peptides using phage display, PLoS One 8(3):e58200 (2013). Ashwal S, Ghosh N, Turenius CI, Dulcich M, Denham CM, Tone B, Hartman R, Snyder EY, Obenaus A, Reparative effects of neural stem cells in neonatal rats with hypoxic-ischemic injury are not influenced by host gender, Pediatr Res 75(5): (2014). Jan 24. doi: / pr Franklin RJM, Snyder EY, Stem Cells: The end of the beginning, Exp Neurol 260: 1-2 (2014). PMID: Franklin RJM, Snyder EY (eds.), Special Issue: Stem Cells: Newly emerging concepts in the nervous system, Exp Neurol Vol. 260, October, 2014, Elsevier Press, Amsterdam. Li, J., Yu, L., Gu, X., Ma, Y., Pasqualini, R., Arap, W., Snyder, E.Y., Sidman, R.L., Tissue Plasminogen Activator regulates Purkinje neuron development and survival, PNAS (in press). DOI: /pnas Niles WD, Wakeman DR, Snyder EY, Growth dynamics of fetal human neural stem cells in Stem Cells Handbook, 2 nd edition (ed. Sell S), Springer NY (in press). Olee, T, Grogan SP, Lotz M, Colwell Jr CW, D Lima D, Snyder EY, Repair of cartilage defects in arthritic tissue with differentiated human embryonic stem cells, Tissue Engineering 20(3-4): (2014). doi: /ten PMID: Goncharova V, Das S, Niles W, Schraufstatter I, Wong AK, Povaly T, Wakeman D, Miller L, Snyder, E.Y. *, Khaldoyanidi, S. * Homing of neural stem cells from the venous compartment into a brain infarct does not involve conventional interactions with vascular endothelium. Stem Cell Translational Medicine, 3(2): (2014). doi: /sctm [*co-corresponding & senior author] Wakeman DR, Redmond DE Jr, Dodiya HB., Sladek JR Jr., Leranth C, Teng YD, Samulski RJ, Snyder EY, Human neural stem cells survive long-term in the midbrain of dopamine-depleted monkeys after GDNF over-expression, and project neurites toward an appropriate target Stem Cell Transl Med 3: (2014). Song RS, Carroll JM, Acevedo L, Wu D, Liu Y, Snyder EY, Generation, expansion, & differentiation of human induced pluripotent stem cells (hipscs) derived from the umbilical cords of newborns, Current Protocols in Stem Cell Biol 2014 May 16;29:1C C doi: / sc01c16s29. Davies BM, Rikabi S, French A, Pinedo-Villanueva R, Morrey M, Wartolowska K, Sooriakumaran P, Judge A, MacLaren RE, Mathur A, Williams DJ, Wall I, Birchall M, Reeve B, Atala A, Barker RW, Cui Z, Furniss D, Bure K, Snyder EY, Karp JM, Price A, Carr A, Brindley DA, A Quantitative Assessment of Barriers to the clinical development and adoption of cellular therapies: a pilot study, J. Tissue Engineering 5: DOI: / (2014). Lei H, Wong S, Snyder EY, Hamblin MH, Lee J-P, Human neural stem cells rapidly ameliorate symptomatic inflammation in early-stage ischemicreperfusion cerebral injury, Stem Cell Research & Therapy 5:129 (2014) doi: /scrt519 Liu Y, Wu D, Lao D, Peterson C, Elliott KAH, Snyder EY, Laser-assisted generation of human induced pluripotent stem cells, Current Protocols in Stem Cell Biology 31: 4A.1 4A.15 (2014). Claycomb KI, Winokur PN, Johnson KM, Giampetruzzi AW, Sacino AV, Snyder EY, Barbarese E, Bongarzone ER, Crocker SJ, Aberrant production of tenascin-c in globoid cell leukodystrophy alters psychosine-induced microglial functions, J Neuropath Exp Neurol (2014). French A, Bravery C, Wall I, Chandra A, Archibald P, Gold JD, Artzi N, Kim HW, Carr AJ, Barker RW, Reeve B, Meissner A, Wu JC, Knowles JC, Williams D, García-Cardeña G, Sipp D, Rao MS, Oh S, Loring J, Bure K, Stacey G, Karp JM, Snyder EY*, Brindley DA*, Enabling consistency in pluripotent stem cell-derived products for R&D and clinical applications through material standards, Stem Cell Transl Med 4: (2015). doi: /sctm [*co-corresponding & senior author] Gonzalez, R., Garitaonandia, I., Crain AM, Poustovoitov, M., Abramihina, T., Noskov, A., Jiang, C., Morey, R., Laurent, L.C., Elsworth J.D., Snyder, E.Y., Redmond, D.E., Jr., Semechkin, R.A., Proof of concept studies exploring the safety and functional activity of human parthenogeneticderived neural stem cells for the treatment of Parkinson s Disease, Cell Transplantation 24: (2015). Das S, Tobe B, Jain PA, Niles W, Winquist A, Mastrangelo L, Snyder E.Y., The application and future of neural stem cells in regenerative medicine in Atala A, Allickson J (eds) Translational Regenerative Medicine, pp , Elsevier, Amsterdam (2015). Silva M, Daheron L, Hurley H, Bure K, Barker R, Carr AJ, Williams D, Kim H-W, French A, Coffey PJ, Cooper-White JJ, Reeve B, Rao M, Snyder EY, Ng KS, Mead BE, Smith JA, Karp JM, Brindley DA, Wall I, Generating ipscs: Translating cell reprogramming science into scalable and robust biomanufacturing strategies Cell Stem Cell (2015). Acevedo L.M, Lindquist JN, Walsh BM, Sia P, Cimadamore, F., Chen, C., Denzel, M., Ranscht, B, Terskikh, A., Snyder EY*, Cheresh DA*, hesc differentiation toward an autonomic neuronal cell fate depends on distinct cues from the co-patterning vascular cells Stem Cell Reports (2015) [*cocorresponding & senior author]. Song RS, Carroll JM, Acevedo L, Wu D, Liu Y, Snyder EY. Generation, Expansion and Differentiation of Human Induced Pluripotent Stem Cells (hipscs) Derived From the Umbilical Cords of Newborns. Curr Protoc Stem Cell Biol May 16;29:1C C Le C, O Donnell J, Boutin M, Song R. A Case of a Newborn with Absent Sternum. Neonatology Today. April Meyer J, Pascoe B, Schreck PK, Stellwagen L. Hospital-based breastfeeding data collection in the USA. J Hum Lact Feb;29(1):11-4. PMID: Kim JH, Chan CS, Vaucher YE, Stellwagen LM. Challenges in the practice of human milk nutrition in the neonatal intensive care unit. Early Hum Dev Aug 30. PMID: Stellwagen LM, Schanler RJ. Breastfeeding the Newborn. In: Campbell DE, ed. Neonatology for Primary Care. Elk Grove Village, IL: American Academy ; 2014 AWARDS Farhad Imam, MD, PhD UCSD Institutional Nominee and National Finalist, Individual Biomedical Research Award, Hartwell Foundation, TN (2015) Jae Kim, MD, PhD America s Top Physicians (2014) Castle Connolly Top Doctor (2013, 2014) Shelley Lawrence, MD American Academy of Immunology Early Career Travel Grant (2013) Michelle Leff, M.D. UCSD National Center of Leadership in Academic UCSD Academic Senate Travel Grant (04/2014) Medicine Selected Participant (02/ /2013) AAP Special Achievement Award (09/2013) Eniko Sajti, M.D. Best Scientific Presentation: The Neonatal Cardiopulmonary Biology Young Investigators Forum (2014) George von L. Meyer Fund (2014) Evan Snyder, MD, PhD Non-Cardiac Topic-of-the-Year Speaker, 10th International Symposium on Stem Cell Therapy & Cardiovascular Innovation, Madrid, Spain: Stem cells & spinal cord repair (2013) Co-Chair, 2013 World Stem Cell Summit (2013) 2015 Pioneer Award from the NIH Advanced Course in Frontiers in Stem Cells in Cancer Alumnus-of-the-Year & Inductee into Wall-of-Fame, Northeast High School, Philadelphia, PA (2015) Rock Star of Innovation, CONNECT, San Diego (2015) Lisa Stellwagen, MD San Diego s Top Docs UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 225

114 Nephrology 226 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 227

115 INTRODUCTION FACULTY The Division of Pediatric Nephrology is incrediably active in patient care, research and education. Clinically, the division is the only service in San Diego and Imperial County that provides comprehensive care to children with kidney diseases, including acute and chronic dialysis and renal transplantation. The new clinical facilities and arrival of outstanding clinical faculty have energized and revitalized the clinical practice. The Division was recognized in U.S. News and World Report as one of the top Pediatric Nephrology programs in the US: 24th in 2013, 27th in 2014 and 38th in Due to the significant increase in clinical volume, we have been actively recruiting new faculty. Dr. Lieuko Nguyen, who finished fellowship training at Stanford and Toronto Sick Children, started a full time position in October Dr. Sujana Gunta, who trained with us, started a part-time position with us in January Dr. Noureddin Nourbakhsh and Dr. Elliot Perens completed their Fellowship in our program in June They started as Assistant Professors in our division in July The division has a three-year accredited subspecialty fellowship designed to prepare fellows for a career in academic pediatric nephrology. The fellowship program was reviewed by the ACGME in 2008 and was accredited for an additional five years. We have been successful in consistently recruiting outstanding fellowship candidates. Medical students and pediatric residents take electives in pediatric nephrology, spending two to four weeks on both the inpatient and outpatient services with kidney conditions. (Dr. Wei Ding, a Visiting Scholar in Dr. Mak s laboratory, received the Western Society of Pediatric Nephrology (WSPN) Fellow Research Award in September, 2014.) Robert Mak, MD, PhD Professor Division Chief Nadine Benador, MD Clinical Professor Caitlin Carter, MD Assistant Clinical Professor Sujana Gunta, MD Assistant Clinical Professor $100K in Major Research Grants 228 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report DIVISION FAST FACTS MAJOR PLANS AND GOALS National recognition for care of children with kidney disease Expand research program to achieve national recognition for basic and translational science for all current faculty Expand current dialysis, apheresis and kidney transplant services Extramural funding for fellowship program The division performs 8-10 transplants annually and follows more than 80 transplantation patients Elizabeth Ingulli, MD Associate Clinical Professor Lieuko Nguyen, MD Assistant Clinical Professor Most children from San Diego and Imperial Counties with kidney diseases are hospitalized at Rady Children s Hospital San Diego (RCHSD). In addition, the division provides consultations for inpatients with kidney diseases, hypertension and fluid and electrolyte abnormalities. The average inpatient census is There are nine half-days of outpatient clinics weekly, each staffed by one to two faculty members. One clinic is primarily for the follow-up of patients after renal transplantation. In the other seven clinics, the division sees new and established patients with kidney diseases. In addition, there is a fellows continuity clinic, which is staffed with an attending. The Division has started a weekly CCS kidney team clinic with a renal dietician and social worker every Thursday for the management of children with congenital abnomalies and chronic kidney disease. A monthly joint lupus clinic in conjunction with the Division of Rheumatology has also been started and is already fully booked. We have plans to initiate a second monthly lupus clinic. The division has a contract with Kaiser Permanente to see new and established patients with kidney diseases in three weekly half-day clinics. The division FELLOWS Noureddin Nourbakhsh, DO Elliot Perens, MD, PhD Celina Cepeda, MD Peter Yorgin, MD Clinical Professor CLINICAL ACTIVITIES performs 8-10 transplants annually and follows more than 80 transplantation patients. The division also sees inpatient consults at Kaiser Permanente and in the Newborn Intensive Care Units at UCSD Medical Center and Sharp Mary Birch Hospital. Children are treated with either chronic hemodialysis or peritoneal dialysis at UCSD Medical Center and RCHSD. There are daily hemodialysis unit rounds. There are two monthly peritoneal dialysis clinics. The average census of patients on chronic dialysis is 25. We have also taken over the acute dialysis services previously provided by UCSD Medical Center. We are also taking over the apheresis services previously provided by an outside company. The dialysis/ apheresis unit is being renovated and expanded. This is now adjacent to the outpatient nephrology clinics so that we are moving towards our long-term goal of a Comprehensive Kidney Care Center. We have established multi-disciplinary clinics in the context of kidney stones, tuberous sclerosis & lupus nephritis Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 229

