Systems approach to elucidate the microbiome's influence on the development of food allergies early in life

项目总结 候选人：维多利亚·M·马丁，医学博士，公共卫生硕士，目标是成为美国国立卫生研究院资助的独立内科科学家和 在黏膜食物过敏疾病方面的系统免疫学方面的公认专家。为了实现这一目标，她有 建立了一个大型前瞻性观察队列，旨在回答该奖项下提出的问题，同时 通过流行病学和培训获得临床有效性公共卫生硕士学位 生物统计学。她是一名儿科胃肠病专家，也是美国儿科胃肠病科的联席主任 马萨诸塞州综合医院食物过敏中心，哈佛大学儿科学讲师 医学院。她有雄厚的研究基础，但需要在三个关键方面接受大量高级培训 领域：(1)综合纵向微生物组分析，(2)系统免疫学和高级 计算建模，以及(3)临床研究方法和领导力发展。她所受的训练 根据该奖项提出的目标和研究旨在为她的第一次R01申请做准备，并将 允许她在胃肠道食物过敏的集成系统生物学领域开拓自己独特的利基市场。 研究：食物过敏是一种潜在威胁生命的疾病，其在儿童中的患病率不断上升 生物学上的解释尚不清楚，但微生物群和粘膜免疫系统的作用是 正在接受调查。食物蛋白诱导的过敏性直肠炎(FPIAP)通常是最早和最常见的 食物过敏的表现，但对其病理生理或与其他食物的关系知之甚少 过敏性疾病，使其成为前瞻性研究的重要模型。这项提案概述了一个五年计划 使用马丁博士精心设计的大型观察队列来调查假说的研究计划 (1)患有新生儿肺炎的婴儿肠道菌群失调在发病前受到以下因素的影响 饮食，并驱动肠道炎症的途径；以及(2)FPIAP是特应性进行曲和 潜在的FPIAP病理生理学和饮食回避共同增加了IgE-FA的风险。这项提议旨在 阐明食物过敏最早表现的潜在机制，验证新的生物标记物 研究食物过敏的发展，并为初级食物过敏预防确定重要的新目标。 环境：根据决斗，马丁博士将在马萨诸塞州综合医院进行这项研究 儿童食物过敏和免疫耐受领域的思想领袖韦恩·施雷夫勒医生的指导 阿莱西奥·法萨诺博士，他是微生物群和胃肠生理学方面的世界知名专家。 她组建了一个由粘膜免疫学专家组成的培训咨询委员会(W.Allan Walker，医学博士)， 食物过敏流行病学(Corinne Keet，MD，MS，PhD)，系统免疫学(Jessica Lasky-Su，ScD)，以及 计算微生物组分析(Vanni Bucci，博士；Moran Yassour，博士)。这两者的结合 哈佛大学出众的导师和顾问团队以及丰富的资源将确保她 在一个与她的每一位导师截然不同的领域成功过渡到独立。

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 combination of this exceptional mentorship and advisory team and expansive resources at Harvard University will ensure her success in transitioning to independence in an area distinct from each of her mentors.