Role of Lung Inflammation in Th2 Priming

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DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in Allergy and Immunology. The principal investigator has completed an M.D. at Temple University, residency training in Internal Medicine at Yale University School of Medicine and is currently completing an Allergy and Clinical Immunology fellowship at the same institute. This program will allow the candidate to expand on her previous scientific skills and to become proficient in the fields of asthma pathogenesis and Th2 priming. Dr. Kim Bottomly will mentor the principal investigator's scientific development. Dr. Bottomly is a recognized leader in the field of asthma pathogenesis. Dr. Bottomly is a Professor of Immunobiology and has successfully trained numerous postdoctoral fellows and graduate students. Research will focus on the mechanisms by which Th2 inflammation affects priming of naive CD4 T cells to new environmental antigens. This process occurs by a mechanism distinct from that responsible for Th2 priming in a naive mouse and may occur independently from the innate immune system. Our preliminary data show Th2 cytokines produced during inflammation lead to priming of a new population of Th2 effector cells. The specific aims include: 1) investigation of the role of IL-4 in this model. 2) identification of the target cell upon which IL-4 acts. 3) investigation of the role of IL-13 and identification of the cell upon which IL-13 acts. Asthma is a growing epidemic in developed nations with a huge impact in morbidity and mortality. If we understand the pathogenesis we will be able to apply this to patient care. Our hope is to learn enough to prevent asthma before it develops. This K08 award will greatly assist the candidate's research into asthma pathogenesis and mechanisms of inflammation and provide her with time and resources to develop into a skilled independent investigator.