116 Fellows: Dr. Caitlin Carter completed her Fellowship in our program in December She started a part time position with us in January Dr. Sujana Gunta completed her Fellowship in our program in September 2013 and started a part-time position with us in January Dr. Dean Nourbakhsh and Dr. Elliot Perens completed their Fellowship in our program in June They started faculty positions with us in July We have applied to the NIH for T32 fellowship training grant funding in association with the Internal Medicine Nephrology Division at UCSD. Residents/Medical Students: An average of 12 pediatric residents per year elect to spend a month in nephrology, and between three and four medical students a year take the nephrology elective. Nadine Benador, MD Actively involved in training medical students, pediatrics residents and fellows in Nephrology Part of the clinical teaching service for inpatient and outpatient pediatrics training for medical students Participates in clinical and didactic teaching for medical students and pediatric resident trainees who elect to spend a month in nephrology Teaches nursing staff in the dialysis area Caitlin Carter, MD Actively involved in training medical students, pediatrics residents and fellows in Nephrology Elizabeth Ingulli, MD Coordinates Grand Rounds for RCHSD since 2011 Director of the Pediatric Nephrology Fellowship Program since 2012 Director, Peds Course 434, Medical Student Pediatric Nephrology Rotation Program from 2012; Curriculum revised Actively involved in training medical students, pediatric residents and fellows in renal transplantation; is the Medical Director of the Pediatric Renal Transplant Program Participates in clinical teaching for medical students, pediatric resident trainees, nephrology fellows, and pharmacy students; participates in didactic lectures for medical students, pediatric resident trainees, and nephrology fellows in general nephrology. Participates in didactic lectures to PICU, IMU and clinic nursing staff in the Management of Pediatric Transplant Patient and Transplant Immunology, The Basics She won the Resident Teaching Award for the second time in Robert Mak, MD, PhD Actively involved in training medical students, pediatric residents and fellows in Nephrology; An average of 12 pediatric residents per Nadine Benador, MD She is active in clinical research. She participated in the national Chronic Kidney Disease in Children Study, and was the local investigator for two multicenter trials. Caitlin Carter, MD She is active in clinical research. She is conducting outcome studies in transitioning pediatric patients to adult care. Elizabeth Ingulli, MD She is active in clinical research. She is conducting outcomes studies in pediatric renal transplantation. She is a recognized expert on immune aspects of renal transplant rejection and is frequently invited speaker in national meetings. 230 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report TEACHING ACTIVITIES year elect to spend a month in nephrology, and between three and four medical students a year take the nephrology elective. Participates in clinical and didactic teaching for medical students and pediatric resident trainees who elect to spend a month in nephrology. Member of the Education Committee of the American Society of Pediatric Nephrology Editorial Board, American Academy, PREP Nephrology, 2013-present Mentors fellows and visiting scholars in basic research in his laboratory. Dr. Wei Ding, a Visiting Scholar in Dr. Mak s laboratory, received the WSPN Fellow Research Award in September, Lieuko Nguyen, MD Actively involved in training medical students, pediatric residents and fellows in nephrology Part of the clinical teaching service for inpatient and outpatient pediatric training for medical students Participates in clinical and didactic teaching for medical students and pediatric resident trainees who elect to spend a month in nephrology. Noureddin Nourbakhsh, DO Actively involved in training medical students, pediatrics residents and fellows in nephrology Part of the clinical teaching service for inpatient and outpatient pediatrics training for medical students Participates in clinical and didactic teaching for medical students and pediatric resident trainees who elect to spend a month in nephrology. Elliot Perens, MD, PhD Actively involved in training medical students, pediatrics residents and fellows in nephrology Part of the clinical teaching service for inpatient and outpatient pediatric training for medical students Participates in clinical and didactic teaching for medical students and pediatric resident trainees who elect to spend a month in nephrology. Peter Yorgin, MD Actively involved in training medical students, pediatric residents and fellows in nephrology Part of the clinical teaching service for inpatient and outpatient pediatrics training for medical students Participates in clinical and didactic teaching for medical students and pediatric resident trainees who elect to spend a month in nephrology. RESEARCH ACTIVITIES Robert Mak, MD, PhD He is active in basic and translational research: (1) Pathophysiology of uremic cachexia. Dr. Mak recently published a number of papers on the significance of cytokine signaling in the pathogenesis of uremic cachexia. Pharmacologic blockade of the pegylated leptin receptor is an exciting novel therapeutic strategy for uremic cachexia. This is recently published in Journal of the American Society of Nephrology, the top nephrology journal, (impact factor 9.3). (2) Genetic regulation of weight and height in children with chronic kidney disease. Dr. Mak is the PI on a genome wide association study with above title within the Chronic Kidney Disease in Children(CKiD) cohort Dr. Mak is a co-principal Investigator for a NIH funded national CKiD study, which follows over 800 patients. He chairs the progression committee. This study has gone extremely well and the investigator team has been renewed for another five years, from 2013 to Lieuko Nguyen, MD She is active in clinical research. She is working on a cell phone based program to monitor compliance in patients with chronic kidney disease. Noureddin Nourbakhsh, DO He is active in clinical and translational research into acute kidney injury. Elliot Perens, MD, PhD He is interested and active in basic research in developmental nephrology. He obtained fellowship research support from the California Institute of Regenerative Medicine (CIRM) fellowship for and a grant from the A.P. Giannini Foundation in Peter Yorgin, MD He is active in clinical research. He is conducting outcomes studies in pediatric dialysis and lupus nephritis. He is a recognized expert on anemia in chronic kidney disease and is frequently an invited speaker in national meetings. RESEARCH SUPPORT Robert Mak, MD, PhD Abbott (PI) June 2012-May 2014 $178,435 "The impact of atrasentan on protenuria, disease progression, cardiovascular complications and survival in a mouse model of diabetic nephropathy with chronic kidney disease" (PI) Sept 2012-Aug 2014 $136,362 Cystinosis Research Foundation "Inflammation and muscle wasting in nephropathic cystinosis" R24HD050837(PI) June 2013-May 2015 $57,938 NIH Muscle Center Grant "The impact of vitamin D on muscle wasting in chronic kidney disease. Pilot Project" (PI) Jul 2013-June 2015 $148,500 Bioline, Inc Use of leptin receptor antagonists in chronic kidney disease" NIDDK U01 DK (Co-PI) Oct 2013-Sept 2018 $26,540 NIH "Cohort study of chronic kidney disease in children" (PI) Jul 2014-Jul 2015 $206,711 AVEO Pharmaceutical "MIC/GDF-15 in chronic kidney disease" Elliot Perens, MD, PhD (PI) Oct 2014-Sept 2017 $84,666 Binational Science Foundation US-Israel Collaboration Grant "Leptin receptor antagonists ameliorates muscle and renal fibrosis fibrosis in chronic kidney disease" TG (PI) July 2012-June 2015 $213,000 CIRM Training Grant California Institute of Regenerative Medicine Postdoctoral Fellowship Identification of factors regulating kidney cell fate: Hand2 inhibits intermediate mesoderm formation." PUBLICATIONS Gunta SS, Mak RH. Is obesity a risk factor for chronic kidney disease in children? Pediatric Nephrology 28: , Impact factor 2.9. Carter CE, Benador NM. Therapeutic plasma exchange for the treatment of pediatric renal diseases in Pediatric Nephrology 29:35-50, Impact factor 2.9. Gunta SS, Mak RH. Hypertension in children with obesity. World Journal of Hypertension 4:15-24, Ingulli E, Mak RH. Growth in children with chronic kidney disease: role of nutrition, growth hormone, dialysis and steroids. Current Opinion in Pediatrics 26: , Impact factor 2.6. Mak RH, Cheung W, Gertler A. Exploiting the therapeutic potential of leptin signaling in cachexia. Current Opinion in Supportive Palliative Care 8: , Impact factor 1.9. Ding W, Cheung W, Mak RH. Impact of obesity on kidney function and blood pressure in children. World Journal of Nephrology 4: , *Cheung WW, Ding W, Gunta SS, Tabakman R, Klapper LN, Gertler A, Mak RH. A pegylated leptin antagonist ameliorates CKDassociated cachexia in mice. Journal of the American Society of Nephrology 25: , Impact factor 9.5 Lee B, Qiao L, Lu M, Yoo HS, Cheung W, Mak RH, Schaack J, Feng GS, Chi NW, Olfsky J, Shao J. C/EBP regulates macrophage activation and systemic metabolism. American Journal of Physiology Endocrinology and Metabolism 306:E1144-E1154, Impact factor 3.6. Abraham AG, Mak RH, Mitsnefes M, White C, Moxey-Mims M, Warady B, Furth SL. Protein energy wasting in children with chronic kidney disease. Pediatric Nephrology 29: , Impact factor 2.9. Warady BA, Abraham AG, Schwartz GJ, Wong CS, Muñoz A, Betoko A, Mitsnefes M, Kaskel F, Greenbaum LA, Mak RH, Flynn J, Moxey- Mims MM, Furth S. Predictors of Rapid Progression of Glomerular and Nonglomerular Kidney Disease in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort. American Journal of Kidney Disease 65: , Impact factor 5.8. AWARDS & HONORS We were recognized in News and World Report as one of the top Pediatric Nephrology programs in the US: 24 th in 2013, 27 th in 2014 and 38 th in Elizabeth Ingulli, MD Teaching Attending of the Year, UCSD Residents, July 14-June 15 Robert Mak, MD, PhD Editorial Board, Nature Reviews Nephrology, 2009-present Editorial Board, World Journal, 2012 present Editorial Board, World Journal of Hypertension, 2013 present Editorial Board, World Journal of Nephrology, 2013 present Editorial Board, American Academy, PREP Nephrology, 2013-present Editorial Board, Pediatric Research, 2014-present Elliot Perens, MD, PhD ASPN Presentation Award, PAS Annual Meeting, Vancouver, Canada. May Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 231

117 Neurology 232 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 233

118 INTRODUCTION FACULTY The Division of Pediatric Neurology provides comprehensive consultation, assessment, and management of disorders of the brain, spinal cord, nerves and muscles that affect infants, children and adolescents. In addition to general childhood neurological disorders, special areas of expertise among the division members include neurodevelopmental disabilities, (e.g, autism, developmental delay, Rett syndrome), epilepsy, metabolic disorders, brain tumors, neurogenetic disorders, headache, movement disorders, neuromuscular disorders, pediatric stroke, gait disturbances, ataxia, cerebral palsy, and neonatal neurology. Members of the Division are also actively engaged in basic, translational, and clinical research to better understand the mechanisms of brain development and disease, and to advance treatment modalities for children with neurological disorders. The division provides inpatient and outpatient clinical services, including consultations, ongoing care, advice and support regarding neurological issues for the greater San Diego area and contiguous counties. Members of the division also receive referrals for consultations from all parts of the United States and from many other countries around the world. Jeffrey Neul, MD, PhD Professor and Vice Chair of Neuroscience Division Chief Michael Zimbric, MD Associate Clinical Professor of Neurosciences and Pediatrics Clinical Director Jonathan Bui, MD, PhD Assistant Adjunct Professor of Neurosciences John Crawford, MD Associate Adjunct Professor of Neuroscience and Pediatrics Jennifer Friedman, MD Clinical Professor of Neurosciences and Pediatrics DIVISION FAST FACTS Division provides 1,500 Inpatient admissions & consultations per year and 14,000 outpatient services Joseph Gleeson, MD Rady Professor of Neurosciences Jeffrey Gold, MD, PhD Assistant Clinical Professor of Neurosciences Carla Grosmann, MD Associate Clinical Professor of Neurosciences and Pediatrics Richard Haas, MD Professor of Neurosciences and Pediatrics Chamindra Konersman, MD Assistant Professor of Neurosciences MAJOR PLANS AND GOALS Expanding our comprehensive epilepsy program with an emphasis on non-medical management of intractable epilepsy Expanding our neonatal neurology program and are actively recruiting 2 additional neonatal neurologists William Lewis, MD Clinical Professor of Neurosciences Mark Nespeca, MD Clinical Professor of Neurosciences and Pediatrics Michelle Sahagian, MD Assistant Clinical Professor of Neurosciences and Pediatrics Shifteh Sattar, MD Assistant Professor of Neurosciences Eenhancing our interactions with the Rady Pediatric Genomics and Systems Medicine Institute to provide access to advanced genomics and precision medicine for patients in the Child Neurology clinics. Outpatient: We are continuing to develop and expand our specialty clinics in Rett syndrome, Tuberous Sclerosis, and Muscular Dystophy and are developing additional clinics in Angelman Syndrome, Neurofibromatosis and other neurocutaneous disorders, and Complicated Headache Doris Trauner, MD Professor of Neurosciences and Pediatrics Sonya Wang, MD, Assistant Clinical Professor of Neurosciences 234 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 235

