Endophenotypes of food allergy in response to oral immunotherapy

项目总结 候选人：Yamini Virkud，医学博士，MA，公共卫生硕士，目标是成为一名由NIH资助的独立内科科学家和 食物过敏综合系统基因组学领域的领先专家。为了实现这一目标，她一直在 从事食物过敏免疫治疗临床研究5年，获硕士学位 生物医学科学和生物统计学公共卫生硕士学位，并一直与世界- 食物过敏研究领域的知名领导者。她现在是儿科过敏症专科医生和免疫学家 麻省总医院，哈佛医学院儿科讲师，副 布里格姆妇女医院的流行病学家。她的目标是成为一名独立调查员，通过 追求以下目标：(1)培训RICH组学的临床试验和综合网络分析 数据集，(2)发表她的发现并扩大她的合作者网络，(3)建立一个社区 同时也是成功导师的专家，(4)完善她的统计和计算课程 教育背景。这将为她的第一个R01应用程序做好准备，并允许她开发自己的应用程序 食物过敏集成系统生物学的独特利基。 研究：在过去的十年里，儿童食物过敏的患病率一直在增加，而且 食物过敏的管理仅限于避免过敏原。口服免疫疗法(OIT)，摄取 逐渐增加过敏原的数量以防止意外接触，这是一项调查 干预现在有望成为首批被批准的食物过敏疗法之一。然而，个人 对治疗的反应以我们不了解的方式变化，临床使用的耐受性主要是 受限于严重的过敏不良事件。这项提案详细说明了一项五年计划，为维库德博士提供 培训以评估OIT的安全性和治疗结果之间的相互作用，这些因素如何定义严重的 食物过敏的内表型，内表型背后的免疫机制。她提出了一项 创新和强大的设计，通过结合临床和免疫学来实现这些目标 测量、转录组和代谢组学数据集。这项研究旨在指导……的发展 一种新的免疫疗法或辅助疗法的发现，以提高OIT的安全性和有效性。 环境：维尔库德博士将在两个世界知名的机构进行这项研究。她设计了一种 食物过敏治疗和免疫耐受领域的领军人物韦恩·施雷夫勒博士之间的双重指导 马萨诸塞州总医院的研究人员和基因组学专家Jessica Lasky-Su博士 布里格姆妇女医院网络医学钱宁分部哮喘的代谢组学研究。她 还召集了一个由遗传流行病学专家组成的咨询委员会，其中包括斯科特·韦斯博士， 本杰明·拉比和大卫·克里斯汀尼。这一指导和咨询团队的组合，以及 哈佛大学的许多资源，将确保她成功地过渡到独立。

PROJECT SUMMARY Candidate: Yamini Virkud, MD, MA, MPH, aims to become an independent NIH-funded physician-scientist and leading expert in the field of integrated systems genomics of food allergy. To achieve this goal, she has been conducting clinical research in food allergy immunotherapy outcomes for the past 5 years, obtained a masters in biomedical sciences and a masters of public health in biostatistics, and has been working with world- renowned leaders in food allergy research. She is now a pediatric allergist and immunologist at Massachusetts General Hospital, an Instructor in Pediatrics at Harvard Medical School, and Associate Epidemiologist at Brigham & Women’s Hospital. She aims to build a career as an independent investigator by pursuing the following goals: (1) training in clinical trials and integrated network analyses of rich –omics datasets, (2) publishing her findings and expanding her network of collaborators, (3) establishing a community of experts who are also successful mentors, (4) coursework to round out her statistical and computational educational background. This will prepare her for her first R01 application and allow her to develop her own distinct niche of integrated systems biology of food allergy. Research: The prevalence of pediatric food allergy has been increasing over the last decade, and management of food allergies is limited to avoidance of the allergen. Oral immunotherapy (OIT), the ingestion of gradually increasing amounts of allergen to protect against accidental exposure, is an investigational intervention now poised to become one of the first approved therapies for food allergy. However, individual responses to therapy vary in ways that we do not understand, and its tolerability for clinical use is primarily limited by significant allergic adverse events. This proposal details a five-year plan to provide Dr. Virkud with training to evaluate the interaction between safety and therapeutic outcomes of OIT, how these define a severe endophenotype of food allergy, the immune mechanisms underlying endophenotypes. She has proposed an innovative and strong design to address these objectives using a combination of clinical and immunologic measures, transcriptomics and metabolomics datasets. This research is intended to guide the development of a novel immunotherapy or the discovery of adjunctive therapies to improve the safety and efficacy of OIT. Environment: Dr. Virkud will conduct this research at two world-renowned institutions. She has designed a dual mentorship between Dr. Wayne Shreffler, a leader in food allergy therapeutics and immune tolerance research at Massachusetts General Hospital, and Dr. Jessica Lasky-Su, an expert in genomics and metabolomics of asthma at the Channing Division of Network Medicine, Brigham & Women’s Hospital. She has also gathered an advisory committee of experts in genetic epidemiology, including Drs. Scott Weiss, Benjamin Raby, and David Christiani. The combination of this mentorship and advisory team, along with the many resources of Harvard University, will ensure her success in transitioning towards independence.