We are interested in the stereochemical details of the intermolecular interactions in signal transduction pathways.
1.  Ligand induced activation of receptor tyrosine kinases (RTKs). Activation of RTKs leads to a host of downstream signaling events that result in a variety of different cellular responses, including stimulating growth. Inappropriate receptor activation can lead to cancer, and understanding how these receptors function is of significant biomedical importance. Recent advances have led to the proposal of a novel mechanism for activation of the epidermal growth factor (EGF) receptor. We are investigating the implications of this model for activation and inactivation of EGF receptor and other RTKs.
2.  Protein-protein interactions in intracellular signaling. It is clear that formation of large mulitmolecular assemblies plays a key role in controlling intracellular signaling, trafficking and other processes. We are using X-ray crystallography to determine the structures of key complexes, and a variety of biophysical techniques to study such assembly formation in vitro.