Poster Abstract

Spring 2012 Biomedical Seminar Series

“Using small molecule inhibitors to understand immune function: blocking allergies and finding targets”

Avery August Professor of Immunology
Cornell University Ithaca, NY

Abstract Mast cells are immune cells that play a critical role in the development of the allergic response. Upon activation by allergens and IgE via the Fc?RI, these cells release histamine and other pharmacological agents that initiate and propagate immediate hypersensitivity reactions. Mast cells also secrete cytokines that can regulate immune activity. These processes are controlled in whole or part by increases in intracellular Ca2+ induced by the Fc?RI. This lecture will discuss our work characterizing a small molecule immunosuppressant 3,5-bistrifluoromethyl pyrazole (BTP), a pyrazole derivative, which inhibits mast cell function. We will present our structure activity relationship analysis BTP derivatives indicating that the trifluoromethyl group at the C3 position is important for its activity. We will also discuss the identification of a target of BTP as the actin binding protein drebrin using chemico-genomic approaches. Finally, we will discuss genetic knockout of drebrin in transgenic mice and analysis of its role in mast cell function and the allergic response in vivo.

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