David M Smith

Biography

Works as Associate Professor in Biochemistry

Research Interest

The general interest of our lab is to understand the function of the proteasome, a giant molecular machine that has the capacity to destroy nearly every protein in the cell. Despite this destructive capability the proteasome is highly selective in what it chooses to destroy. In fact, this machine is so selective and precise that it can degrade a single subunit out of a protein complex with surgical precision, or can amputate a single domain from an isolated protein. Ultimately, our lab is interested in understanding how the proteasome moves and functions at a molecular level, using an energy dependent multistep process involving 1) substrate binding, 2) unfolding, 3) translocation, 4) gate-opening and 5) destruction inside of a sequestered chamber. More specifically we have a special interest in understanding how the many different regulatory “caps” that bind to the 20S proteasome catalyze aspects of this multistep process. Because of the proteasome’s central role in regulating most cellular processes (e.g. Cell cycle, Apoptosis, transcription, receptor signaling, etc.) understanding the mechanisms that regulate its specificity is not only of biological interest, but is also highly relevant to many areas of medicine (e.g. Cancer and Neurodegenerative disease).