Function of RELMβ in oral tolerance breakdown in food allergy

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PROJECT SUMMARY/ABSTRACT: Research: Food allergy is a potentially life-threatening health condition that affects an increasing proportion of individuals in the US alone. Current daily management of patients with food allergies is limited by the unavailability of reliable biomarkers to accurately predict onset, severity and resolution of disease, and by the lack of curative treatments to replace strict avoidance of the culprit food. A deeper understanding of additional mechanisms - other than IgE - acting in food allergy pathogenesis will be key in filling these gaps. This proposal details a five-year plan to provide Dr. Crestani with the training and expertise to evaluate the role of RELMb as a novel biomarker and molecular player in food allergy building and expanding on strong preliminary observations both in a murine model of food allergy and in food allergic children. The comprehensive evaluation of the role of RELMb in food allergy holds the promise of identifying strongly needed biomarker(s) of disease and possible targets for therapeutic interventions which will be the focus of future longitudinal investigations and may significantly impact the daily care and quality of life of food allergic patients. Candidate: Dr. Crestani long-term goal is to become an independent, NIH-funded investigator focused on disease mechanisms and biomarkers of food allergy, with the goal of improving the currently suboptimal care of food-allergic individuals. There is an urgent and unmet need for novel biomarkers and therapeutic approaches in food allergies. To achieve this goal, her short-term objectives are to obtain further training in biostatistics, data analysis, laboratory techniques, as well as practical skills in cohort building and management. This will be accomplished with formal classes, collaborative work, attendance at conferences, and guidance from established mentors/scientific advisors with relevant expertise. This will result in a unique combination of practical skills and scientific knowledge that will successfully position her for an R01 application and an independent career as a physician-scientist in the field of food allergy. Environment: Dr. Crestani will be mentored by Dr. Chatila (Primary Mentor), a leader investigator in mechanisms of food allergy and head of a fully NIH-funded laboratory, and Dr. Phipatanakul (Co-Mentor), an expert in epidemiology, human cohorts, and clinical investigation in asthma and allergic diseases. Dr. Crestani has assembled an extraordinary team of advisors, including Drs. Lynda Schneider, Kari Nadeau and Rima Kaddurah-Daouk, who have committed their time, resources, and expertise to facilitate Dr. Crestani’s career development and successful completion of the proposed project. During this award period, Dr. Crestani will obtain a Master of Public Health in Clinical Effectiveness through the Harvard School of Public Health (HSPH), and complete additional complementary coursework. The academic environment created by the mentors, institution, and Harvard community at large will provide the ideal milieu for learning and research implementation that will guarantee Dr. Crestani transition into a highly successful independent investigator.