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Structural Biology of Signal Transduction

Our research interests focus on proteins that are involved in signal transduction pathways of the innate immune system. The human immune system is generally divided into two broad categories, the adaptive immune system and the innate immune system. Adaptive immunity relies on a very large repertoire of clonally distributed antigen receptors displayed on lymphocytes and secreted antibodies that have the ability to recognize almost any foreign molecule. Conversely, innate immunity depends on a limited set of germ-line encoded receptors, which recognize distinct molecular patterns on pathogen surfaces. These receptors are strategically expressed on cells that are likely to encounter antigen early in an infection, including cells of the respiratory tract, epithelial cells of the gut and skin, and professional antigen presenting cells. As a result, the innate immune response generally precedes the adaptive immune response.

Specifically, our lab studies components of the Toll-like receptor (TLR) signal tranduction pathway, including the TLR receptors themselves and members of the Interleukin-1 receptor associated kinase (IRAK) family using X-ray crystallography and other biophysical techniques. Using structural analysis, we would like to dissect the molecular basis for specificity of TLR-ligand interactions and the mechanisms by which the IRAKs are regulated. It is hoped that by visualizing the atomic-level details of these proteins and the interactions they make, we can contribute to potential therapies against infectious diseases and autoimmune disorders.