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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总结/摘要这个K23提案包括一个为期五年的职业发展计划，旨在领导查尔斯F。舒勒四世，医学博士成为一名独立的医生科学家，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和临床免疫学医生科学家，提高食物过敏的诊断和治疗的长期目标。这个建议是建立在舒勒博士的实验室和临床研究的经验，并利用现有的人类生物样品库，接受口服食物挑战的食物过敏受试者，食物过敏诊断的金标准。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继续进行免疫学和玛丽H.威瑟食物过敏中心，结合詹姆斯R。Baker Jr，医学博士和尼古拉斯·W.卢卡奇博士拥有一个杰出的顾问委员会。舒勒医生会按照计划正式的课程，专业发展和指导研究，成功成长为一个独立的医学科学家。这项指导研究包括2个科学的具体目标研究目的1：确定FLG、SPINK 5和JAM-A中屏障基因变异体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。通过完成这些总体目标，舒勒博士将（1）评估已知和未知变异在这些关键的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过敏反应，同时寻求构建食物过敏的多基因风险评分;（3），定义反式- 表皮水分流失，以确定患者的食物过敏反应的风险;和（4）发展经表皮水分流失作为食物挑战期间过敏反应的实时临床测量。这里建立的研究的纲领性路线将导致R 01提案的几个机会。在此外，该提案的结果将使用密歇根州东南部食物过敏症协作出生队列，目前正在开发的大规模生物储存库。这项工作也可以导致开发非侵入性食物过敏风险概况，以最大限度地减少昂贵，繁琐和危险的需要食物挑战此外，通过这项工作，舒勒博士将发展广泛适用于以下领域的研究技能：许多不同领域的过敏研究。因此，这个K23奖项将支持并大大加速职业生涯将舒勒博士培养成一名成功、创新和独立的研究者。