PROJECT SUMMARY Candidate: Victoria M. Martin, MD, MPH aims to become an independent NIH-funded physician scientist and recognized expert in systems immunology in mucosal food allergic diseases. To achieve this goal, she has built a large prospective observational cohort designed to answer the questions posed under this award, while obtaining a Master of Public Health degree in Clinical Effectiveness with training in epidemiology and biostatistics. She is a pediatric gastroenterologist and Co-Director of the Pediatric Gastroenterology Section of the Food Allergy Center at the Massachusetts General Hospital, and an Instructor in Pediatrics at Harvard Medical School. She has a strong research foundation but requires substantial advanced training in three key areas: (1) Integrated Longitudinal Microbiome Analyses, (2) System Immunology with Advanced Computational Modeling, and (3) Clinical Research Methods and Leadership Development. Her training objectives and research posed under this award are aimed to prepare her for her first R01 application and will allow her to develop her own distinct niche in integrated systems biology of gastrointestinal food allergy. Research: Food allergy is a potentially life-threatening disease with increasing prevalence in children for which the biological explanation remains unclear, but the role of the microbiome and mucosal immune system are being investigated. Food protein-induced allergic proctocolitis (FPIAP) is often the earliest and most common manifestation of food allergy and yet little is known about its pathophysiology or its relationship to other food allergic diseases, making it an important model for prospective study. This proposal outlines a five-year research plan using a large observational cohort carefully designed by Dr. Martin to investigate the hypotheses that (1) a dysbiosis in the intestinal microbiome of infants with FPIAP precedes disease onset, is influenced by diet, and drives pathways of intestinal inflammation; and (2) FPIAP is a first step on the atopic march and the underlying FPIAP pathophysiology and dietary avoidance together increase risk for IgE-FA. This proposal aims to elucidate underlying mechanisms for the earliest manifestations of food allergies, validate novel biomarkers of food allergy development, and identify important novel targets for primary food allergy prevention. Environment: Dr. Martin will conduct this research at Massachusetts General Hospital, under the duel mentorship of Dr. Wayne Shreffler, a thought leader in the field of pediatric food allergy and immune tolerance research, and Dr. Alessio Fasano, a world-renowned expert in the microbiome and gastrointestinal physiology. She has assembled a training advisory committee of experts in mucosal immunology (W. Allan Walker, MD), food allergy epidemiology (Corinne Keet, MD, MS, PhD), systems immunology (Jessica Lasky-Su, ScD), and computational microbiome analysis (Vanni Bucci, PhD; Moran Yassour, PhD). The combin...