119 Natanya Maio, MD Dillon Chen MD, PhD Andrew Ng, MD The Division of Pediatric Neurology has an active outpatient clinic adjacent to RCHSD, and sees over 14,000 patient visits per year. Faculty members also see patients at satellite clinics in Escondido, Encinitas, Murrieta, and Oceanside, California. Inpatient admissions and consultations to the pediatric neurology service number approximately 1,500 per year. In addition to inpatient coverage at RCHSD, the division provides neurologic consultation services to the Neonatal Intensive Care Units at the UCSD Medical Center, Sharp Mary Birch Hospital, and Scripps Mercy Hospital in San Diego. The Clinical Neurophysiology Laboratory provides comprehensive EEG and EMG services and conducts over 2,000 EEGs and 100 EMGs annually. An active inpatient epilepsy monitoring unit provides continuous EEG monitoring for epilepsy patients. Continuous EEG monitoring is provided in the Pediatric Intensive Care Unit and the Neonatal Intensive Care Units as well. Patients with all types of neurological conditions are seen by our faculty. In addition to general neurology clinics, there are a number of specialty clinics at the main site, including autism, intractable epilepsy, headache, movement disorders, neurogenetics, neonatal neurology follow-up, neuromuscular disorders, Rett syndrome, neuro-metabolic, cerebrovascular, neuro-oncology/brain tumor, and neurocutaneous syndrome clinics. Jonathan Bui, MD, PhD Dr. Bui has broad clinical interests with a focus on cerebrovascular disease and behavioral neurology. John Crawford, MD Dr. Crawford is Director of the Pediatric Neuro-oncology program and is a pediatric neuro-oncologist who specializes in diagnosis and management of children with brain tumors. These include children with neuro-cutaneous syndromes such as neurofibromatosis and tuberous sclerosis. He is Principal Investigator of the Pacific Pediatric Neuro-Oncology Consortium. Dr Crawford has interests in clinical and translational neuro-oncology research. Dr. Crawford is the Director of the Pediatric Neurology Training Program. Jennifer Friedman, MD Dr. Friedman is a specialist in movement disorders in children and adults. Her clinical interests include movement disorders (including but not limited to dystonia and Tourette syndrome), neurogenetics and neurometabolic disorders. Joseph Gleeson, MD Dr. Gleeson s clinical interests focus particularly on neurogenetic disorders and parallel his research interests. These included inherited recessive neurodevelopmental disorders, and focal cortical malformations. For both, there are active human subjects protocols for recruitment locally, nationally and internationally. Jeffrey Gold, MD, PhD Dr. Gold is the acting Director of the Neonatal Neurology program. He is a board-certified in pediatric neurology and clinical neurophysiology. His primary research interests and learning and memory, as well as using new technology to detect, prevent, and treat neurologic disease. He also teachers neurology and neuroscience to medical students, graduate students, and residents at UCSD. 236 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report FELLOWS CLINICAL ACTIVITIES Aliya Frederick MD, PhD Aileen Tanaka MD Carla Grosmann, MD Dr. Grosmann specializes in neuromuscular disorders and electromyography. She directed the Muscular Dystrophy Clinic at RCHSD until August of 2014, and then spent 1 year in Baltimore, Maryland as the Wellstone Fellow in Clinical Research in Muscular Dystrophy at the Johns Hopkins School of Medicine and Kennedy Krieger Institute. In July 2015 she received certification from the Bloomberg School of Public Health in the Science of Clinical Investigation (SOCI) program for completion of coursework in Ethics in Clinical Research, Clinical Trial Design, Quantitative Analysis, and Quality Improvement and Knowledge Translation Research. Currently she sees patients with neuromuscular diseases, oversees clinical trials in this area, and participates in the Muscular Dystrophy of America Clinic at RCHSD. Richard Haas, MD Dr. Haas clinical interests include neurometabolic disease, Rett syndrome, neuromuscular disease and neonatal neurology. He directs the UCSD Mitochondrial and Metabolic Disease Center where the research focus is on improving diagnostic testing for mitochondrial disease, the role of mitochondrial DNA in disease and the mitochondrial role in neurodegenerative disease. Chamindra Konersman, MD Dr. Konersman focuses on neuromuscular disorders both at RCHSD and UCSD. She is the director of the MDA clinic at both sites and cares for both children and adults with a range of neuromuscular problems. William Lewis, MD Dr. Lewis has broad clinical interests, and specific interests in pediatric headache syndromes. Mark Nespeca, MD Dr. Nespeca is Medical Director of the EEG Laboratory. He is Board Certified in Pediatrics, Neurology/Child Neurology, Clinical Neurophysiology and Epilepsy. He is an active clinician with interest and expertise is in pediatric electroencephalography and epilepsy. He also has a clinical and research interest in Angelman Syndrome. Jeffrey Neul, MD, PhD Dr. Neul is the Division Chief for Child Neurology and the Vice Chair for Developmental Neurosciences in the Department of Neurosciences. Dr. Neul focuses his clinical work on neurodevelopmental disorders, especially Rett syndrome. He conducts basic, translational, and clinical research in these disorders to develop and test novel therapies. Michelle Sahagian, MD Dr. Sahagian provides consultation and follow-up care for a wide variety of neurological disorders, primarily serving north county San Diego. She also provides neurologic care for children who reside at the Helen Bernardy Center for Medically Fragile Children. Shifteh Sattar, MD Dr. Sattar is the Medical Director of the Epilepsy Surgery Program at RCHSD, and is a board certified neurophysiologist with clinical interest in epilepsy, especially the non-medical approach to intractable epilepsy. Doris Trauner, MD Dr. Trauner has clinical interests encompassing neurodevelopmental disorders, including autistic spectrum disorders, language and neurobehavioral disorders, epilepsy and epileptic behavior syndromes, and neurocutaneous syndromes. Sonya Wang, MD Dr. Wang is a pediatric epileptologist with special interest in epilepsy manifestations in children. The Division runs an ACGME-accredited training program in pediatric neurology in conjunction with the adult neurology training program at UCSD Medical Center and UCSD School of Medicine. Trainees rotate at UCSD Medical Center and the San Diego Veterans Administration Medical Center for adult neurology training, and at RCHSD for pediatric neurology training. An ACGME-approved neurophysiology fellowship is also available in conjunction with the adult neurophysiology training program at UCSD Medical Center. Graduate students and postdoctoral research fellows are also an active part of the divisional teaching activities. Faculty members participate in several graduate programs, including the UCSD Neurosciences Program, the UCSD-SDSU Joint Doctoral Program in Clinical Psychology, the UCSD-SDSU Joint Doctoral Program in Speech-Language Pathology, and the UCSD Graduate Program in Cognitive Science. The division faculty also provides both formal lectures and bedside/ clinic teaching to residents in Pediatrics, Neurology, Psychiatry, Emergency Medicine, and Family Practice and to medical students both in the preclinical and clinical years. An elective rotation that includes both inpatient and outpatient training is open to fourth year medical students. Developmental-Behavioral Pediatrics Fellows spend one month on the child neurology outpatient service during the course of their training. The faculty in pediatric neurology provides daily teaching rounds on the inpatient service at RCHSD, as well as weekly teaching rounds in the three major Neonatal Intensive Care Units for which they provide neurological coverage. Didactic sessions in child neurology include weekly lecture series for child neurology trainees, monthly journal club, monthly noon lecture series for pediatrics house staff and students, monthly case conferences, monthly neuro-radiology rounds, monthly neuropathology conference, monthly quality improvement activities, and yearly lecture series to adult neurology residents and child psychiatry fellows. One of the most recent additions is the establishment of a formal curriculum for Pediatric Neuro-Oncology Rotation for residents and fellows. RESEARCH SUPPORT John Crawford, MD Clinical Trial Protocol 14J-MC-HHBD 07/ /2014 Cost Reimburseable A Phase I Trial of LY in Pediatric Patients with Recurrent or Refractory Rhabdomyossrcoma or Meduloblastoma Jennifer Friedman, MD Michael Zimbric, MD Dr. Zimbric is the clinical director and a general pediatric neurologist with a wide range of interests in clinical neurological disorders affecting children. TEACHING ACTIVITIES Neurology Skills Workshop for Pediatrics Housestaff: This is a newly developed addition to the training of pediatric housestaff. As part of an educational study, pediatric housestaff perform a neurological examination on selected neuro-oncology patients with interesting findings. Following a 15 minute exam, the residents document their findings on a blank progress note. The patient is then examined by a Neurology Attending with the resident and feedback is given. The residents neurological examinations are then analyzed to determine relative strengths and weaknesses in the neurological examination during pediatrics residency. The goal is to track the progress of residents during their entire training period. It is the hope that the project can serve as a model for other pediatric residency programs. Leadership of Educational Programs: John Crawford, MD, Director, Child Neurology Training Program Michael Zimbric, MD, Director, Fourth Year Medical Student Elective John Crawford, MD, Coordinator, Third Year Medical Student Rotations in Pediatric Neurology Richard Haas, MD, Faculty Coordinator, Pediatric Neurology Journal Club Mark Nespeca, MD, Coordinator, monthly Pediatric Neurology lectures for Pediatric housestaff Annual Pediatric Electroencephalography Month Elective for Pediatric Neurology Fellows and Adult Neurology Housestaff Jonathan Bui, MD, Coordinator, Course on Neuroimaging for Housestaff Joseph Gleeson, MD, Initiated an MD/PhD Lunch Series to introduce UCSD students to the outstanding research at the School of Medicine Shifteh Sattar, MD, Epilepsy Surgery Conference RESEARCH ACTIVITIES 07/ /2016 $22,000 UCSD/Rady Tourette Center (Rady Academic Enrichment) NBI /2015 Present $160,915 Neurocrine Biosciences T-Force Study: A Phase 1B, Open-Label, Multiple-Dose Study to Evaluate The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamcis of NBI in Children and Adolescents with Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 237

