The role of epithelial barrier dysfunction in food anaphylaxis

上皮屏障功能障碍在食物过敏反应中的作用

基本信息

批准号：
10670901
负责人：
Charles F Schuler
金额：
$ 19.44万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-25 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10670901
关键词：
Acceleration Acute Affect Allergic Allergic Reaction Allergy to peanuts Anaphylaxis Anxiety Area Biological Markers Birth Blood Cells Child Clinical Clinical Immunology Clinical Research Data Data Set Development Diagnosis Diagnostic Disasters Disease Doctor of Philosophy Eating Enhancers Environment Eosinophilic Esophagitis Epinephrine Epithelium Esophagus Food Food Hypersensitivity Functional disorder Genes Genomics Goals Growth Human Hypersensitivity Hypersensitivity skin testing IgE Immune Immune system Immunology Impairment Incidence Individual Inflammatory Ingestion Intestinal permeability Laboratory Research Lead Learning Life Measurement Measures Medical Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Methods Michigan Modality Monitor Mucous Membrane Mus Oral Oral cavity Outcome Pathogenesis Pathogenicity Patients Permeability Persons Physicians Population Predictive Value Program Development Promoter Regions Protease Inhibitor Proteins Reaction Research Research Personnel Risk Role Safety Sampling Scientist Serine Serology test Severities Skin Symptoms Testing Tight Junctions Time Training United States Universities Variant Water Work biobank biomarker discovery career development clinical application cohort cost design diagnostic tool dietary exome sequencing experience filaggrin food allergen food avoidance food challenge food standard genetic variant genomic data immune activation improved in vivo innovation junctional adhesion molecule nutrition outcome prediction polygenic risk score real time monitoring secondary outcome skills skin barrier

项目摘要

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.

标题：上皮屏障功能障碍在食物过敏反应中的作用项目概要/摘要这项 K23 提案包括旨在领导查尔斯·F·舒勒四世 (Charles F. Schuler IV) 的五年职业发展计划，作为一名独立的医学科学家，研究食物过敏、粘膜免疫学、舒勒博士是一位过敏和临床免疫学医师科学家，拥有长期的研究经验。改善食物过敏的诊断和治疗的长期目标该提案建立在舒勒博士的基础上。实验室和临床研究经验，并利用现有的人类生物样本库食物过敏受试者接受口服食物挑战，这是食物过敏诊断的金标准。将在密歇根大学过敏/临床部门丰富的培训环境中进行免疫学和 Mary H. Weiser 食物过敏中心，结合 James R. Baker Jr 医学博士的共同指导尼古拉斯·W·卢卡奇 (Nicholas W. Lukacs) 博士和杰出的研究顾问委员会将遵循一项计划。正式课程、专业发展和指导研究，以成功成长为独立医师科学家。这项指导性研究包括 2 个科学具体目标目标 1：确定 FLG、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：检验净皮肤屏障测量预测或测量口腔食物的能力挑战结果。通过完成这些总体目标，舒勒博士将 (1) 评估已知和未知的变异在 (2)、识别导致食物的额外屏障相关基因 (3)、定义反式能力表皮失水，以识别有食物过敏风险的患者；(4) 发生经表皮失水；作为食物挑战期间过敏反应的实时临床测量。这里建立的计划性研究路线将为 R01 提案带来一些机会。此外，该提案的研究结果将使用东南密歇根食物过敏进行验证协作出生队列是一个正在开发的大型生物样本库，这项工作也可以导致这一结果。开发非侵入性食物过敏风险概况，以最大限度地减少昂贵、繁琐和有风险的治疗的需要此外，舒勒博士将通过这项工作发展广泛适用于口腔食物的挑战。因此，这个 K23 奖项将支持并极大地促进其职业生涯。将舒勒博士发展成为一名成功的、创新的、独立的研究者。