David P. Siderovski
School of Medicine
Area of interest
In 1996, our group discovered a new family of signal transduction regulatory proteins, the "regulators of G-protein signaling" (RGS) proteins. RGS proteins increase the intrinsic GTP-hydrolyzing activity of G-protein alpha subunit in vitro, and are therefore considered to act in vivo to inhibit signaling from ligand-stimulated G protein-coupled receptors. We are currently investigating two members of the RGS protein family, RGS12 and RGS14, that additionally interact with small GTPases of the Ras-superfamily -- indications are that these two RGS proteins integrate and coordinate signaling from receptor tyrosine kinases and G-protein coupled receptors.
Awards and Honors
Winner of the 2006 Phillip and Ruth Hettleman Prize for Artistic and Scholarly Achievement.
Winner of the 2004 John J. Abel Award for the outstanding American pharmacologist under 40 from the American Society for Pharmacology and Experimental Therapeutics
We recently discovered a new class of proteins, the GoLoco proteins, that modulate the guanine nucleotide cycle of G-protein alpha subunits in a manner independent of classical RGS-box GAP activity. We found that GoLoco proteins bind and inhibit the spontaneous release of guanine nucleotide by GDP-bound G-alpha subunits. Emerging genetic evidence from model organisms such as the fruitfly Drosophila melanogaster and the nematode worm Caenorhabditis elegans suggest that GoLoco proteins couple G-alpha-i subunits to spindle force generation during microtubule formation and chromosomal separation at mitosis. We recently published our findings regarding C. elegans GoLoco proteins in Science and Cell and are currently pursuing the hypothesis that human GoLoco proteins will serve as excellent drug discovery targets for modulating microtubule dynamics during cancer chemotherapy.