120 Tourette Syndrome 03/2015 Present $150,000 Stealth BioTherapeutics SPIMM-201/Bendavia Study - A Phase 1/2 Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending-Dose Clinical Study Investigating the Safety, Tolerability, and Efficacy of Intravenous MTP-131 for the Treatment of Mitochondrial Myopathy in Subjects with Genetically Confirmed Mitochondrial Disease Stealth BioTherapeutics SPIMM-201/Bendavia Study Joseph Gleeson, MD R01NS (PI) $617,937 NINDS Molecular Characterization of Hemimegalencephaly HHMI (PI) 04/01/2008-3/31/2018 Negotiated annually Howard Hughes Medical Institute Genetic basis of childhood neurological disorders (PI) )10/01/2010-9/30/2016 $250,000 Simons Foundation Autism Research Initiative Molecular characterization of inbred families with autism and epilepsy P01 HD (PI) 09/01/2011-8/31/2017 $900,000 Developmental Mechanisms of Human Structural Brain Defects Richard Haas, MD (Haas PI) 9/2011-8/2014 $147,558 NIH (North American Mitochondrial Disease Consortium Training Fellowship) (PI) 9/2012-8/2016 $399,575 FDA Dept. of Health and Human Services Phase 2 Study of Levetiracetam for Neonatal Seizures Jeffrey Neul MD PhD 9/2014-8/2019 $1,250,000 NIH U54 HD (Neul Admin Head) Rett Syndrome, MECP2 Duplications, and Rett-related Disorders Natural History R01 HD (PI) 6/2010-5/2016 $1,733,962 NIH (NICHD) Characterization of autonomic dysfunction in Rett syndrome and other MECP2 disorders R21 NS (MPI) 2/2015-1/2016 $394,230 NIH (NINDS) The Nature of Astrocyte Heterogeneity in RTT (PI) $50,000 International Rett Syndrome Foundation #2593 Pharmacological treatment of cardiac rhythm abnormalities in Rett Syndrome (PI) $100,000 International Rett Syndrome Foundation #2901 Creation of a DNA repository for Rett syndrome (PI) $600,000 International Rett Syndrome Foundation #2906 Nonsense suppression as a therapeutic approach to Rett syndrome (PI) $314,456 Rett Syndrome Research Trust Identification of Genetic Modifiers in Rett Syndrome (MPI) $600,000 International Rett Syndrome Foundation UCSD Integrated Read-through Program for Rett Syndrome Sharon Nichols, PhD 5 R01 MH / /2014 $350,017 NIH Memory Functioning in Children and Adolescents with Perinatal HIV Infection (Key Personnel) 08/ /2014 $361,132 5 U01 HD Pediatric HIV/AIDS Cohort Study Initiative (SMARTT Study) (Key Personnel) 08/ /2014 $272,297 5 U01 HD (Spector PI) Pediatric HIV/AIDS Cohort Study Initiative (AMP Study) (Key Personnel) 09/ /2015 $3,286 5 R01 DA (Goodenow PI) Substance Use and Immunity in HIV+ infected Adolescents by Systems Biology (PI) 08/ /2017 $229,157 5 R01 DA (Woods Sub) Targeting PM to Improve HIV Adherence in Adolescents at Risk for Substance Abuse Doris Trauner, MD U01NS (PI) $62,750 NIH (NINDS) Childhood Absence Epilepsy (PI) $56,228 Patient-Centered Outcomes Research Institute (PCORI) (Emory University) Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE) PUBLICATIONS Gold, Crawford JR, Glaser C, Sheriff H, Wang S and Nespeca N. The role of continuous EEG in childhood encephalitis. Ped Neurol. 2014;50: Kool M, Jones DT, Jager N, Northcott AP, Pugh TJ, Hovestadt V, Piro RM, Adriana Esparza LA, Markant SL, Remke M, Milde T, Vourdeaut F, Ryzhova M, Sturm D, Pfaff E, Stark S, Hutter S, Seker- Cin H, Johann P, Bender S, Schmidt C, Rausch T, Shih D, Reimand J, Sieber L, Wittmann A, Linke L, Witt H, Weber JD, Zapatka M, Konig R, Beroukhim R, Bergthold G, van Sluis P, Volckmann R, Koster J, Versteeg R, Schmidt S, Wolf S, Lawrenz C, Bartholomae CC, van Kalle C, Unterberg A, Herold-Mende C, Hofer S, Kulozik AE, von Deimling A, Scheurlen W, Felsberg J, Reifenberger F, Hasselblatt M, Crawford JR, Grant GA, Jabado N, Perry A, Cowdrey C, Croul S, Zadeh G, Korbel JO, Doz F, Delattre O, Bader GD, McCabe MG, Collins VP, Kieran MW, Cho Y-J, Pomeroy SL, Witt O, Brors B, Taylor MD, Schuller U, Korschunov A, Eils R, Wechesler-Reya R, Lichter P, Pfister SM on behalf of the ICGC PedBrain Tumor Project. Genome Sequencing of SHH Medulloblastoma Predicts Age-Dependent Response to Smoothened- Inhibition. Cancer Cell. 2014;25:: Gabel B, Yoon J, Crawford JR. Clinical Isolated Syndrome Mimicking Focal Brainstem Glioma in a Child. BMJ Case Rep Mar 10;2014. Nomura N, Pastorino S, Gymnopoulos M, Pengfe J, Lambert G, Crawford JR, Piccioni D, Juarez T, Pingle SC, Makale M, Kesari S. Prostate specific membrane antigen expression in primary gliomas and breast cancer brain metastasis. Cancer Cell Int :26. doi: / Qaddoumi I, Kocak M, Atmaram SP, Armstrong GT, Wetmore C, Crawford JR, Lin T, Boyett JM, Kun LE, Boop FA, Merchant TE, Ellison DW, Gajjar A, Broniscer A. Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High- Grade Gliomas. Front Oncol Apr 1;4:67. Wong V, Crawford JR. Extensive Subdural Spinal Enhancement Mimicking Leptomeningeal Disease in a Young Child with Posterior Fossa Tumour Following Lumbar Puncture and Surgery. BMJ Case Rep Apr 15;2014. pii: bcr Rao KI, Malicki DM, Crawford JR. Primary Intraventricular Central Nervous System Rhabdomyosarcoma. Pediatr Neurol Jan;52(1): Brun S, Esparza LA, Garcia G, Terry D, Huang J-M, Pavlyukov MS, Li X-N, Grant G, Crawford JR, Levy M, Conway EM, Smith L, Nakano I, Wang Q, Wechsler-Reya RJ. Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma. Oncogene Rao KI, Levy ML, Crawford JR. Giant Suprasellar Arachnoid Cyst Presenting with Precocious Puberty. BMJ Case Rep Aug 19;2014. pii: bcr Rao K, Shayan K, Levy ML, Crawford JR. Giant Pericallosal Lipoma Associated with Epilepsy and Chronic Headaches in a Child. BMJ Case Rep Oct 27;2014. Wong V, Lefloch N, Crawford JR. Fatal Gastrointestinal Haemorrhage in a Young Boy with Newly Diagnosed Metastatic Medulloblastoma on High Dose Dexamethasone. Case Rep Pediatr. 2014;2014: Fogal V, BabicI, Chao Y, Pastorino S, Mukthavaram R, Jiang P, Cho YC, Pingle SC, Crawford JR, Piccioni DE, Kesari S. Mitochondrial p32 is upregulated in Myc expressing brain cancers and mediates glutamine addiction. Oncotarget Jan 20;6(2): Jankowski PP, Crawford JR, Khanna P, Malicki DM, Ciacci JD, Levy ML. Pituitary tumor apoplexy in adolescents. World Neurosurg Dec 17. pii: S (14) [Epub ahead of print]. Bykowski J, Kruk P, Gold JJ, Glaser CA, Sheriff H, Crawford JR. Acute Pediatric Encephalitis Neuroimaging: Single Institution Series as Part of the California Encephalitis Project. Pediatr Neurol Jun;52(6): Rismanchi N, Gold JJ, Sattar S, Glaser C, Sheriff H, Proudfoot J, Mower A, Crawford JR, Nespeca MN, Wang SW. Epilepsy after resolution of presumed childhood encephalitis. Pediatr Neurol Jul;53(1): Chen*, Y., Friedman*, J., Chen*, D., Chan, C. K., Bloss, C. S., Hisama, F. M., Topol, S. E., Carson, A. R., Pham, P.H., Bonkowski, E. S., Scott, E. R., Lee, J. K., Zhang, G., Oliveira, G., Xu, J., Scott-Van Zeeland, A. A., Chen, Q., Levy, S., Topol, E. J., Storm, D., Swanson, P. D., Bird, T. D., Schork, N. J., Raskind, W. H. Torkamani, A. Gain-of- Function ADCY5 Mutations Cause Familial Dyskinesia with Facial Myokymia. Annals of Neurology Apr;75(4): (*these authors contributed equally) Torkamani, A., Bersell, K., Jorge, B., Bjork, R., Friedman, J., Bloss, C., Cohen, J., Gupta, S., Naidu, S., Vanoye, C., George, A., Kearney, J. De Novo KCNB1 Mutations in Epileptic Encephalopathy. Annals of Neurology Oct;76(4): Bloss, C.S., Van Zeeland, A., Darst, B.F., Boeldt, D. L., Erikson, G.A., Bethel, K. Friedman, J.R. Hwynn, N. Patay, B. Pockros, P.J. Scott, E. Simon, R. Williams, G. Schork, N.J. Topol, E. J., Torkamani, A. A Genome Sequencing Program for Novel Undiagnosed Diseases. Genet Med Mar Mar 19. Viollet, L., Glusman, G., Newcomb, T.M., Murphy, K.J., Reyna, S. P., Nelson, B., Sweney, M., Andermann, F., Barbano, R., Brown, C., Chugani, H., Cheyenne, S., Collins, A., DeBrosse, S., Friedman, J., Huff, C., Jorde, L.B., King, M., LaSalle, B., Leventer, R.J., Lewelt, A., Massart, M.B., Merida, M., Rust, R., Scheindlin, B., Zhang, Y., Renault, F., Sotero, M., Tennyson, R., Uldall, P., Zupanc, M., Xin, W., Silver, S., Swoboda, K.J. Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Preliminary Genotype-Phenotype Correlations in 187 subjects from the US AHCF registry. Plos One May 21;10(5):e Friedman, J.R., Meneret, A., Chen, D-H., Trouillard, O., Vidailhet, M., Raskind, W.H., Roze, E. ADCY5 Mutation Carriers Display Pleiotropic Day and Night Time Dyskinesias. Movement Disorders epub ahead of print doi: /mds Maraş Genç H, Uyur Yalçın E, Rosti RÖ, Gleeson JG, Kara B. TSEN54 gene-related pontocerebellar hypoplasia type 2 presenting with exaggerated startle response: report of two cases in a family. Turk J Pediatr May-Jun;57(3): Roosing S, Hofree M, Kim S, Scott E, Copeland B, Romani M, Silhavy JL, Rosti RO, Schroth J, Mazza T, Miccinilli E, Zaki MS, Swoboda KJ, Milisa-Drautz J, Dobyns WB, Mikati MA, İncecik F, Azam M, Borgatti R, Romaniello R, Boustany RM, Clericuzio CL, D'Arrigo S, Strømme P, Boltshauser E, Stanzial F, Mirabelli-Badenier M, Moroni I, Bertini E, Emma F, Steinlin M, Hildebrandt F, Johnson CA, Freilinger M, Vaux KK, Gabriel SB, Aza-Blanc P, Heynen-Genel S, Ideker T, Dynlacht BD, Lee JE, Valente EM, Kim J, Gleeson JG. Functional genome-wide sirna screen identifies KIAA0586 as mutated in Joubert syndrome. Elife May 30;4:e Guemez-Gamboa A, Nguyen LN, Yang H, Zaki MS, Kara M, Ben- Omran T, Akizu N, Rosti RO, Rosti B, Scott E, Schroth J, Copeland B, Vaux KK, Cazenave-Gassiot A, Quek DQ, Wong BH, Tan BC, Wenk MR, Gunel M, Gabriel S, Chi NC, Silver DL, Gleeson JG. Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome. Nat Genet Jul;47(7): Akizu N, Cantagrel V, Zaki MS, Al-Gazali L, Wang X, Rosti RO, Dikoglu E, Gelot AB, Rosti B, Vaux KK, Scott EM, Silhavy JL, Schroth J, Copeland B, Schaffer AE, Gordts PL, Esko JD, Buschman MD, Field SJ, Napolitano G, Abdel-Salam GM, Ozgul RK, Sagıroglu MS, Azam M, Ismail S, Aglan M, Selim L, Mahmoud IG, Abdel-Hadi S, Badawy AE, Sadek AA, Mojahedi F, Kayserili H, Masri A, Bastaki L, Temtamy S, Mu ller U, Desguerre I, Casanova JL, Dursun A, Gunel M, Gabriel SB, de Lonlay P, Gleeson JG. Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosomeautophagosome dysfunction. Nat Genet May;47(5): Faqeih EA, Bastaki L, Rosti RO, Spencer EG, Zada AP, Saleh MA, Um K, Gleeson JG. Novel STAMBP mutation and additional findings in an Arabic family. Am J Med Genet A Apr;167A(4): UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 239

