Research Interests:

Living cells constantly monitor and respond to their environment by detecting interactions between cell-surface receptors and their ligands. We are interested in the molecular mechanisms by which specific signals are received and transmitted by cell-surface receptors. Active components of receptors and ligands are expressed and their properties studied by both biochemical and X-ray crystallographic methods. These studies are designed to provide a molecular basis for understanding the behavior of specific molecules in living systems.

We are currently pursuing studies in three related systems. In collaboration with the laboratories of Phil Beachy and Jeremy Nathans here at Hopkins, we are investigating the molecular mechanisms employed by specific signaling pathways during animal development. In particular, we have determined the crystal structures of components of both the Hedgehog and Wnt signaling pathways as well as complementary biochemical and mutagenesis studies. We are pursuing studies of additional molecules involved in each of these pathways and hope to develop an understanding of the molecular events that take place at each step in the signaling cascade. Developmental signaling pathways are of particular interest because signaling during animal development must be restricted in time and place, and the molecular features of these pathways often reveal unique solutions to this problem. Defects in these signaling pathways are frequently found in human diseases including many forms of cancer, and understanding these pathways
may have important implications for human health.

We are also pursuing studies of members of the epidermal growth factor receptor (EGFR) families as well as molecules involved in axon guidance. Each of these systems presents interesting questions concerning the nature of interactions between receptors and ligands, how these interactions are regulated, and how these interactions are integrated to build and maintain a living organism. Study of these systems invariably establishes unexpected links to other signaling pathways thatprovide insight into the function and evolution of these molecules.