Research in our group is focused on the biophysics of macromolecular interactions; principally, how do the structure and dynamics of macromolecules allow interactions to proceed with particular affinities, specificities, kinetics, and environmental dependencies? As these properties ultimately dictate biological activity, the lab is also interested in the relationships between macromolecular biophysical chemistry and biology. An understanding of the biophysics of macromolecular interactions is crucial for the developing field of structure-based drug design, prediction of binding sites and properties from structural or sequence databases, and dissecting the nuances of complex, multi-subunit protein machines and signaling pathways.

Our primary focus is on two important molecules in the immune system: T-cell receptors (TCRs) and their ligands, small peptides bound and "presented" by class I or class II major histocompatibility molecules (peptide/MHCs). These molecules form the foundation of the cellular arm of the mammalian immune system. Detailed studies of macromolecular interactions in the immune system will aid in our understanding of the role of the immune system in health and disease, including such areas as the response to foreign pathogens and cancer immunosurveillance. Furthermore, it will contribute to efforts to design immunologically-based therapeutics and interventions for diseases such as autoimmunity and cancer.

Our laboratory uses primarily structural and biophysical appraoches. We combine the techniques of structural biology (macromolecular X-ray crystallography and NMR) with biophysical methods such as titration calorimetry, surface plasmon resonance, fluorescence spectroscopy, and analytical ultracentrifugation. We also use a number of computational approaches (continuum electrostatics, molecular modeling, and molecular dynamics). We work closely with immunologists at the National Institutes of Health who investigate a variety of immunological phenomena. Our overall goals are to integrate structural, biophysical, and immunological data to generate useful descriptions of how molecular interactions modulate immune reactivity.