121 Mishra-Gorur K, Çağlayan AO, Schaffer AE, Chabu C, Henegariu O, Vonhoff F, Akgu mu ş GT, Nishimura S, Han W, Tu S, Baran B, Gu mu ş H, Dilber C, Zaki MS, Hossni HA, Rivière JB, Kayserili H, Spencer EG, Rosti RÖ, Schroth J, Per H, Çağlar C, Çağlar Ç, Dölen D, Baranoski JF, Kumandaş S, Minja FJ, Erson-Omay EZ, Mane SM, Lifton RP, Xu T, Keshishian H, Dobyns WB, Chi NC, Šestan N, Louvi A, Bilgu var K, Yasuno K, Gleeson JG, Gu nel M. Mutations in KATNB1 cause complex cerebral malformations by disrupting asymmetrically dividing neural progenitors. Neuron Dec 17;84(6): Kumar R, Corbett MA, Smith NJ, Jolly LA, Tan C, Keating DJ, Duffield MD, Utsumi T, Moriya K, Smith KR, Hoischen A, Abbott K, Harbord MG, Compton AG, Woenig JA, Arts P, Kwint M, Wieskamp N, Gijsen S, Veltman JA, Bahlo M, Gleeson JG, Haan E, Gecz J. Homozygous mutation of STXBP5L explains an autosomal recessive infantile-onset neurodegenerative disorder. Hum Mol Genet Apr 1;24(7): Zaki MS, Selim L, Mansour L, Mahmoud IG, Fenstermaker AG, Gabriel SB, Gleeson JG. Mutations in FA2H in three Arab families with a clinical spectrum of neurodegeneration and hereditary spastic paraparesis. Clin Genet Jul;88(1):95-7. Law R, Dixon-Salazar T, Jerber J, Cai N, Abbasi AA, Zaki MS, Mittal K, Gabriel SB, Rafiq MA, Khan V, Nguyen M, Ali G, Copeland B, Scott E, Vasli N, Mikhailov A, Khan MN, Andrade DM, Ayaz M, Ansar M, Ayub M, Vincent JB, Gleeson JG. Biallelic truncating mutations in FMN2, encoding the actin-regulatory protein Formin 2, cause nonsyndromic autosomal-recessive intellectual disability. Am J Hum Genet Dec 4;95(6): Crow YJ, Zaki MS, Abdel-Hamid MS, Abdel-Salam G, Boespflug- Tanguy O, Cordeiro NJ, Gleeson JG, Gowrinathan NR, Laugel V, Renaldo F, Rodriguez D, Livingston JH, Rice GI. Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia. Neuropediatrics Dec;45(6): Ben-Salem S, Gleeson JG, Al-Shamsi AM, Islam B, Hertecant J, Ali BR, Al-Gazali L. Asparagine synthetase deficiency detected by whole exome sequencing causes congenital microcephaly, epileptic encephalopathy and psychomotor delay. Metab Brain Dis Jun;30(3): Blanco S, Dietmann S, Flores JV, Hussain S, Kutter C, Humphreys P, Lukk M, Lombard P, Treps L, Popis M, Kellner S, Hölter SM, Garrett L, Wurst W, Becker L, Klopstock T, Fuchs H, Gailus-Durner V, Hrabĕ de Angelis M, Káradóttir RT, Helm M, Ule J, Gleeson JG, Odom DT, Frye M. Aberrant methylation of trnas links cellular stress to neuro-developmental disorders. EMBO J Sep 17;33(18): Baek ST, Kerjan G, Bielas SL, Lee JE, Fenstermaker AG, Novarino G, Gleeson JG. Off-target effect of doublecortin family shrna on neuronal migration associated with endogenous microrna dysregulation. Neuron Jun 18;82(6): Marin-Valencia I, Guerrini R, Gleeson JG. Pathogenetic mechanisms of focal cortical dysplasia. Epilepsia Jul;55(7): Guemez-Gamboa A, Coufal NG, Gleeson JG. Primary cilia in the developing and mature brain. Neuron May 7;82(3): Schaffer AE, Eggens VR, Caglayan AO, Reuter MS, Scott E, Coufal NG, Silhavy JL, Xue Y, Kayserili H, Yasuno K, Rosti RO, Abdellateef M, Caglar C, Kasher PR, Cazemier JL, Weterman MA, Cantagrel V, Cai N, Zweier C, Altunoglu U, Satkin NB, Aktar F, Tuysuz B, Yalcinkaya C, Caksen H, Bilguvar K, Fu XD, Trotta CR, Gabriel S, Reis A, Gunel M, Baas F, Gleeson JG. CLP1 founder mutation links trna splicing and maturation to cerebellar development and neurodegeneration. Cell Apr 24;157(3): Mirzaa GM, Vitre B, Carpenter G, Abramowicz I, Gleeson JG, Paciorkowski AR, Cleveland DW, Dobyns WB, O'Driscoll M. Mutations in CENPE define a novel kinetochore-centromeric mechanism for microcephalic primordial dwarfism. Hum Genet Aug;133(8): Romani S, Illi B, De Mori R, Savino M, Gleeson JG, Valente EM. The ciliary proteins Meckelin and Jouberin are required for retinoic aciddependent neural differentiation of mouse embryonic stem cells. Differentiation Mar-Apr;87(3-4): Ismail S, Schaffer AE, Rosti RO, Gleeson JG, Zaki MS. Novel mutation in the fukutin gene in an Egyptian family with Fukuyama congenital muscular dystrophy and microcephaly. Gene Apr 15;539(2): Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GM, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science Jan 31;343(6170): Akizu N, Silhavy JL, Rosti RO, Scott E, Fenstermaker AG, Schroth J, Zaki MS, Sanchez H, Gupta N, Kabra M, Kara M, Ben-Omran T, Rosti B, Guemez-Gamboa A, Spencer E, Pan R, Cai N, Abdellateef M, Gabriel S, Halbritter J, Hildebrandt F, van Bokhoven H, Gunel M, Gleeson JG. Mutations in CSPP1 lead to classical Joubert syndrome. Am J Hum Genet Jan 2;94(1):80-6. Valente EM, Rosti RO, Gibbs E, Gleeson JG. Primary cilia in neurodevelopmental disorders. Nat Rev Neurol Jan;10(1): Thomas S, Wright KJ, Le Corre S, Micalizzi A, Romani M, Abhyankar A, Saada J, Perrault I, Amiel J, Litzler J, Filhol E, Elkhartoufi N, Kwong M, Casanova JL, Boddaert N, Baehr W, Lyonnet S, Munnich A, Burglen L, Chassaing N, Encha-Ravazi F, Vekemans M, Gleeson JG, Valente EM, Jackson PK, Drummond IA, Saunier S, Attié-Bitach T. A homozygous PDE6D mutation in Joubert syndrome impairs targeting of farnesylated INPP5E protein to the primary cilium. Hum Mutat Jan;35(1): Rosti RO, Sadek AA, Vaux KK, Gleeson JG. The genetic landscape of autism spectrum disorders. Dev Med Child Neurol Jan;56(1):12-8. Bronstein JM, Paul K, Yang L, Haas RH, Shults CW, Le T, Ritz B. Platelet mitochondrial activity and pesticide exposure in early Parkinson's disease. Mov Disord May;30(6): Haas RH, Zolkipli Z. Mitochondrial disorders affecting the nervous system. Semin Neurol Jul;34(3): Golomb BA, Erickson LC, Scott-Van Zeeland AA, Koperski S, Haas RH, Wallace DC, Naviaux RK, Lincoln AJ, Reiner GE, Hamilton G. Assessing bioenergetic compromise in autism spectrum disorder with 31P magnetic resonance spectroscopy: preliminary report. J Child Neurol Feb;29(2): Milone M, Klassen BT, Landsverk ML, Haas RH, Wong LJ. Orthostatic tremor, progressive external ophthalmoplegia, and Twinkle. JAMA Neurol Nov;70(11): Gold JJ, Crawford JR, Glaser C, Sheriff H, Wang S, Nespeca M. The role of continuous electroencephalography in childhood encephalitis. Pediatr Neurol Apr;50(4): Rismanchi N, Gold JJ, Sattar S, Glaser CA, Sheriff H, Proudfoot J, Mower A, Crawford JR, Nespeca M, Wang SG. Epilepsy After Resolution of Presumed Childhood Encephalitis. Pediatr Neurol Jul;53(1): Pitcher MR, Ward CS, Arvide EM, Chapleau CA, Pozzo-Miller L, Hoeflich A, Sivaramakishnan M, Saenger S, Metzger F, Neul JL. Metabolic syndrome in mice lacking MeCP2 function is worsened by insulinotrophic treatments. Molecular Human Genetics. (2013) 22: Suter B, Treadwell-Deering D, Zoghbi HY, Glaze DG, Neul JL. Brief Report: MECP2 Mutations in People Without Rett Syndrome. J Autism Dev Disord Aug 7. PMID: PMCID: PMC Cuddapah VA, Pillai RB, Shekar KV, Lane JB, Motil KJ, Skinner SA, Tarquinio DC, Glaze DG, McGwin G, Kaufmann WE, Percy AK, Neul JL*, Olsen ML*. Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome. J Med Genet. 10(3):e PMID: Wangler MF, Gonzaga-Jauregui C, Gambin T, Penney S, Moss T, Chopra A, Probst FJ, F, Yang Y, Werlin S, Eglite I, Kornejeva L, Bacino CA, Baldridge D, Neul JL, Lehman EL, Larson A, Beuten J, Muzny DM, Jhangiani S, Baylor-Hopkins Center for Mendelian Genomics, Gibbs RA, Lupski JR, Beaudet A. Heterozygous De Novo and Inherited Mutations in the Smooth Muscle Actin (ACTG2) Gene Underlie Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome. PLOS Genetics. Mar 27;10(3):e Neul JL, Lane JB, Lee HS, Geerts S, Barrish JO, Annese F, Baggett LM, Barnes K, Skinner SA, Motil KJ, Glaze DG, Kaufmann WE, Percy AK. Developmental delay in Rett syndrome: data from the natural history study. J Neurodev Disord. 6(1):20. Motil KJ, Barrish JO, Neul JL, Glaze DG. Low bone mineral mass is associated with decreased bone formation and diet in girls with rett syndrome. J Pediatr Gastroenterol Nutr. (2014) 59(3): Glasgow SM, Zhu W, Stolt CC, Huang TW, Chen F, LoTurco JJ, Neul JL, Wegner M, Mohila C, Deneen B. Mutual antagonism between Sox10 and NFIA regulates diversification of glial lineages and glioma subtypes. Nat Neurosci. (2014) 17(10): PMID: Killian JT, Lane JB, Cutter GR, Skinner SA, Kaufmann WE, Tarquinio DC, Glaze DG, Motil KJ, Neul JL, Percy AK. Pubertal Development in Rett Syndrome Deviates From Typical Females. Pediatr Neurol. (2014) 51(6): PMID: Pitcher MR, Herrera JA, Buffington SA, Kochukov MY, Merrit JK, Fisher AR, Schanen NC, Costa-Mattioli M, Neul JL. Rett Syndrome like phenotypes in the R255X Mecp2 mutant mouse are rescued by MECP2 transgene. Hum Mol Genet. (2015)24(9): Herrera JA, Ward CS, Pitcher MR, Kaufmann WE, Skinner S, Percy AK, Glaze DG, Wehrens XHT, Neul JL. Treatment of cardiac arrhythmias in Rett syndrome with sodium channel blocking antiepileptic drugs. Disease Models and Mechanisms. (2015) 8(4): Neul JL, Glaze DG, Percy AK, Feyma T, Beissang A, Dihn T, Suter B, Anagnostou E, Snape M, Horrigan J, Jones NE. Improving Treatment Trial Outcomes for Rett Syndrome: the development of Rett-specific anchors for the Clinical Global Impression Scale. J. Child Neurology. Apr 20 (2015). pii: [Epub ahead of print] Tarquinio DC, Hou W, Neul JL, Lane J, Barnes KV, O Leary HM, Bruck NM, Kaufmann WE, Motil KJ, Glaze DG, Skinner SA, Annese F, Baggett L, Barrish JO, Geerts SP, Percy AK. Age of Diagnosis in Rett Syndrome: Patterns of Recognition Among Diagnosticians and Risk Factors for Late Diagnosis. Pediatric Neurology. (2015) 52(6): Wang J, Wegener J, Huang TW, Smitha Sripathy, De Jesus-Cortes H, Xu P, Tran S, Knobbe W, Leko V, Britt J, Starwalt R, McDaniel L, Ward C, Parra D, Newcomb B, Lao U, Flowers D, Cullen S, Jorstad NL, Yang Y, Glaskova L, Vigneau S, Kozlitina J, Reichardt S, Reichardt H, Gärtner J, Bartolomei MS, Fang M, Loeb K, Keene CD, Bernstein I, Goodell M, Brat DJ, Huppke P*, Bedalov A*, Pieper AA*, Neul JL*. Wild type microglia do not arrest pathology in mouse models of Rett syndrome. Nature. (2015) 521(7552):E1-4. * Co-corresponding authors Neul JL, Sahin M. Therapeutic Advances in Autism and Other Neurodevelopmental Disorders. Neurotherapeutics Jul;12(3): Yousefian O, Ballantyne AO, Doo A, Trauner DA. Clock drawing in children with perinatal stroke. Pediatr Neurol Jun;52(6): Trauner DA. Behavioral correlates of epileptiform abnormalities in autism. Epilepsy Behav Jun;47: Miller M, Chukoskie L, Zinni M, Townsend J, Trauner D. Dyspraxia, motor function and visual-motor integration in autism. Behav Brain Res Aug 1;269: Trauner DA, Lo W. Big strokes for little folks. Neurology Mar 4;82(9): Gold JJ, Trauner DA. Hippocampal volume and memory performance in children with perinatal stroke. Pediatr Neurol Jan;50(1): Mulligan CK, Trauner DA. Incidence and behavioral correlates of epileptiform abnormalities in autism spectrum disorders. J Autism Dev Disord Feb;44(2): Trauner DA, Eshagh K, Ballantyne AO, Bates E. Early language development after peri-natal stroke. Brain Lang Dec;127(3): Viltz L, Trauner DA. Effect of age at treatment on cognitive performance in patients with cystinosis. J Pediatr Aug;163(2): Gold JJ, Crawford JR, Glaser C, Sheriff H, Wang S, Nespeca M. The role of continuous electroencephalography in childhood encephalitis. Pediatr Neurol Apr 19; 50(4): Yinyan Wang, Tianyi Qian, Gan You, Xiaoxia Peng, Clark Chen, Yongping You, KunYao, Chenxing Wu, Jun Ma, Zhiyi Sha, Sonya Wang, Tao Jiang. Localizing seizure-susceptible brain regions associated with low grade gliomas using voxel-based lesionsymptom mapping. Neuro-Oncology July 15; 0, 1 7, doi: /neuonc/nou130. Rismanchi N, Gold JJ, Sattar S, Glaser C, Sheriff H, Proudfoot J, Mower A, Crawford JR, Nespeca M, Wang SG. Epilepsy after resolution of presumed childhood encephalitis. Pediatric Neurology July Vol 53 (1): JR Crawford. HHV-6 and Cancer, HUMAN HERPESVIRUS-6A & 6B In: A clinical Diagnostic Handbook. Third Edition, Louis, Flammand Ed. Academic Press/Elsevier. Levy ML, Crawford JR, Reeves A, Abbasifard S, Altimimi M. Pediatric Neurosurgery: Endoscopic Third Ventriculostomy In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Hong D, Reeves A. Pediatric Neurosurgery: Slit Ventricle Syndrome In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 241

122 Levy ML, Crawford JR, Reeves A. Pediatric Neurosurgery: Endoscopic Cerebellar Medulloblastoma In: 100 Case Reviews in Neurosurgery. Raul Jandial Ed. Elsevier, Levy ML, Crawford JR, Reeves A, Abbasifard S. Pediatric Neurosurgery: Brainstem Glioma In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Reeves A, Abbasifard S. Pediatric Neurosurgery: Hypothalamic Hamartoma In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Reeves A, Altimimi M. Pediatric Neurosurgery: Pilocytic Astrocytoma In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Levy ML, Crawford JR, Altimimi M. Pediatric Neurosurgery: Spasticity In: 100 Case Reviews in Neurosurgery. Raul, Jandial Ed. Elsevier, Friedman, J and Opladen. T. L-Dopa Responsive Dystonia Syndromes. In Congenital Neurotransmitter Disorders: A clinical approach. Georg F. Hoffmann and Nenad Blau (eds). Nova Scientific Publishers Inc. (2014) New York. Jeffrey Neul, MD, PhD National Institute of Health, Neurological Sciences Training (NST- 1) Study Section, standing member National Institute of Health, Molecular Neurogenetics Study Section, standing member Doris Trauner, MD Elected to AOA Medical Honor Society, VCU/MCV School of Medicine, June 2013 America s Top Doctors, Best Doctors in America, top 1%, US News and World Report, 2013 American Academy of Neurology Alliance Awards Committee, 2009-present Cure Cystinosis International Registry Medical Advisory Board, 2011-present AWARDS John Crawford MD, MS Junior Faculty Teaching Award Department of Neurosciences, University of California, San Diego, 2013 Junior Faculty Teaching Award Department of Neurosciences, University of California, San Diego, 2014 Senior Faculty Teaching Award Department of Neurosciences, University of California San Diego, 2015 Leonard Tow Humanism Award in Medicine Nominee, 2015 Top Pediatric Neurologist San Diego Magazine, 2015 Jennifer Friedman, MD Junior Faculty Teaching Award Department of Neurosciences, University of California, San Diego, 2013 Joseph Gleeson, MD 2014 Elected member, Dana Alliance 2014 Elected member, Assoc Amer Physicans 2014 Elected member, Institute of Medicine, National Academy of Sciences Carla Grosmann, MD CureCMD (Congenital Muscular Dystrophy) Physician Outreach Committee Member Present Sarepta Advisory Committee Biogen Idec: SMA Operating Model Advisory Board Meeting AAN Muscular Dystrophy Measure Development Work Group Richard Haas, MD Editor, European Journal of Child Neurology Editorial Boards of the journal Mitochondrion and Journal of Rare Disorders Mark Nespeca, MD Best Doctors in America, Chairman, Professional Advisory Board Epilepsy Foundation of America, San Diego Affiliate Vice Chairman of Programs, Board of Directors Epilepsy Foundation of America, San Diego Affiliate Member, Scientific Advisory Committee Angelman Syndrome Foundation Member, American Epilepsy Society, Self Assessment Exam Advisory Committee 242 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 243

