Research Interests

Cell surface receptor-ligand recognition and activation in systems relevant to human health and disease

Cell surface receptors represent the gateway through which the cell senses and responds to its environment. Most physiologically important processes are initiated by the interaction of cell-surface receptors with extracellular mediators. This recognition event is communicated across the membrane, resulting in activation of intracellular signal transduction cascades. Molecular insight into recognition and activation of receptors implicated in human disease could reveal new strategies, or better inform current strategies, for therapeutic intervention using protein engineering. In this way, our structural and mechanistic studies inform translational efforts to exploit this information into the therapeutic realm. We view structural information on receptor-ligand complexes as molecular blueprints to then allow us to penetrate the biology of these systems for both basic and practical advances.

Thematically, we are interested in shared receptors that appear to differentially respond to multiple ligands, and protein-protein interaction systems that play central roles in Immunology, Neurobiology, and Development. In addition to understanding basic aspects of receptor signaling and structural biology, we are also interested in the creation of novel receptor ligands using protein engineering, and deorphanization of new ligand-receptor systems using proteomics. A major forward thrust of our laboratory is to synthetically leverage natural biological signaling mechanisms in such a way as to alter and manipulate cell fate and function.

We approach our studies using a range of methodologies including protein biochemistry, protein engineering, combinatorial biology, X-ray crystallography, proteomics, cell biology, electron microscopy and a wide range of in vitro and in vivo translational approaches.