Function of RELMβ in oral tolerance breakdown in food allergy

项目摘要/摘要： 研究：食物过敏是一种潜在威胁生命的健康状况，影响到越来越多的 仅在美国就有个人。目前对食物过敏患者的日常管理受到 无法获得可靠的生物标记物来准确预测疾病的发病、严重程度和消退，以及 缺乏根治疗法来替代，严格避免罪魁祸首的饮食。更深入地了解其他 除了免疫球蛋白E以外，作用于食物过敏发病机制的机制将是填补这些空白的关键。这项建议 详细说明了一项五年计划，为克雷斯塔尼博士提供培训和专业知识，以评估RELMb作为 一种新的生物标志物和分子参与者在食物过敏中的建立和扩展 在食物过敏的小鼠模型和食物过敏儿童中的观察。综合评价 RELMb在食物过敏中的作用的研究有望识别疾病急需的生物标记物(S) 和可能的治疗干预目标，这将是未来纵向调查和 可能会显著影响食物过敏患者的日常护理和生活质量。 候选人：克雷斯塔尼博士的长期目标是成为一名独立的、由NIH资助的研究人员，专注于 食物过敏的疾病机制和生物标记物，目的是改善目前不太理想的食物过敏治疗 对食物过敏的人。对新的生物标志物和治疗方法的迫切需求和未得到满足的需求 在食物过敏方面。为了实现这一目标，她的短期目标是获得生物统计学、数据方面的进一步培训 分析、实验室技术，以及队列建设和管理方面的实用技能。这将是 完成正式课程，协作工作，出席会议，并从建立的指导 具有相关专业知识的导师/科学顾问。这将产生一个独特的实践技能和 科学知识，将成功地定位她的R01申请和独立的职业生涯作为 内科医生--食物过敏领域的科学家。 环境：克雷斯塔尼博士将由Chatila博士(主要导师)指导，他是 食物过敏机制和NIH全额资助实验室的负责人，以及Phipatanakul博士(共同导师)， 在哮喘和过敏性疾病方面的流行病学、人类队列和临床研究方面的专家。克雷斯塔尼博士 组建了一支非凡的顾问团队，包括Lynda Schneider博士、Kari Nadeau博士和Rima博士 Kaddurah-Daouk，他们投入了时间、资源和专业知识来促进克雷斯塔尼博士的职业生涯 开发并成功完成拟议的项目。在此颁奖期间，克雷斯塔尼博士将 通过哈佛大学公共卫生学院(HSPH)获得临床有效性公共卫生硕士学位， 并完成额外的补充课程作业。导师们营造的学术环境， 机构和整个哈佛社区将为学习和研究的实施提供理想的环境 这将保证克雷斯塔尼博士转变为一名非常成功的独立调查员。

PROJECT SUMMARY/ABSTRACT: Research: Food allergy is a potentially life-threatening health condition that affects an increasing proportion of individuals in the US alone. Current daily management of patients with food allergies is limited by the unavailability of reliable biomarkers to accurately predict onset, severity and resolution of disease, and by the lack of curative treatments to replace strict avoidance of the culprit food. A deeper understanding of additional mechanisms - other than IgE - acting in food allergy pathogenesis will be key in filling these gaps. This proposal details a five-year plan to provide Dr. Crestani with the training and expertise to evaluate the role of RELMb as a novel biomarker and molecular player in food allergy building and expanding on strong preliminary observations both in a murine model of food allergy and in food allergic children. The comprehensive evaluation of the role of RELMb in food allergy holds the promise of identifying strongly needed biomarker(s) of disease and possible targets for therapeutic interventions which will be the focus of future longitudinal investigations and may significantly impact the daily care and quality of life of food allergic patients. Candidate: Dr. Crestani long-term goal is to become an independent, NIH-funded investigator focused on disease mechanisms and biomarkers of food allergy, with the goal of improving the currently suboptimal care of food-allergic individuals. There is an urgent and unmet need for novel biomarkers and therapeutic approaches in food allergies. To achieve this goal, her short-term objectives are to obtain further training in biostatistics, data analysis, laboratory techniques, as well as practical skills in cohort building and management. This will be accomplished with formal classes, collaborative work, attendance at conferences, and guidance from established mentors/scientific advisors with relevant expertise. This will result in a unique combination of practical skills and scientific knowledge that will successfully position her for an R01 application and an independent career as a physician-scientist in the field of food allergy. Environment: Dr. Crestani will be mentored by Dr. Chatila (Primary Mentor), a leader investigator in mechanisms of food allergy and head of a fully NIH-funded laboratory, and Dr. Phipatanakul (Co-Mentor), an expert in epidemiology, human cohorts, and clinical investigation in asthma and allergic diseases. Dr. Crestani has assembled an extraordinary team of advisors, including Drs. Lynda Schneider, Kari Nadeau and Rima Kaddurah-Daouk, who have committed their time, resources, and expertise to facilitate Dr. Crestani’s career development and successful completion of the proposed project. During this award period, Dr. Crestani will obtain a Master of Public Health in Clinical Effectiveness through the Harvard School of Public Health (HSPH), and complete additional complementary coursework. The academic environment created by the mentors, institution, and Harvard community at large will provide the ideal milieu for learning and research implementation that will guarantee Dr. Crestani transition into a highly successful independent investigator.