123 Residency Program 244 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 245

124 INTRODUCTION Mission: To train residents to become leaders in the practice of general and subspecialty pediatric medicine. Goal: To train tomorrow s pediatricians, with an emphasis on excellence in patient care, the refinement of critical thinking skills, the acquisition of advanced technical skills, the integration of research into practice, and the development of life-long learning skills. Our program is unique in its exposure to a large and diverse pediatric population with breadth in general and subspecialty medicine, placing special emphasis on community pediatrics, behavioral pediatrics, academic/research pediatrics, and border health. During the three years of training, the resident will evolve progressively with increasing knowledge and responsibility in all aspects of general pediatric medicine. Our UCSD residents participate in a variety of programs for continued intellectual growth. Multiple didactic opportunities are incorporated into the curriculum to enhance resident development and training. Our program recognizes the importance of close supervision and mentorship with a goal to develop a close relationship between the house staff and faculty. Continued opportunities in career development are fostered with exposure to academic and community resources, allowing the resident to gain the tools to advance their careers. Additionally, exciting new growth has occurred in the department to expand resident exposure to Global Health, advocacy training and quality improvement. FACULTY The Community Pediatrics rotation exposes the resident to the important role pediatricians now play in the community. This includes interacting with local schools and child care centers (both as a consultant and on behalf of patients), advocating for child health issues and collaborating with professionals from other disciplines that also care for children. The PL-2 year builds on the experiences of the first year with emphasis on patient management and triage of the ill child. The PL-2 resident rotates through the inpatient ward at RCHSD and experiences increased independence and decision-making. Additionally, the second year resident rotates one month in the Pediatric Intensive Care Unit at RCHSD gaining experience evaluating and managing critically-ill children. The resident continues to have emergency room experience evaluating acutely ill children during the PL-2 year. One month of the second year is dedicated to the care of patients in developmental-behavioral pediatrics. Three to four months of elective time is available in the PL-2 year to enhance exposure to subspecialty medicine, and to allow resident independent time to pursue scholarly works in research or global projects. The PL-3 year provides each resident the opportunity to enhance skills and knowledge in a wide variety of pediatric areas. The senior residents serve as supervisors and teachers to first year residents and medical students. On the inpatient wards at RCHSD, they supervise all admissions to the teaching service and train interns and medical students. Morning Report serves as a forum for in-depth discussion about patient management with subspecialists, general pediatricians and community physicians. The role of teacher extends to the outpatient clinic and emergency room, as well. The PL-3, in close consultation with attending physicians, oversees the care of clinic patients and provides guidance and expertise in general pediatrics. The Emergency Room at RCHSD enhances the senior resident s proficiency in managing acutely ill children. Additional expertise in the care and stabilization of critically ill children is provided through another rotation in the PICU in the third year and by working on the transport team. During the NICU rotation the PL-3 resident serves as a supervising resident to the resident service. The year is rounded out with several elective months to augment each resident s education. There are two to three PL-4 chief residents who serve as instructors in the Department and as representatives of the Chairman of the department. They also act as general pediatric consultants to the residents and to other services. The chief residents organize teaching conferences at UCSD and RCHSD. They also are attending physicians in the inpatient wards. This year is designed to continue to augment general pediatric knowledge through consultation, research, teaching and patient care. Mark H. Sawyer, MD Program Director Christopher Cannavino, MD Associate Program Director RESEARCH ACTIVITIES PROGRAM ADMINISTRATION The PL-1 is expected to take full initiative in the workup and management of patients under the guidance of a supervising resident and attending physician. Intensive exposure is provided to ill children and to children with normal birth, growth and development. During the first year, inpatient pediatrics is taught at RCHSD. The pediatric house officer cares for children with a large variety of pediatric problems, ranging from uncomplicated illnesses to complex diseases with multiple organ involvement. In the PL-1 year, residents also participate in the stabilization and care of the sick neonate. The Neonatal Intensive Care Unit (NICU) at UCSD Allison Reinhardt, Residency Program Administrator Joanne Albrecht, Residency Program Assistant TEACHING ACTIVITIES has a busy delivery service and is a Level III nursery that receives transports of critically ill babies from around San Diego County. The first year resident also spends one month in the Newborn Nursery at UCSD learning to care for normal newborns and common problems appropriate for a general pediatrician. The outpatient experience is varied during the first year and exposes residents to many facets of ambulatory care including emergency medicine, adolescent medicine, general pediatrics and developmental and community pediatrics. Chen DY and Crawford JR. Hodgkin s lymphoma in an adolescent previously treated with surgical resection of third ventricular juvenile pilocytic astrocytoma. BMJ Case Rep 2015 Jun 25:2015 pii:bcr Doi: /bcr Chen DY, Aristizabal P, Crawford JR. Preoperative presentation of a variant of cerebellar mutism syndrome in a young boy with juvenile pilocytic astrocytoma. Pediatr Neurol 2015; 53(3):266-7 Meixel A, Yanchar E, Fugh-Berman A. Hypoactive sexual desire disorder: inventing a disease to sell low libido. J Med Ethics 2015;41: Tompane T, Leong CW, Bush R, Chuang NA, Dansky T, Huang JS. Appropriateness of radiology procedures performed in children with gastrointestinal symptoms and conditions. Clin Gastroenterol Hepatol Jun;12(6): Epub 2013 Sep 11. Guemez-Gamboa A, Coufal NG, Gleeson JG. Primary cilia in the developing and mature brain. Neuron, 2014 May 7. Juan Chapparo; Erin Murphy; Christopher Davis; Rolando M. Viani; Alice Pong. Chest Pain and Shortness of Breath in a Previously Healthy Teenager. Journal of Pediatric Infectious Diseases Society, 2014 May 3. Schaffer AE, Eggens VR, Caglayan AO, Reuter MS, Scott E, Coufal NG, Silhavy JL, Xue Y, Kayserili H, Yasuno K, Rosti RO, Abdellateef M, Caglar C, Kasher PR, Cazemier JL, Weterman MA, Cantagrel V, Cai N, Zweier C, Altunoglu U, Satkin NB, Aktar F, Tuysuz B, Yalcinkaya C, Caksen H, Bilguvar K, Fu XD, Trotta CR, Gabriel S, Reis A, Gunel M, Baas F, Gleeson JG. CLP1 founder mutation links trna splicing and maturation to cerebellar development and neurodegeneration. Cell, 2014 Apr 24. Dunmire SK, Odumade OA, Porter JL et al. Primary EBV infection induces an expression profile distinct from other viruses but similar to hemophagocytic syndromes. PLoS One 2014;9(1):e85422 doi: /journal.pone Balfour HH, Odumade OA, Schmeling DO et al. Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis 2013; 207:80-8. Renuart AJ, Goldfarb DM, Mokomane M, Tawanana EO, Narasimhamurthy M, et al. (2013) Microbiology of Urinary Tract Infections in Gaborone, Botswana. PLoS ONE 8(3): e Moore RK, Grinspan LT, Jimenez J et al. HCM-linked 160E cardiac troponin T mutation causes unique progressive structural and molecular ventricular remodeling in transgenic mice. J Mol Cell Cardiol 2013;58: UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 247

125 Respiratory Medicine 248 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 249

126 INTRODUCTION FACULTY The Division of Respiratory Medicine is dedicated to improving all aspects of respiratory health affecting infants, children, and young adults. The Division has maintained a national ranking in Pulmonology in the U.S. News and World Report survey of children s hospitals since Many of the senior faculty are internationally recognized. The clinical programs provide expert consultation, clinical management expertise, and patient and family education to children and youth with respiratory and sleep disorders in San Diego and surrounding counties, and receive referrals from throughout the U.S. and other countries. The divisional research programs range from fundamental basic investigations regarding the effect of disordered respiration, hypoxia and hypercapnia on cell function and cell fate in brain, heart and lung, to cutting-edge basic research in pulmonary fibrosis, lung development and cystic fibrosis, and novel clinical research studies in cystic fibrosis. Divisional scholars provide research training and mentorship to future investigators from the undergraduate to junior faculty levels. The Division of Respiratory Medicine is critical to the educational mission of the Department, with a well-regarded Pulmonology Fellowship program with outstanding clinical and research training, and programs specific to students, housestaff, fellows and the San Diego practice community. Dr. Lesser organizes a monthly Western states Pediatric Pulmonary Teleconference case discussion series which now includes Respiratory Medicine programs throughout the U.S. and several Canadian Provinces, to improve care of complex patients, and provide education and networking for subspecialty residents and junior faculty in Respiratory Medicine throughout North America. James S. Hagood, MD Professor Division Chief Kathryn Akong, M.D. Assistant Adjunct Professor Priti Azad, PhD Assistant Project Scientist Rakesh Bhattacharjee, MD Associate Professor Mateja Cernelc-Kohan, MD Assistant Professor $3.2 Million in Major Research Grants DIVISION HIGHLIGHTS Division is part of the Childhood Interstitial Lung Disease (ChILD) Research Network Gabriel Haddad, MD Distinguished Professor of Pediatrics & Neuroscience Chairman, Dept Daniel J. Lesser, MD Associate Professor Meerana Lim, MD Professor Mark Pian, MD Professor Paul M. Quinton, PhD Professor and Nancy Olmstead Chair, Pediatric Pulmonary Research MAJOR PLANS AND GOALS The Division of Respiratory Medicine is recruiting additional clinical and research faculty to complement the existing exceptional faculty, optimize access, synergize with our existing exceptional research programs, and strengthen our educational programs. Julie Ryu, MD Professor A.K.M. Shamsuddin, PhD Assistant Project Scientist David K. Shellington, MD Assistant Adjunct Professor Tsering Stobdan, PhD Assistant Project Scientist Simon Wong, MD Associate Project Scientist The Division will work closely with the Rady Pediatric Genomics and Systems Medicine Institute to provide state of the art personalized and precision medicine for our patients. Dr. Ryu is working with the Genomics Institute and Rady Children s Hospital to optimize electronic medical records for accurate and uniform data capture throughout the health care system. The Sleep Disorders Program will be expanding capacity for diagnosis and management of the full spectrum of childhood sleep disorders. Hang Yao, PhD Associate Project Scientist Jin Xue, M.D., PhD Associate Project Scientist Huiwen Zhao, PhD Assistant Project Scientist Dan Zhou, PhD Associate Project Scientist 250 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 251

