Function of RELMβ in oral tolerance breakdown in food allergy

RELMβ 在食物过敏口服耐受破坏中的作用

• 批准号: 10301157
• 负责人: Elena Crestani
• 金额: $ 19.49万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-09 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10301157
• 关键词: Address; Affect; Age; Allergens; Allergic; Allergic Disease; Anaphylaxis; Asthma; Atopic Dermatitis; Award; Biological Markers; Biometry; Caring; Cells; Child; Childhood; Clinical; Clinical effectiveness; Communities; Data Analyses; Development; Diagnosis; Disease; Disease Outcome; Environment; Environmental Risk Factor; Epidemic; Epidemiology; Equilibrium; Evaluation; Five-Year Plans; Food; Food Hypersensitivity; Foundations; Frequencies; Funding; Future; GATA3 gene; Generations; Genetic; Goals; Head; Health; Human; IgE; Immune; Impairment; Individual; Institution; Interleukin-4; Investigation; Knowledge; Laboratories; Learning; Life; Life Style; Master of Public Health; Mediating; Mentors; Modernization; Molecular; Mucous Membrane; Mus; Pathogenesis; Pathogenicity; Patients; Physicians; Plasma; Play; Positioning Attribute; Prevalence; Production; Public Health; Public Health Schools; Quality of life; Regulation; Regulatory T-Lymphocyte; Research; Research Personnel; Resolution; Resources; Risk; Role; Scientist; Serum; Severities; Signal Transduction; Techniques; Testing; Therapeutic Intervention; Time; Training; Translations; United States National Institutes of Health; Work; allergic response; base; biomarker development; biomarker discovery; candidate marker; career; career development; clinical application; clinical investigation; cohort; curative treatments; enteric pathogen; food protection; gut microbiome; improved; mast cell; metabolomics; microbial composition; microbiome; microbiome composition; mouse allergy; mouse model; novel; novel marker; novel therapeutic intervention; oral tolerance; resistin; response; skills; symposium; targeted treatment

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.

项目总结/摘要： 研究：食物过敏是一种潜在的危及生命的健康状况，影响越来越多的人， 仅在美国的个人。目前对食物过敏患者的日常管理受到 缺乏可靠的生物标志物来准确预测疾病的发作、严重程度和消退， 缺乏治疗方法来取代严格避免罪魁祸首食物。更深入地了解其他 在食物过敏发病机制中起作用的IgE以外的其他机制将是填补这些空白的关键。这项建议 详细介绍了一个五年计划，为Crestani博士提供培训和专业知识，以评估CIMb的作用， 一种新的生物标志物和分子球员在食物过敏建设和扩大强初步 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 食物过敏中的抗组胺抗体的作用，有希望确定强烈需要的疾病生物标志物（S） 和治疗干预的可能目标，这将是未来纵向研究的重点， 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：Crestani博士的长期目标是成为一名独立的，NIH资助的研究者，专注于 食物过敏的疾病机制和生物标志物，目的是改善目前的次优护理， 食物过敏的人。对新的生物标志物和治疗方法存在迫切且未满足的需求 食物过敏为了实现这一目标，她的短期目标是获得生物统计学、数据 分析，实验室技术，以及在队列建设和管理的实践技能。这将是 通过正式课程、协作工作、参加会议和既定指导完成 具有相关专业知识的导师/科学顾问。这将导致实践技能的独特组合， 科学知识，这将成功地定位她的R 01应用程序和独立的职业生涯，作为一个 食物过敏领域的医生兼科学家 环境：Crestani博士将由Chatila博士（主要导师）指导，Chatila博士是以下领域的主要研究者： 食物过敏的机制和一个完全由NIH资助的实验室的负责人，Phipatanakul博士（共同导师），一个 流行病学、人类队列和哮喘及过敏性疾病临床研究专家。克雷斯塔尼医生 组建了一个由顾问组成的非凡团队，包括琳达·施耐德博士、卡莉·纳多博士和瑞玛博士 Kaddurah-Daouk，他们投入了时间，资源和专业知识来促进Crestani博士的职业生涯 发展和顺利完成拟议项目。在此期间，Crestani博士将 通过哈佛公共卫生学院（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。导师们创造的学术环境， 整个机构和哈佛社区将为学习和研究提供理想的环境 能保证克雷斯塔尼医生成为一名非常成功的独立调查员