Cancer is most commonly caused by the development of aberrant cell signaling pathways. Modern pharmaceutical research thus seeks a clear understanding of these pathways in efforts to treat this all too prevalent illness. A major focus in our laboratory is ERK, a striking mitogen-activated protein kinase that regulates cellular processes with remarkable efficiency and specificity. MAP kinases are mediators of numerous cellular signals, and are believed to play major roles in tumor formation and progression to metastasis. The mitogenic pathway most important in the pathogenesis of human cancer contains the Ras->Raf->MEK->ERK module. Students with an interest in integrating the disciplines of chemistry and biochemistry in the search for treatment of human disease are strongly encouraged to join us by applying. We employ a chemical-biology approach in efforts to elucidate the biochemical basis for the regulation and mechanism of protein kinases. Using state-of-the-art enzyme kinetic techniques we have uncovered surprising mechanisms of substrate recognition. We are currently applying structural methods to address some of the questions posed by these studies. Using high through-put screening, coupled to chemical and peptide library approaches, we are developing small molecule and peptide inhibitors of protein kinases. These inhibitors will be used to elucidate the roles of kinases in cancer progression. Soon, small-molecule inhibitor design will be complimented through virtual screening efforts. More recently, we have begun to develop new chemical-biology tools, in order to interrogate protein kinase pathways in living cells. Here, our mechanistic knowledge is crucial for the development of fluorescent sensors and inhibitors that will be delivered into living cells. The potential for cancer treatment through the targeting of protein kinase remains largely untapped. Our laboratory endeavors to identify these treatments by utilizing novel efforts in chemical biology.