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.
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.
| Kim, Alexander S; Doherty, Taylor A (2016) New and emerging therapies for asthma. Ann Allergy Asthma Immunol 116:14-7 |
| Doherty, T A; Broide, D H (2015) Group 2 innate lymphoid cells: new players in human allergic diseases. J Investig Allergol Clin Immunol 25:1-11; quiz 2p following 11 |
| Doherty, Taylor A (2015) At the bench: understanding group 2 innate lymphoid cells in disease. J Leukoc Biol 97:455-67 |
| Doherty, Taylor A; Baum, Rachel; Newbury, Robert O et al. (2015) Group 2 innate lymphocytes (ILC2) are enriched in active eosinophilic esophagitis. J Allergy Clin Immunol 136:792-794.e3 |
| Kim, Hee-Kyoo; Lund, Sean; Baum, Rachel et al. (2014) Innate type 2 response to Alternaria extract enhances ryegrass-induced lung inflammation. Int Arch Allergy Immunol 163:92-105 |
| Walford, Hannah H; Lund, Sean J; Baum, Rachel E et al. (2014) Increased ILC2s in the eosinophilic nasal polyp endotype are associated with corticosteroid responsiveness. Clin Immunol 155:126-35 |
| Chang, Jinny E; Doherty, Taylor A; Baum, Rachel et al. (2014) Prostaglandin D2 regulates human type 2 innate lymphoid cell chemotaxis. J Allergy Clin Immunol 133:899-901.e3 |
| Miller, Marina; Rosenthal, Peter; Beppu, Andrew et al. (2014) ORMDL3 transgenic mice have increased airway remodeling and airway responsiveness characteristic of asthma. J Immunol 192:3475-87 |
| Doherty, Taylor A; Scott, David; Walford, Hannah H et al. (2014) Allergen challenge in allergic rhinitis rapidly induces increased peripheral blood type 2 innate lymphoid cells that express CD84. J Allergy Clin Immunol 133:1203-5 |
| Walford, Hannah H; Doherty, Taylor A (2014) Diagnosis and management of eosinophilic asthma: a US perspective. J Asthma Allergy 7:53-65 |
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