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

阐明微生物组对生命早期食物过敏发展的影响的系统方法

• 批准号: 10318652
• 负责人: Victoria Mackenzie Martin
• 金额: $ 19.96万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-14 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10318652
• 关键词: 16S ribosomal RNA sequencing; Acids; Advisory Committees; Age; Age-Years; Allergic; Allergic Disease; Allergic inflammation; Antibiotics; Antigens; Area; Atopic Dermatitis; Award; Biological; Biological Markers; Biometry; Child; Childhood; Clinical; Clinical Research; Clinical Sciences; Clinical effectiveness; Cohort Studies; Colonic inflammation; Complex; Computer Models; Data; Development; Diagnosis; Diet; Disease; Doctor of Philosophy; Enrollment; Ensure; Enterobacteriaceae; Environment; Environmental Risk Factor; Eosinophil-Derived Neurotoxin; Epidemiology; Food; Food Hypersensitivity; Foundations; Functional disorder; Funding; Gastroenterologist; Gastroenterology; Gastrointestinal Physiology; Gastrointestinal tract structure; General Hospitals; Goals; Hypersensitivity; IgE; Immune Tolerance; Immune response; Immunology; Incidence; Infant; Inflammatory; Innate Immune System; Leukocyte L1 Antigen Complex; Life; Longitudinal Studies; Massachusetts; Master of Public Health; Mediating; Mentors; Mentorship; Metadata; Modeling; Mucosal Immune System; Mucous Membrane; Onset of illness; Outcome; Pathway interactions; Pediatrics; Pharmaceutical Preparations; Phenotype; Physicians; Positioning Attribute; Prevalence; Prevention; Proctocolitis; Prospective Studies; Proteins; Research; Research Design; Research Personnel; Resources; Risk; Role; Sampling; Scientist; Shotguns; Symptoms; System; Systems Biology; Testing; Training; United States; United States National Institutes of Health; Universities; Walkers; Work; atopy; base; candidate marker; cohort; design; dietary; dysbiosis; eosinophil; experience; food antigen; gastrointestinal; gut inflammation; gut microbiome; infancy; insight; instructor; leadership development; medical schools; metagenomic sequencing; method development; microbial; microbiome; microbiome analysis; novel; novel marker; post-doctoral training; prospective; success

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.

项目摘要 候选人：维多利亚M。马丁，医学博士，公共卫生硕士的目标是成为一个独立的美国国立卫生研究院资助的医生科学家， 粘膜食物过敏性疾病系统免疫学方面的公认专家。为了实现这一目标，她 建立了一个大型的前瞻性观察队列，旨在回答该奖项提出的问题， 通过流行病学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学家，也是儿科胃肠病科的联合主任。 马萨诸塞州总医院的食物过敏中心和哈佛的儿科讲师 医学院她有很强的研究基础，但需要在三个关键领域进行大量的高级培训。 领域：（1）综合纵向微生物组分析，（2）系统免疫学与高级 计算建模，（3）临床研究方法和领导力发展。她的训练 该奖项的目标和研究旨在为她的第一个R 01申请做好准备，并将 使她能够在胃肠道食物过敏的综合系统生物学方面发展自己独特的利基。 研究：食物过敏是一种潜在的危及生命的疾病，在儿童中的患病率越来越高， 生物学解释仍不清楚，但微生物组和粘膜免疫系统的作用是 正在调查食物蛋白诱导的过敏性直肠结肠炎（FPIAP）通常是最早和最常见的 食物过敏是食物过敏的一种表现，但对其病理生理学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。这份提案概述了一项为期五年的 一项研究计划，使用马丁博士精心设计的大型观察队列来调查假设 （1）FPIAP婴儿的肠道微生物组在疾病发作前存在生态失调， 饮食，并驱动肠道炎症的途径;和（2）FPIAP是特应性行军的第一步， 潜在的FPIAP病理生理学和饮食回避共同增加了IgE-FA的风险。这项建议旨在 阐明食物过敏最早期表现的潜在机制，验证新的生物标志物 食物过敏的发展，并确定重要的新目标，初级食物过敏预防。 环境：马丁博士将在马萨诸塞州总医院进行这项研究， 韦恩Shreffler博士的指导，在儿科食物过敏和免疫耐受领域的思想领袖 Alessio法萨诺博士是世界知名的微生物组和胃肠道生理学专家。 她组建了一个粘膜免疫学专家培训咨询委员会（W。Allan步行者，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，PhD; Moran Yassour，PhD）。这两者的结合 哈佛大学卓越的指导和咨询团队以及丰富的资源将确保她 成功地过渡到独立的领域不同于她的每一个导师。