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: 10531599
• 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/10531599
• 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 Diseases; 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; Work; atopy; biomarker validation; candidate identification; 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; research and development; 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：MPH的维多利亚·马丁（Victoria M. 公认的粘膜食物过敏性疾病系统免疫学专家。为了实现这一目标，她有 建立了一个庞大的前瞻性观察队列，旨在回答该奖项下提出的问题，而 通过流行病学培训和 生物统计学。她是小儿胃肠病学家，也是小儿胃肠病学部分的联合指导者 马萨诸塞州综合医院的食物过敏中心和哈佛的儿科讲师 医学院。她拥有强大的研究基础，但需要在三个钥匙中进行大量高级培训 区域：（1）综合纵向微生物组分析，（2）具有先进的系统免疫学 计算建模以及（3）临床研究方法和领导力发展。她的训练 根据该奖项提出的目标和研究旨在为她的第一个R01申请做好准备，并将 让她在胃肠道食物过敏的综合系统生物学中发展自己独特的利基市场。 研究：食物过敏是一种潜在的威胁生命的疾病，儿童患病率的增加 生物学解释尚不清楚，但是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前结肠炎（FPIAP）通常是最早，最常见的 食物过敏的表现，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。该提案概述了五年 研究计划使用Martin博士精心设计的大型观察队列研究来研究这些假设 （1）FPIAP婴儿肠道微生物组的营养不良，先于疾病发作，受到疾病发作的影响 饮食，并驱动肠炎的途径； （2）FPIAP是Atopic March和 基本的FPIAP病理生理学和饮食避免共同增加了IGE-FA的风险。该提议的目的 为了阐明食物过敏最早表现的潜在机制，验证了新型生物标志物 食物过敏的发展，并确定预防原发性食物过敏的重要新目标。 环境：马丁博士将在马萨诸塞州综合医院进行这项研究 韦恩·什里夫勒（Wayne Shreffler）博士的指导，小儿食物过敏和免疫耐受性的思想领袖 研究，以及微生物组和胃肠道生理学的世界知名专家Alessio Fasano博士。 她已经组建了粘膜免疫学专家培训咨询委员会（W. Allan Walker，马里兰州）， 食品过敏流行病学（Corinne Keet，医学博士，MS，PhD），系统免疫学（Jessica Lasky-SU，SCD）和 计算微生物组分析（Vanni Bucci，博士； Moran Yassour，PhD）。这个结合 哈佛大学的卓越指导和咨询团队以及广泛的资源将确保她 在与每个导师不同的领域过渡到独立的成功。