127 Marilynn Chan, M.D. Divya Chhabra, M.D. Elizabeth Duong, M.D. Erilynn Heinrichsen, Ph.D. 252 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report FELLOWS Taylor Inman, M.D. Sergio Mora Castilla, PhD Tzu-Pin Shentu, PhD TEACHING ACTIVITIES The faculty in the Division are committed to education at all levels, from high school students from disadvantaged backgrounds doing research internships and clinical shadowing experiences, to postdoctoral and international scholars doing advanced basic research projects. Our Fellowship Program in Pediatric Pulmonology is committed to training future generations of scholars to advance respiratory science and transform clinical care. We have recruited exceptional trainees, who are engaged in exciting research projects in microbiome, epigenomics, and bioinformatics. Two of our fellows have received prestigious Pediatrics Scientist Development Program (PSDP) Awards. We are committed to promoting the best evidence-based and physiology-based care for children with respiratory disorders by educating residents in inpatient and outpatient settings, and by providing continuing education to physicians in the communities we serve. The Division s research activities comprise a rich and diverse portfolio of the most advanced and innovative respiratory science, from fundamental cellular and molecular investigations of ion flux, hypoxia signaling, and cell phenotype regulation, to preclinical models of lung disease and innovative therapeutics, to genomic and integrated multi-platform systems biology approaches to elucidate mechanisms of adaptation to hypoxia, lung development, and fibroproliferation. James S. Hagood, MD, the Division Chief, studies the molecular regulation of fibroblast phenotypes in pulmonary fibrotic disease and lung alveolarization. He also studies the roles and regulation of Thy-1, a critical modulator of cellular phenotype, and epigenetic/ epigenomic alterations in lung development and disease, and targeted therapy for diffuse lung diseases. Gabriel G. Haddad, MD, studies the role of ion channels in nerve cells in a low O2 environment. He is also interested in the genetics of susceptibility or tolerance to low or high O2 and the role of gene expression in excitable tissues. He also studies obstructive sleep apnea and the role of hypoxia and hypercapnia on growth and development. Kathryn Akong, MD, PhD, carries out clinical and translational research investigating new therapeutics for cystic fibrosis. Priti Azad, PhD, studies mechanisms by which intermittent (e.g., obstructive sleep apnea and sickle cell anemia) and constant hypoxia (e.g., asthma) lead to cell injury and morbidity or adaptation and survival using Drosophila as well as cell culture model systems. Mateja Cernelc-Kohan, MD studies the role of extracellular microvesicles in pulmonary fibrosis Daniel Lesser, MD, is involved in clinical research investigating the role of sleep disordered breathing in metabolic disease, and lung clearance index in children with neuromuscular disease. Paul M. Quinton, PhD investigates the effects of the genetic defects in fluid and electrolyte transport in cystic fibrosis on pathophysiology in the airways, intestine, and sweat glands in cystic fibrosis and related diseases. Julie Ryu, MD studies innovative methodologies including remote monitoring of asthma management and optimizing the electronic medical record for clinical research. RESEARCH ACTIVITIES A.K.M. Shamsuddin, PhD studies β-adrenergic sweat stimulation, sweat diagnostic testing and electrolyte transport across normal and cystic fibrosis sweat gland and native small and large airway (pigs and humans) epithelia. Simon Wong, PhD studies novel therapeutic modalities and therapeutic targeting in animal models of lung fibrosis, as well as possible therapeutic roles of microvesicles in lung fibrosis. Jin Xue, MD, PhD studies the genetic and molecular basis of sodium hydrogen exchanger isoform 1 (NHE1)-mediated cardiac injury. Hang Yao, PhD studies the cellular and molecular mechanisms of penumbral cell death in focal cerebral ischemia. Huiwen Zhao, PhD, studies mechanisms of hypoxia adaptation using induced pluripotent stem cells-derived neurons obtained from patients with chronic mountain sickness Dan Zhou, PhD, studies the genetic and molecular mechanisms underlying susceptibility and tolerance to hypoxia and hyperoxia in model organisms and humans. RESEARCH SUPPORT Kathryn Akong, MD PhD Cystic Fibrosis Foundation PACE (Program for Adult Care Excellence) April 2015-March 2018 $25,000 Gabriel Haddad, MD 5PO1 HL (PI) July 2010-June 2015 $1,481,795 NIH "Molecular mechanisms of hypoxia tolerance and susceptibility" James S. Hagood, MD R01 HL (PI) July 2012 June 2017 $244,417 NIH/NHLBI "Targeting the Apoptosis-Resistant Pulmonary Myofibroblast" R01 HL (PI) July 2012 June 2016 $129,818 NIH/NHLBI " Targeting the Apoptosis-Resistant Pulmonary Myofibroblast " Carmen Taype Postdoctoral Fellow R01 HL (PI) August 2007 July 2018 $218, 423 NIH/NHLBI "Regulation of Fibroblast Phenotype in Lung Fibrosis" UO1 HL (MPI) May 2014 March 2019 $169,167 NIH/NHLBI "Alveolar DevMap" P01 HL (Project-PI) Sep 2014 August 2019 $165,000 NIH/NHLBI "Novel targeted therapies for pulmonary fibrosis" July 2012 June 2014 $50,000 Pulmonary Fibrosis Foundation "Extracellular Vesicles Alter Cell Phenotype in Pulmonary Fibrosis" AWD (PI) May 2014 April 2015 $50,000 Rady Children s Hospital Academic Enrichment Fund "Data-driven Rare Lung Disease Research at RCHSD" Mateja Cernelc-Kohan, MD T32HL July 2013 June 2014 T32 in Respiratory Biology (Frank Powell, PI) Postdoctoral Fellowship Grant Meerana Lim, MD July 2014 June 2015 $56,750 Cystic Fibrosis Foundation "Cystic Fibrosis Care Center" Paul Quinton, PhD April 2008 July 2016 $75,000 Cystic Fibrosis Foundation "Mucus Release and HCO3- Secretion in Small Airways" January 2015 December 2015 $119,785 Cystic Fibrosis Foundation Therapeutics "Pharmacology of CFTR Correctors and Potentiators in the Native Human Sweat Duct" A K M Shamsuddin, Ph.D. January 2014-December 2015 $120,000 Cystic Fibrosis Research Inc. (CFRI) New Horizon Research Grant Awarded to determine ion transport properties in human native small airways. PUBLICATIONS Aggarwal DD, Rashkovetsky E, Michalak P, Cohen I, Ronin Y, Zhou D, Haddad GG, Korol AB. Experimental evolution of recombination and crossover interference in Drosophila caused by directional selection for stress-related traits. BMC Biol. 13(1):101, Blackwell TS, Tager AM, Borok Z, Moore BB, Schwartz DA, Anstrom KJ, Bar-Joseph Z, Bitterman P, Blackburn MR, Bradford W, Brown KK, Chapman HA, Collard HR, Cosgrove GP, Deterding R, Doyle R, Flaherty KR, Garcia CK, Hagood JS, Henke CA, Herzog E, Hogaboam CM, Horowitz JC, King TE Jr, Loyd JE, Lawson WE, Marsh CB, Noble PW, Noth I, Sheppard D, Olsson J, Ortiz LA, O'Riordan TG, Oury TD, Raghu G, Roman J, Sime PJ, Sisson TH, Tschumperlin D, Violette SM, Weaver TE, Wells RG, White ES, Kaminski N, Martinez FJ, Wynn TA, Thannickal VJ, Eu JP. Future directions in idiopathic pulmonary fibrosis research. An NHLBI workshop report. Am J Respir Crit Care Med Jan 15;189(2): doi: /rccm WS. PMID: Corriden R, Self T, Akong-Moore K, Nizet V, Kellam B, Briddon SJ, Hill SJ. Adenosine-A3 receptors in neutrophil microdomains promote the formation of bacteria-tethering cytonemes. EMBO Rep. 14(8):726-32, 2013 Douglas RM, Bowden K, Pattison J, Peterson AB, Juliano J, Dalton ND, Gu Y, Alvarez EA, Peterson KL, Witztum JL, Haddad GG, Li AC. Intermittent Hypoxia and Hypercapnia induces Pulmonary Artery Atherosclerosis and Right Ventricular Dysfunction in Low Density Lipoprotein Receptor Deficient Mice. J Appl Physiol Dec;115(11): PMCID:PMC Ebrahim M, Hagood JS, Moore J, El-Said H.Bronchoscopic guidance of endovascular stenting limits airway compression. Catheter Cardiovasc Interv Dec 13. doi: /ccd [Epub ahead of print] PMID: Gan Z, Wang J, Salomonis N, Stowe JC, Haddad GG, McCulloch AD, Altintas I, Zambon AC. MAAMD: a workflow to standardize metaanalyses and comparison of affymetrix microarray data BMC Bioinformatics Mar 12;15:69. PMID: Gersten M, Zhou D, Azad P, Haddad GG, Subramaniam S. Wnt Pathway Activation Increases Hypoxia Tolerance during Development. PLoS ONE 9(8):e103292, Gonzalez DJ, Corriden R, Akong-Moore K, Olson J, Dorrestein PC, Nizet V. N-terminal ArgD peptides from the classical Staphylococcus aureus Agr system have cytotoxic and proinflammatory activities. Chem Biol. 21(11): , 2014 Griesi-Oliveira K, Acab A, Gupta AR, Sunaga DY, Chailangkarn T, Nicol X, Nunez Y, Walker MF, Murdoch JD, Sanders SJ, Fernandez TV, Ji W, Lifton RP, Vadasz E, Dietrich A, Pradhan D, Song H, Ming GL, Gu X, Haddad GG, Marchetto MC, Spitzer N, Passos-Bueno MR, State MW, Muotri AR. Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons. Mol Psychiatry PMID: Gu XQ, Pamenter ME, Siemen D, Sun X, Haddad GG. Mitochondrial but not plasmalemmal BK channels are hypoxia-sensitive in human glioma. Glia, (4): PMID: Kurland G, Deterding RR, Hagood JS, Young LR, Brody AS, Castile RG, Dell S, Fan LL,, Hamvas A, Hilman BC, Langston C, Nogee LM, Redding GJ, on behalf of the child Research Network. An Official ATS Clinical Practice Guideline: Classification, Evaluation, and Management of Childhood Interstitial Lung Disease (child) in Infancy. Am J Respir Crit Care Med Aug 1;188(3): Hamvas A, Deterding R, Balch WE, Schwartz DA, Albertine KH, Whitsett JA Cardoso WV, Kotton DK, Kourembanas S, Hagood JS. Diffuse Lung Disease in Children: Summary of a Scientific Conference. Pediatr Pulmonol Apr;49(4): doi: / ppul Hagood JS. Beyond the Genome: Epigenetic Mechanisms in Lung Remodeling. Physiology May 1 Vol. 29 No ; doi: /physiol Harris WT, Kelly DR, Zhou Y, Wang D, Macewen M, Hagood JS, Clancy JP, Ambalavanan N, Sorscher EJ. Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. PLoS One Aug 12;8(8):e doi: /journal.pone PMID: Hartley I, Elkhoury FF, Heon Shin J, Xie B, Gu X, Gao Y, Zhou D, Haddad GG. Long-lasting changes in DNA methylation following short-term hypoxic exposure in primary hippocampal neuronal cultures. PLoS ONE 8(10):e77859, Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 253

128 Heinrichsen ET, Zhang H, Robinson JE, Ngo J, Diop S, Bodmer R, Joiner WJ, Metallo CM, Haddad GG. Metabolic and transcriptional response to a high-fat diet in Drosophila melanogaster. Mol Metab Oct 23;3(1): PMID: Huang H, Lu-Bo Y, Haddad GG. A Drosophila ABC transporter regulates ROS and lifespan. PLoS Genetics, 2014 Dec;10(12):e PMID: PMID: Leyton L, Hagood JS.Thy-1 modulates neurological cell-cell and cellmatrix interactions through multiple molecular interactions. Adv Neurobiol. 2014;8:3-20. Review. PMID: Manchenkov T, Pasillas MP, Haddad GG, Imam FB. Novel Genes Critical for Hypoxic Preconditioning in Zebrafish Are Regulators of Insulin and Glucose Metabolism. G3 (Bethesda) Apr 3;5(6): PMID: Udpa N*, Ronen R*, Zhou D*, Liang J, Stobdan T, Appenzeller O, Yin Y, Du Y, Guo L, Cao R, Wang Y, Jin X, Huang C, Jia W, Cao D, Guo G, Claydon VE, Hainsworth R, Gamboa JL, Zibenigus M, Zenebe G, Xue J, Liu S, Frazer KA, Li Y, Bafna V, Haddad GG. Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes. Genome Biol. 15(2):R36, (* equal contribution) PMID: Xie L, Ng C, Ali T, Valencia R, Ferreira BL, Xue V, Tanweer M, Zhou D, Haddad GG, Bourne PE, Xie L. Multiscale modeling of the causal functional roles of nssnps in a genome-wide association study: application to hypoxia. BMC Genomics. 14(Suppl 3):S9, Yang N, Garcia MA, Quinton PM. Normal mucus formation requires camp-dependent HCO3- secretion and Ca2+-mediated mucin exocytosis. J Physiol Sep 15;591(18): PMID: Pamenter ME, Haddad GG. High-throughput cell death assays. Methods Mol Biol. 2015; 1254: PMID: Quinton PM. A sysnopsis of methods of sweat tests in pathology. Clin Biochem. 2014; 47(9): PMID: Ronen R, Zhou D, Bafna V, Haddad GG. The genetic basis of chronic mountain sickness. Physiology (Bethesda). 29(6):403-12, Ross MK, Ellis LS, Bird LM, Hagood JS. Pulmonary interstitial glycogenosis in a patient ultimately diagnosed with Noonan syndrome. Pediatr Pulmonol May; 49(5): PMID: Sanders YY, Hagood JS, Liu H, Zhang W, Ambalavanan N, Thannickal VJ. Histone deacetylase inhibition promotes fibroblast apoptosis and ameliorates pulmonary fibrosis in mice. Eur Respir J 2014 May; 43(5): doi: / PMID: Scortegagna M, Kim H, Li JL, Yao H, Brill LM, Han J, Lau E, Bowtell D, Haddad GG, Kaufman RJ, Ronai ZA. Fine tuning of the UPR by the ubiquitin ligases Siah1/2. PLoS Genet May 8;10(5):e doi: /journal.pgen ecollection 2014 May. PMID: Shamsuddin AK and Quinton PM: Native Small Airways Secrete Bicarbonate. Am J Respir Cell Mol Biol. 50(4): PMID: Shepherd SL, Goodrich EJ, Desch J, Quinton PM. Counterpoint: does the risk of cross infection warrant exclusion of adults with cystic fibrosis from cystic fibrosis foundation events? No. Chest Apr; 145(4): PMID: Skalsky AJ, Lesser DJ, McDonald CM. Evaluation of phrenic nerve and diaphragm function with peripheral nerve stimulation and M-mode ultrasonography in potential pediatric phrenic nerve or diaphragm pacing candidates. Phys Med Rehabil Clin N Am Feb; 26(1): Smith KA1, Voiriot G, Tang H, Fraidenburg DR, Song S, Yamamura H, Yamamura A, Guo Q, Wan J, Pohl NM, Tauseef M, Bodmer R, Ocorr K, Thistlethwaite PA, Haddad GG, Powell FL, Makino A, Mehta D, Yuan JX. Notch Activation of Ca+ Signaling Mediates Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension. Am J Respir Cell Mol Biol Jan 8. PMID: Stobdan T, Zhou D, Ao-Ieong E, Ortiz D, Ronen R, Hartley I, Gan Z, McCulloch AD, Bafna V, Cabrales P, Haddad GG. Endothelin receptor B, a candidate gene from human studies at high altitude, improves cardiac tolerance to hypoxia in genetically engineered heterozygote mice. Proc Natl Acad Sci U S A. 112(33): , [Epub 2015 Aug 3]. Yin S, Xue J, Sun H, Wen B, Wang Q, Perkins G, Zhao HW, Ellisman MH, Hsiao YH, Yin L, Xie Y, Hou G, Zi J, Lin L, Haddad GG, Zhou D*, Liu S*. Quantitative Evaluation of the Mitochondrial Proteomes of Drosophila melanogaster Adapted to Extreme Oxygen Conditions. PLoS ONE 8(9):e74011, (*: co-correspondence) PMCID:PMC Zhao HW, Gu XQ, Chailangkarn T, Perkins G, Callacondo D, Appenzeller O, Poulsen O, Zhou D, Muotri AR, Haddad GG. Altered ipsc-derived neurons' sodium channel properties in subjects with Monge's disease. Neuroscience. 288:187-99, Zhou D, Udpa N, Ronen R, Stobdan T, Liang J, Appenzeller O, Zhao HW, Yin Y, Du Y, Guo L, Cao R, Wang Y, Jin X, Huang C, Jia W, Cao D, Guo G, Gamboa JL, Villafuerte F, Callacondo D, Xue J, Liu S, Frazer KA, Li Y, Bafna V, Haddad GG. Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness in Andean highlanders. Am J Hum Genet. 93(3):452-62, AWARDS & HONORS The Division was recognized among the top programs in Pediatric Pulmonology in the U.S. News & World Report in all years Marilynn Chan, MD Pediatric Scientist Development Program Award Paul Quinton, PhD 2015 Distinguished Achievement Award, American Thoracic Society 2014 Plenary Lecture, American Thoracic Society International Conference Best Doctors, Top Doctors: Gabriel Haddad, James Hagood, Daniel Lesser, Meerana Lim, Mark Pian, Julie Ryu 254 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 255

