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My lab studies the molecular machines involved in vesicular traffic, a fundamental process utilized by all compartmentalized cells from yeast to man to move proteins between different membranous compartments. Our initial interest in this subject grew out of our efforts to dissect the molecular mechanisms underlying synaptic transmission. We showed that the clathrin pathway is essential for synaptic vesicle recycling. We went on to characterize the mechanisms of clathrin polymerization and uncoating that underlie this process. The uncoating reaction is promoted by the chaperone protein Hsc70, which is a member of the Hsp70 family of chaperone proteins. These chaperone proteins are also involved in many aging related disorders that are a consequence of the accumulation of damaged, aggregated proteins (Alzheimer's, ALS, Parkinson's, Huntington's, and others). Therefore we are also interested in understanding the roles these chaperones play in both protein aggregation diseases and cancer during the aging process. We utilize a combination of biochemical and physiological approaches including solution biochemistry (surface plasmon resonance, dynamic light scattering, analytical ultracentrifugation, nuclear magnetic resonance spectroscopy), X-ray crystallography, and electrophysiology. Our work has broad significance since chaperones are involved in many macromolecular complex remodeling reactions.
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