Alan Victor Smrcka, Ph.D.

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Contact

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 711
Rochester, New York 14642

Office: 585 275-0892 (primary)

Lab: 585 275-0859

Fax: 585 273-2652

Portrait

G protein coupled receptors (GPCRs) form a large family of cell surface receptors responsible for triggering cellular responses to a variety of extracellular stimuli including drugs such as opiates, and hormones such as adrenaline, serotonin or acetylcholine. All GPCRs function through activation of trimeric G proteins located on the inner surface of the plasma membrane. Activated G proteins target ion channels or enzymes that produce second messengers with a variety of effects depending on the type of cell that is stimulated. Examples include regulation of synaptic transmission in the central nervous system, chemotaxis in the immune system, and vascular remodeling in the cardiovascular system. This family of receptors is an important target for pharmaceuticals and defects in GPCR systems are responsible for a number of diseases.

Our laboratory focuses on analysis of the interactions between the G proteins and their protein targets at a molecular and structural level with the goal of understanding how these interactions lead to alterations in protein and cellular activities. Another goal is to connect the biochemical information about protein interaction interfaces to specific cellular physiologies. To this end we are developing antagonists of specific G protein interactions and using these tools to probe the functions of those interactions in living cells. This approach will help to define the roles of specific G protein interactions in physiological processes and as potential targets for therapeutic intervention in cardiovascular disease or cancer.

Current Appointments

Education
PhD Biochemistry University of Arizona 1990
MS Botany Arizona State University 1984
BS Biology University of Connecticut 1981
Post-Doctoral Training & Residency
Postdoctoral Fellow, Pharmacology Department, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, laboratory of Dr. Paul C. Sternweis 1990 - 1994
Fellowship Awards
National Institutes of Health Postdoctoral Research Fellowship NRSA: Regulation of Phospholipase C by G Proteins 1991 - 1993

Lab Website

http://www.urmc.rochester.edu/phph/projects/smrcka/index.htm


Recent Journal Articles
Showing the 5 most recent journal articles. (64 available)
Oestreich EA; Malik S; Goonasekera SA; Blaxall BC; Kelley GG; Dirksen RT; Smrcka AV. "Epac and Phospholipase C{epsilon} Regulate Ca2+ Release in the Heart by Activation of Protein Kinase C{epsilon} and Calcium-Calmodulin Kinase II." The Journal of biological chemistry. 2009; 284(3):1514-22. Epub 2008 Oct 27.
Lehmann DM; Seneviratne AM; Smrcka AV. "Small molecule disruption of G protein beta gamma subunit signaling inhibits neutrophil chemotaxis and inflammation." Molecular pharmacology. 2008; 73(2):410-8. Epub 2007 Nov 15.
Smrcka AV. "G protein betagamma subunits: central mediators of G protein-coupled receptor signaling." Cellular and molecular life sciences : CMLS. 2008; 65(14):2191-214.
Smrcka AV; Lehmann DM; Dessal AL. "G protein betagamma subunits as targets for small molecule therapeutic development." Combinatorial chemistry & high throughput screening. 2008; 11(5):382-95.
Mathews JL; Smrcka AV; Bidlack JM. "A novel Gbetagamma-subunit inhibitor selectively modulates mu-opioid-dependent antinociception and attenuates acute morphine-induced antinociceptive tolerance and dependence." The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008; 28(47):12183-9.