Research InterestsCytokine Receptor Signaling, Apoptosis, Allergy, and Asthma, and myeloid cell functionLymphocyte activation and clonal expansion forms the basis of a productive immune response to an antigenic challenge and often involves the collaboration between B and T cells. These processes are highly regulated by several factors, including cytokines. Interleukin-4 (IL-4) is a cytokine produced by T cells, mast cells, eosinophils, and basophils that has profound effects on immune regulation. These effects include the ability to regulate IgE production and the ability to act as a viability factor and a growth co-factor for B cells, T cells, and mast cells. IL-4 also regulates the lymphokine- producing phenotype of CD4+ helper T cells and the type of immune response elicited by a given pathogen (i.e. cell-mediated or antibody). This immune regulation can determine the type of immune response elicited by an antigenic challenge such as a transplanted tissue. The major goal of our lab is to gain an understanding of the molecular mechanism by which IL-4 mediates these effects with the future goal of developing rational strategies for manipulating immune responses. Our recent efforts have focused on understanding the structure of the receptor for IL-4 and the signal transduction pathways activated in cells by the binding of IL-4 to its receptor. We analyze three major signal transduction pathways activated by the IL-4 receptor through the tyrosine kinases JAK1 and JAK3 including the Shc, STAT-6, and IRS pathways. We are focusing on understanding how these signaling pathways lead to the regulation of gene expression, cell proliferation, and the suppression of caspase activation leading to the protection from apoptosis. An additional major focus is to understand how these pathways contribute to the pathogenesis of allergic asthma in a mouse model. Furthermore, we are studying the mechanism by which IL-4 regulates the development and function of myeloid cells, including macrophages and osteoclasts. Publications
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