Van Liere Professor and Chair, WVU
Dept. of Physiology and Pharmacology
West Virginia University School of Medicine
B.Sc., Queens University in Ontario, Canada
Ph.D., University of Toronto, Canada
Phone: (304) 293-4991
Science Blog: http://dsiderovski.wordpress.com
Molecular control of the timing and intensity of hormonal signaling, and its derangement in disease states
David P. Siderovski, Ph.D. became Chair of West Virginia University’s Department of Physiology and Pharmacology in July 2012. His group’s long-standing research focus has been regulators of heterotrimeric G-protein signaling, having discovered the G-alpha GAP superfamily (“RGS proteins”) in 1996 based on genome sequence mining and yeast complementation. In 1999, Dr. Siderovski also discovered the GoLoco motif protein family of G-alpha•GDP dissociation inhibitors. Since these discoveries, his research into the function of novel regulators in G-protein signal transduction has led to over 120 papers, reviews, and book chapters on the topic, as well as three different new investigator awards: a Year 2000 EJLB Neuroscience research scholarship, a 2001 New Investigator Award in the Basic Pharmacological Sciences from the Burroughs-Wellcome Fund, and (in 2004) the John J. Abel Award to the Outstanding American Pharmacologist under 40 from the American Society for Pharmacology and Experimental Therapeutics.
As a complement to his basic science focus on G-protein regulators, Dr. Siderovski also has both industrial and academic experience in high-throughput screening and small molecule discovery programs, beginning with a multi-year stint (1994 to 1998) at the AMGEN Institute of Toronto responsible for leveraging basic research discoveries into new drug discovery projects at Amgen Inc. headquarters in California. These early industrial efforts resulted in three issued patents:
1998 “Methods of Inhibiting Syp Binding to a CTLA-4 Receptor”; United States Patent 5,786,152. Marengere, Siderovski, & Mak.
2004 “Apoptosis-Inducing Factor”; United States Patent 6,773,911. Penninger, Kroemer, Siderovski, Zamzami, Susin, & Snow.
2008 “Apoptosis-Inducing Factor”; United States Patent 7,371,834. Penninger, Kroemer, Siderovski, Zamzami, Susin, & Snow.
Recent published works:
Giguère PM, Billard MJ, Laroche G, Buckley BK, Timoshchenko RG, McGinnis MW, Esserman D, Foreman O, Liu P, Siderovski DP, Tarrant TK. G-protein signaling modulator-3, a gene linked to autoimmune diseases, regulates monocyte function and its deficiency protects from inflammatory arthritis. Mol Immunol. 2013; 54(2):193-8.
Bosch DE, Siderovski DP. G protein signaling in the parasite Entamoeba histolytica. Exp Mol Med. 2013; 45:e15. doi: 10.1038/emm.2013.30.
Bosch DE, Kimple AJ, Manning AJ, Muller RE, Willard FS, Machius M, Rogers SL, Siderovski DP. Structural determinants of RGS-RhoGEF signaling critical to Entamoeba histolytica pathogenesis. Structure. 2013; 21(1):65-75.
Cohen SP, Buckley BK, Kosloff M, Garland AL, Bosch DE, Cheng J, Radhakrishna H, Brown MD, Willard FS, Arshavsky VY, Tarran R, Siderovski DP, Kimple AJ. Regulator Of G-Protein Signaling-21 (RGS21) is an inhibitor of bitter gustatory signaling found in lingual and airway epithelia. J Biol Chem. 2012 Oct 24.
Bosch DE, Willard FS, Ramanujam R, Kimple AJ, Willard MD, Naqvi NI, Siderovski DP. A P-loop mutation in Gα subunits prevents transition to the active state: implications for G-protein signaling in fungal pathogenesis. PLoS Pathog. 2012; 8(2):e1002553.
Kimple AJ, Bosch DE, Giguère PM, Siderovski DP. Regulators of G-protein signaling and their Gα substrates: promises and challenges in their use as drug discovery targets. Pharmacol Rev. 2011; 63(3):728-49.
Lambert NA, Johnston CA, Cappell SD, Kuravi S, Kimple AJ, Willard FS, Siderovski DP. Regulators of G-protein signaling accelerate GPCR signaling kinetics and govern sensitivity solely by accelerating GTPase activity. Proc Natl Acad Sci U S A. 2010; 107(15):7066-71.
Willard MD, Willard FS, Siderovski DP. The superfamily of ‘regulator of G-protein signaling’ (RGS) proteins. In: Bradshaw RA, Dennis EA, editors. Handbook of Cell Signaling. 2nd ed. San Diego (CA): Elsevier Press; 2009.