Summary of Research

Research in our laboratory concerns the atomic-level structure and mechanism of the enzymes and molecular switches that carry out cellular signal transduction. Our laboratory, which in the past has also made major contributions to research in DNA replication, uses X-ray crystallography to determine the three-dimensional structures of proteins involved in signaling and replication, as well as biochemical, biophysical, and computational analyses to elucidate mechanisms. Breakthroughs from our lab have included figuring out the workings of proteins known as tyrosine kinases, which are switches that often go awry in cancer. Our group has provided substantial contributions to the fundamental understanding of the structure of these switches, leading to explanations for how the cancer drug Gleevec achieves specificity and how the catalytic activity of the epidermal growth factor receptor, which malfunctions in many cancers, is switched on. In addition, much of our current understanding of the structural mechanisms of how high speed DNA polymerases achieve very high processivity also emerged from our group.
Cell Signaling
DNA replication