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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