Mark Swingle, Ph.D.
Associate Professor
Postdoctoral Studies: ÐÓ°ÉÂÛ̳
Ph.D.: ÐÓ°ÉÂÛ̳
Research Interests
Protein phosphatase function and regulation. Assay/screening development and ligand discovery.
Reversible phosphorylation of structural and regulatory proteins plays a crucial role in the regulation of many cellular functions in eukaryotes, affecting a large and diverse panoply of cellular processes. Phosphorylation occurs principally upon serine, threonine, and tyrosine residues and is mediated by members of an extremely large group of ser/thr- and tyr-protein kinases, which catalyze the transfer of a gamma phosphate from ATP to the side chain hydroxyl. Dephosphorylation is accomplished by one or more of the >150 ser/thr-, tyr-, or dual-specificity phosphatases, which catalyze the hydrolysis of seryl, threonyl, and/or tyrosyl phosphomonoesters, respectively. The biological activity of a protein, its location within a cell, its stability, and interactions with other macromolecules can all be affected by its phosphorylation state, which is governed dynamically via coordinated regulation of the kinases and phosphatases that utilize it as a substrate.
My laboratory is currently focused upon two members of the PPP family of protein phosphatases: PP5, a key part of the HSP90 chaperone machinery, and PP2A, one of the most abundant cellular phosphatases, which is subject to very complex regulation via assembly into a bewildering variety of functional heterotrimeric holoenzymes. Through our studies we hope to develop a better understanding of the cellular functions of these phosphatases, the mechanisms by which they are regulated, and their potential roles in various disease processes. In addition, my laboratory has an abiding interest in pursuing ligand discovery efforts aimed at developing novel type-specific inhibitors and activators of PPP phosphatases as research tools and/or potential leads for drug development