Endophenotypes of food allergy in response to oral immunotherapy

项目摘要 候选人：Yamini Virkud，MD，MA，MPH，旨在成为一名独立的NIH资助的医生科学家， 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， 在过去5年进行食物过敏免疫治疗结果的临床研究，获得硕士学位 在生物医学科学和生物统计学公共卫生硕士，并一直与世界- 食物过敏研究领域的知名领导者她现在是一名儿科过敏症和免疫学家， 马萨诸塞州总医院，哈佛医学院儿科讲师， 布莱根妇女医院的流行病学家她的目标是建立一个职业生涯作为一个独立的调查员， 追求以下目标：（1）丰富组学的临床试验和集成网络分析培训 数据集，（2）发布她的发现并扩大她的合作者网络，（3）建立社区 专家谁也是成功的导师，（4）课程，以完善她的统计和计算 教育背景。这将为她的第一个R 01应用程序做好准备，并允许她开发自己的 食物过敏综合系统生物学的独特生态位。 研究：在过去的十年里，儿童食物过敏的患病率一直在增加， 食物过敏的处理仅限于避免过敏原。口服免疫疗法（OIT）， 逐渐增加过敏原的数量，以防止意外暴露，是一项研究 现在，这种干预有望成为首批批准的食物过敏疗法之一。但个别 对治疗的反应以我们不了解的方式变化，其临床使用的耐受性主要是 受严重过敏性不良事件的限制。该提案详细说明了一项五年计划，为Virkud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，这些如何定义严重的 食物过敏的内在表型，内在表型的免疫机制。她提出了一个 创新和强大的设计，以解决这些目标，使用临床和免疫学的组合， 测量、转录组学和代谢组学数据集。本研究旨在指导 一种新的免疫疗法或发现预防性疗法，以提高OIT的安全性和有效性。 环境：Virkud博士将在两个世界知名的机构进行这项研究。她设计了一个 韦恩什里夫勒博士，在食物过敏治疗和免疫耐受的领导者之间的双重导师 研究在马萨诸塞州总医院，和杰西卡博士Lasky-Su，在基因组学和 在布里格姆妇女医院网络医学Channing分部进行的哮喘代谢组学研究。她 还召集了一个遗传流行病学专家咨询委员会，包括斯科特韦斯博士， 本杰明·拉比和大卫·克里斯蒂安尼。这种指导和咨询团队的结合，沿着 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.