| Position: Professor
Degrees: MD, PhD
Office Phone: 434-924-5108
Messenger Mail: PO Box 800736
The ultimate goal of our studies is to gain a deeper understanding of the molecular basis for important human diseasessuch as sudden death, myocardial infarction, rotavirus infection and HIV infection that cause substantial mortality and suffering. The structural details revealed by our work may provide clues for the design of more effective and safer medicines.
At the basic science level, we are intrigued by biological questions at the interface between cell biology and structural biology. How do membrane channels open and close? How are signals transmitted across a cellular membrane when an extracellular ligand binds to a membrane receptor? How do viruses attach and enter host cells, replicate and assemble infectious particles?
In our laboratory we use high resolution electron cryo-microscopy (cryo-EM) and image processing to explore the molecular design of large, multicomponent supramolecular assemblies. Biological specimens are quick frozen in a physiological state to preserve their native structure and functional properties. A special advantage of this rapid-freezing method is that we can trap and image dynamic states of functioning macromolecular assemblies, such as open and closed states of membrane channels and viruses actively transcribing RNA. Three-dimensional density maps are obtained by digital image processing of the high-resolution electron micrographs. The rich detail in the maps reveals the structural organization of complex biological structures that can be related to the functional properties of such assemblies.
Research projects underway include the structure analysis of:
(1) Membrane proteins involved with cell-to-cell communication (gap junctions), water transport (aquaporins), ionic transport (potassium channels), transmembrane signaling (integrins), and viral recognition (rotavirus NSP4)
Restenosis after Coronary Artery Angioplasty and Stent Placement :