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We are interested in the molecular details of how cells survive by recognizing and responding to intracellular signals. Eukaryotic cells employ several mechanisms to maintain homeostasis, and if these systems are mis-regulated, changes in metabolite concentrations or protein production/folding eventually lead to a host of diseases. In addition, some of these pathways exist in and are exploited by bacterial pathogens and viruses to gain entry into eukaryotic cells. We seek to understand the details of structure, function, and mechanism of proteins involved in these highly regulated pathways, focusing on enzymes that perform hydrolysis reactions in an unexpected chemical environment: within lipid membrane or near the surface of membranes. In the long term, we hope to identify small molecule inhibitors to modulate these activities and prevent diseases associated with aberrant signaling behavior.
Our methods focus on protein crystallography, biochemical and biophysical characterization, in silico modeling, and drug design.