The role of epithelial barrier dysfunction in food anaphylaxis

标题：上皮屏障功能障碍在食物过敏反应中的作用 项目摘要/摘要 这份K23提案包括一项为期五年的职业发展计划，旨在领导查尔斯·F·舒勒四世， 作为一名内科科学家，研究食物过敏、粘膜免疫学、 和上皮屏障功能。舒勒博士是一位过敏症和临床免疫学内科科学家，长期- 改善食物过敏诊断和治疗的长期目标。这项建议建立在舒勒博士的 在实验室和临床研究方面的经验，并利用现有的人类生物库样本来自 食物过敏受试者接受口腔食物挑战，这是食物过敏诊断的黄金标准。这项建议 将在密歇根大学过敏/临床分部丰富的培训环境中进行 免疫学和玛丽·H·威瑟食物过敏中心，结合小詹姆斯·R·贝克医学博士的共同指导 尼古拉斯·W·卢卡奇(Nicholas W.Lukacs)，拥有杰出的调查顾问委员会的博士。舒勒博士将遵循一项计划 正规课程、专业发展和有指导的研究，以成功地成长为 独立的内科科学家。 这项指导性研究包括两个具体的科学目标 目标1：确定Flug、Spink5和Jam-A中屏障基因变异在食物过敏中的作用 发展。 目标2：检查净皮肤屏障测量预测或测量口服食物的能力 挑战结果。 通过完成这些首要目标，舒勒博士将(1)评估已知和未知的变量在 这些关键屏障基因有助于食物过敏；(2)识别导致食物过敏的其他屏障相关基因 寻求构建食物过敏的多基因风险评分；(3)定义反式-反式反应的能力 表皮水分丢失，以确定有食物过敏风险的患者；以及(4)发展为经表皮水分丢失 作为食物挑战期间过敏反应的实时临床测量。 在这里建立的方案研究路线将导致R01提案的几个机会。在……里面 此外，这项提案的发现将使用密歇根州东南部的食物过敏进行验证 协作性出生队列，这是一个正在开发的大规模生物信息库。这项工作还可以导致 开发非侵入性食物过敏风险概况，以最大限度地减少对昂贵、繁琐和高风险的需求 口腔食物挑战。此外，通过这项工作，舒勒博士将开发广泛适用于以下领域的研究技能 过敏研究的许多不同领域。因此，这个K23奖项将支持并极大地促进职业生涯 将舒勒博士发展成为一名成功、创新和独立的研究员。

Title: The role of epithelial barrier dysfunction in food anaphylaxis Project Summary/Abstract This K23 proposal comprises a five-year career development program designed to lead Charles F. Schuler IV, MD into independence as a physician scientist studying the confluence of food allergy, mucosal immunology, and epithelial barrier function. Dr. Schuler is an allergy and clinical immunology physician scientist with a long- term goal of improving the diagnosis and treatment of food allergy. This proposal builds on Dr. Schuler's experiences in laboratory and clinical research and leverages an existing human biorepository of samples from food allergy subjects undergoing oral food challenges, the gold standard of food allergy diagnosis. This proposal will proceed within the rich training environment at the University of Michigan Division of Allergy/Clinical Immunology and Mary H. Weiser Food Allergy Center, combining the co-mentorship of James R. Baker Jr, MD and Nicholas W. Lukacs, PhD with an outstanding advisory board of investigators. Dr. Schuler will follow a plan of formal coursework, professional development, and mentored research to successfully grow into an independent physician scientist. This mentored research includes 2 scientific Specific Aims  Aim 1: Determine the role of barrier gene variants in FLG, SPINK5, and JAM-A in food allergy development.  Aim 2: Examine the ability of net skin barrier measurements to predict or measure oral food challenge outcomes. Through completing these overarching Aims, Dr. Schuler will (1) evaluate how known and unknown variants in these key barrier genes contribute to food allergy; (2), identify additional barrier-related genes that lead to food anaphylaxis while seeking to construct a polygenic risk score for food allergy; (3), define the ability of trans- epidermal water loss to identify patients at risk of food anaphylaxis; and (4) develop trans-epidermal water loss as a real-time clinical measurement of anaphylaxis during food challenges. The programmatic line of research established here will lead to several opportunities for R01 proposals. In addition, the findings from this proposal will be validated using the Southeast Michigan Food Allergy Collaborative birth cohort, a large-scale biorepository that is now in development. This work can also lead to the development of non-invasive food allergy risk profiles to minimize the need for costly, cumbersome, and risky oral food challenges. Further, through this work Dr. Schuler will develop research skills broadly applicable to many different areas of allergy research. Thus, this K23 award will support and greatly accelerate the career development of Dr. Schuler into a successful, innovative, and independent investigator.