129 Vulnerable Children (The Chadwick Center) 256 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 257

130 258 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report INTRODUCTION The Chadwick Center for Children and Families is Rady Children s Hospital-San Diego (RCHSD) s response to child abuse and neglect, domestic violence, and post-traumatic stress in children. The staff is comprised of a variety of professionals in disciplines ranging from medicine and nursing to child development, social work, and psychology. The Chadwick Center ( is located off the main hospital campus at the Children s Hospital Health Services building and provides services at satellites from Oceanside to Chula Vista. Chadwick services are also delivered at the Polinsky Center and at a wide variety of community agencies. The Center works with overwhelmed families to prevent abuse and neglect, supports law enforcement and child protection services when abuse is suspected to accurately and sensitively gather the facts in ways that minimize secondary trauma, and then helps victimized children and their families heal through one of the largest specialized trauma mental health programs in the nation. The Chadwick Center s expertise in treating abuse-related trauma has led to collaborations with the National Child Traumatic Stress Network and the expansion of treatment to work with child and adolescent victims of other forms of violence (such as school shootings), natural disasters (wild fire victims), auto accidents and children undergoing painful medical procedures. DIVISION FAST FACTS The Center provides education to over 22,000 professionals from the US and 30 countries worldwide MAJOR PLANS AND GOALS The Chadwick Center should build upon its experience and reputation for quality and continue to expand the quality of service delivery, add new evidence-based practices, empirically test those practices, and then teach others locally, nationally, and internationally to deliver similar level quality services. The Chadwick Center should expand its leadership role locally and nationally in advocating for the best evidence-based or supported practice, teaching others to build their capacity, and assisting them to actually implement the practices in real world settings. The Chadwick Center should further build the engagement of its staff and focus on equipping its workforce with the knowledge, skills, tools, and resources they need to do extraordinary work. While RCHSD s Chadwick Center will never be able to serve all the children in need in San Diego, it should remain the safety net provider that brings the highest level of expertise to the most severely affected children and their families, while training others to deliver high quality services to less severely affected children Our program serves over 9,400 children and families annually Marilyn Kaufhold, MD Medical Director; Clinical Instructor Premi Suresh, MD Assistant Clinical Professor FACULTY The Chadwick Center serves over 9,400 children and families per year through two interrelated programs from three sites countywide. Forensic and Medical Services: Over 2,000+ children receive expert medical assessment or a forensic interview for abuse or are evaluated and treated for impaired growth and developmental concerns through the Failure to Thrive Clinic. Close to 1000 children are evaluated and treated medically at the Polinsky Children s Center. The Chadwick Center facilitates the weekly San Diego County Child Protection Team meeting to discuss complex child abuse cases marked the Team s 39th anniversary, making it one of the longest running multidisciplinary child abuse team meetings in the world. Attendees include hospital professionals, law enforcement, child protection professionals, and district attorneys. Trauma Counseling: 1,703 individual children and parents involved in child abuse, domestic violence and other forms The Chadwick Center has a long tradition of sponsoring nationally and internationally-recognized professional education opportunities. The Center provides professional education to more than 22,000 professionals from throughout the United States and 30 countries worldwide. In addition, the Center provided continuing medical education and support to several medical conferences to over 3,000 national pediatricians on advanced topics including cardiology, dermatology, genetics, neonatology, gastroenterology, neurology, infectious disease, adolescent medicine, and others. The Center supported the hospital s weekly Grand Rounds, which consists of various medical topics to over 15,000 physicians and healthcare staff. The Chadwick Center s Clinical Training Program provides training in the assessment and treatment of child abuse to professionals nationally and at the Center. The California Mandated Reporter Training web site ( is composed of seven modules and designed to train mandated child abuse reporters so they may carry out their responsibilities properly. To date, over 300,000 tests have been taken and the web site has been Wendy Wright, MD Staff Physician CLINICAL ACTIVITIES TEACHING ACTIVITIES Lorena Vivanco, MD Staff Physician of trauma attended more than 27,023 therapy sessions. The Chadwick Center continues to be among the leaders in the use of research supported therapies such as Trauma Focused Cognitive Behavioral Therapy (TF-CBT), Parent-Child Interaction Therapy (PCIT) and Child Parent Psychotherapy (CPP) for very young trauma victims. Additionally many children and caretakers are emotionally prepared to testify in court through the Kids & Teens in Court program, helping reduce their fear and anxiety of testifying in front of the person who hurt them. San Diego County continues to utilize the services of Rady Children s to design and manage the KidSTART system for San Diego focusing on very young children with severe emotional and developmental challenges, often associated with extreme trauma exposure. This is a joint project of the Chadwick Center, Developmental Services and Psychiatry with Chadwick leading the young child mental health treatment component. In KidSTART, more than 405 individual children were seen and attended many therapy sessions. visited by over 400,000 individuals. For more than two decades, the Chadwick Center at Rady Children s has led the world in developing strategies and programs to prevent child abuse through the San Diego International Conference on Child Maltreatment, hosted by the Chadwick Center. This past January, the Chadwick Center held its 30 th Annual Conference, drawing more than 2,000 attendees from the United States and around the world. Each year, this conference seeks to provide research evidencebased best practices to professionals working in the fields of medicine, mental health, criminal justice, child welfare, public policy and research. The conference includes more than 150 workshops and world-renowned speakers. And because each year in the United States, approximately five million children experience some form of traumatic experience, the Center s impact is more important than ever. The Chadwick Center also continues to be a national and state leader in the identification and spread of research-based clinical practices. This work includes a heavy demand for Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 259

131 Chadwick Center speakers around the nation. Rady Children s Chadwick Center expanded its California Evidence Based Clearinghouse for Child Welfare which is charged with helping reform the state s child welfare services using researchsupported practice models. This web based resource, which now includes 42 topic areas with reviews on over 339 separate program models and 20 screening and assessment tools (www. cebc4cw.org), has been visited by over 640,455 individuals from 219 countries/territories. Some of the topics included RESEARCH SUPPORT CEBC16(PI) January 1, 2004 June 30, 2016 $4,821,930 CA Department of Social Services, Office of Child Abuse and Neglect California Evidence-Based Clearinghouse (CEBC)" 5U79SM061266(PI) Sep 30, 2011 Sep 29, 2016 $2,300,000 US Department of Health and Human Services, Substance Abuse and Mental Health Services Administration Chadwick Trauma-Informed Systems Dissemination and Implementation Project (CTISP-DI) 90C01101 (PI) Sept 30, 2012 Sept 29, 2017 $3,200,000 US Department of Health and Human Services, Administration for Children and Families California Screening, Assessment, and Treatment Initiative (CASAT) PUBLICATIONS Kisiel, C., Conradi, L., Fehrenbach, T., Torgerson, E., & Briggs, E.C.(2014). Assessing the effects of trauma in children and adolescents in practice settings. Journal of Child and Adolescent Psychiatric Clinics of North America, 23, Conradi, L., Landsverk, J., & Wotring, J. (2014). Screening, assessing, monitoring outcomes and using evidence-based interventions to improve the well-being of children in child welfare. Integrating Safety, Permanency and Well-Being Series. Washington D.C.: Department of Health and Human Services, Children s Bureau Retrieved December 22, 2014 from edu/resources/wp2%20%20screening%20assesing%20and%2 Monitoring%20508%20v2.pdf Conradi, L., & Kisiel, C. (2013). Trauma screening within the child welfare system. CW360: Trauma-Informed Child Welfare Practice, Winter, 21. Williams, K. N. & Crandal, B. R. (2015). Modular CBT for Children and Adolescents with Depression: A Clinician s Guide to Individualized Treatment. Oakland, CA: New Harbinger Publications. Crandal, B. R., Foster, S. L., Chapman, J. E., Cunningham, P. B., Brennan, P. A., Whitmore, E. A. (2015). Therapist Perception of Treatment Outcome: Evaluating treatment outcomes among youth with antisocial behavior problems. Psychological Assessment, 27, pp Horwitz, S. M., Hurlburt, M. S., Heneghan, A., Zhang, J., Rolls- RESEARCH ACTIVITIES on the website include Cultural resources, General Tools and resources for the professional to utilize in their practice. In addition to these professional education programs, the Chadwick Center provides education to pediatric residents form UCSD, Naval Medical Center, San Diego, and other states and emergency department fellows through core rotations during the training years. Reutz, J., Landsverk, J., & K Stein, R. E. (2013). Persistence of Mental Health Problems in Very Young Children Investigated by US Child Welfare Agencies. Academic Pediatrics, 13(6), Stein, R. E., Hurlburt, M. S., Heneghan, A. M., Zhang, J., Rolls- Reutz, J., Silver, E. J.,... & Horwitz, S. M. (2013). Chronic Conditions Among Children Investigated by Child Welfare: A National Sample. Pediatrics, 131(3), Acri, M. C., Palinkas, L., Hoagwood, K. E., Shen, S., Schoonover, D., Reutz, J. R., & Landsverk, J. (2014). Interorganizational Relationships Among Family Support Organizations and Child Mental Health Agencies. Administration and Policy in Mental Health and Mental Health Services Research, 41(4), Fowler, P. J., Motley, D., Zhang, J., Rolls-Reutz, J., & Landsverk, J. (2014). Adolescent maltreatment in the child welfare system and developmental patterns of sexual risk behaviors. Child maltreatment, Holmes, L., Landsverk, J., Ward, H., Rolls-Reutz, J., Saldana, L., Wulczyn, F., & Chamberlain, P. (2014). Cost calculator methods for estimating casework time in child welfare services: A promising approach for use in implementation of evidence-based practices and other service innovations. Children and Youth Services Review, 39, Horwitz, S. M., Hurlburt, M. S., Goldhaber-Fiebert, J. D., Palinkas, L. A., Rolls-Reutz, J., Zhang, J.,... & Landsverk, J. (2014). Exploration and adoption of evidence-based practice by US child welfare agencies. Children and Youth Services Review, 39, Stein, R. E., Hurlburt, M. S., Heneghan, A. M., Zhang, J., Rolls- Reutz, J., Landsverk, J., & Horwitz, S. M. (2014). Health Status and Type of Out-of-Home Placement: Informal Kinship Care in an Investigated Sample. Academic pediatrics, 14(6), Heneghan, A., Stein, R. E., Hurlburt, M. S., Zhang, J., Rolls-Reutz, J., Kerker, B. D.,... & Horwitz, S. M. (2015). Health-Risk Behaviors in Teens Investigated by US Child Welfare Agencies. Journal of Adolescent Health, 56(5), Walsh, C., Rolls Reutz, J., & Williams, R. (2015). Selecting and implementing evidence-based practices: A guide for child and family serving systems. San Diego, CA: California Evidence-Based Clearinghouse for Child Welfare. Walsh, C. (November/December 2014) An educational resource for evidence-based practice. Social Work Today, 14(6), Walsh, C. (November/December 2014) An educational resource for evidencebased practice. Social Work Today, 14(6), Berliner, L., Fitzgerald, M., Dorsey, S., Chaffin, M., Ondersma, S., Wilson, C. (2015): Report of the APSAC Task Force on Evidence- Based Service Planning Guidelines for Child Welfare. Child Maltreatment, Vol. 20, No 1, February, 2015 Sage. AWARDS & HONORS NCA Recertification - The Board of the National Children s Alliance, the national accrediting body for multi-disciplinary child abuse centers awarded the Chadwick Center full accreditation status for the next five years after thorough review and site visit. Lorena Vivanco, MD, Top Doctors 2014 "Physicians of Exceptional Excellence" in San Diego Magazine. Marilyn Kaufhold, MD, received the Physician Excellence Award for Excellence in Clinical Care Al Killen-Harvey, LCSW, currently serves as the co-chair of the Cultural Consortium for the National Child Traumatic Stress Network. Charles Wilson selected 2015 Social Worker of the Year: Helping Families Flourish Award Macro Category by the schools of Social Work at USC, SDSU, CSUSM and the San Diego Chapter of the National Association of Social Workers. Jennifer Hossler Co-Chair of the NCTSN Child Welfare Trauma Training Toolkit (CWTTT) Subcommittee, presented throughout this time on the Child Wwelfare Trauma Training Toolkit across the United States. Presented on trauma-informed systems in Minnesota. 260 UC SAN DIEGO DEPARTMENT OF PEDIATRICS Biennial Report Biennial Report UC SAN DIEGO DEPARTMENT OF PEDIATRICS 261

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