Cells are able to integrate an enormous array of environmental information and convert these signals into complex behaviors such as growth, differentiation, and motility. This relay of extracellular stimuli into a phenotypic response involves the transfer of information through complex signal transduction networks that are precisely regulated, both spatially and temporally. Determining how these signal transduction networks are able to turn simple inputs into complex behavior is one of the greatest challenges in modern biology and will provide valuable insight into the cause and treatment of human diseases such as cancer, diabetes, and inflammation.
Our group is interested in developing new chemical tools that will allow a greater quantitative understanding of cellular signaling than is possible with currently available methods. Using the tools of organic synthesis we are generating cell permeable small molecules that allow the activation or inactivation of specific signaling enzymes in living cells. While we are interested in studying the function of a number of protein families that are involved in signaling, our initial efforts will focus on enzymes that mediate intracellular phosphorylation (the protein kinases and phosphatases). These studies will focus on three main areas: 1) The location-specific function of kinases and phosphatases. 2) The quantitative characterization of specific intracellular phosphorylation events. 3) The conformational plasticity of signaling enzymes.