This proposal describes a 5 year training program for the development of an academic career in laboratory medicine. The principle investigator has completed structured internal medicine residency and allergy/immunology fellowship training at the University of California at San Diego and has been appointed as an Assistant Professor. He will expand upon his scientific skills through a focused career development plan and training in T cell costimulation as applied to chronic allergen-induced airway inflammation and remodeling. Dr. David Broide is a professor of medicine at UC San Diego and will mentor the principle investigator's scientific development. Dr. Broide is a recognized leader in mechanisms of airway inflammation and remodeling and has a strong record of mentoring developing physician scientists. An advisory committee of scientists, including Dr. Michael Croft who has expertise in T cell biology and costimulation, will provide career and project guidance. In addition, related course work, seminars, journal clubs, and specific laboratory technique training will accompany ample protected research time in a supportive academic environment in the Department of Medicine at UCSD. The research project will focus on the role of costimulatory molecules in chronic allergen-induced airway inflammation and remodeling. Dr. Croft's laboratory at La Jolla Institute for Allergy and Immunology has discovered a critical role for the TNFR family member OX40 in acute allergen induced airway inflammation, as well as in TH2 memory responses. The proposed studies will test the critical roles of OX40/OX40 ligand interactions in a chronic allergen-induced murine model of asthma and airway remodeling through knockout, antibody- blocking, adoptive transfer, and imaging studies. Additionally, we will evaluate the role of OX40 on TH2 cells and cross talk with eosinophils and bronchial epithelial cells expressing OX40L. Finally, we will determine the expression of OX40 and OX40L in human asthmatic peribronchial samples and evaluate allergen specific OX40-mediated TH2 responses, including key signaling events, from peripheral blood. These studies have direct significance for understanding the mechanisms of chronic asthma and may reveal therapeutic targets. Importantly, asthma affects 7% of people in the United States and prevalence has increased dramatically over the past few decades.

Public Health Relevance

These studies have direct significance for understanding the mechanisms of chronic asthma and may reveal therapeutic targets. Importantly, asthma affects 7% of people in the United States and prevalence has increased dramatically over the past few decades.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI080938-03
Application #
8305053
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
2010-08-16
Project End
2015-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$132,300
Indirect Cost
$9,800
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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