Robert Gros
Assistant Professor
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PH.D. The University of Western Ontario |
The focus of my laboratory is to investigate the cellular and molecular mechanisms involved in the regulation of vascular function. In particular, we are interested in the role and regulation of G-protein-coupled receptor signaling pathways in both vascular smooth muscle cell and endothelial cell function under physiological and pathological conditions (i.e. hypertension and diabetes). The regulation of vascular tone is complex and involves many different signaling pathways, including the large family of G-protein-coupled receptors (GPCRs), which play a crucial role in regulating overall vascular function. In hypertension, GPCR-mediated vasodilation is impaired, a finding observed in both human hypertensive subjects as well as animal models of hypertension. We and others have demonstrated that this impairment in GPCR-mediated vasodilation is in part due to increased expression and/or function of G-protein-coupled receptor kinases (a large family of kinases that phosphorylate GPCRs). However, the cellular/molecular mechanism(s) involved in the regulation of altered GRK expression during the hypertensive state (or other pathological conditions) in unknown and is the focus of my laboratory's research effort. To dissect the role and regulation of these signaling pathways, a range of biochemical, cellular and molecular techniques as well as integrative approaches (such as adenoviral-mediated gene-transfer into isolated blood vessels) are utilized. Key Research Issues:
-Examine the regulation of G-protein-coupled receptor kinases in cardiovascular disease.
-Identification of novel regulators of vascular G-protein-coupled receptor signaling pathways under physiological and patho-physiological conditions
Gros, R, Ding, QM#, Chorazcyzewski, J., Pickering, JG., Limbird, L. and Feldman, RD. Adenylyl cyclase isoform-selective regulation of vascular smooth muscle proliferation and cytoskeletal re-organization. Circulation Research, 2006;99(8):845-52.Epub 2006 Sept 14. #Authors contributed equally to manuscript. Gros, R, Ding, QM.#, Armstrong, S., O'Neil, C., Pickering, JG. and Feldman, RD. Rapid Effects of Aldosterone on Clonal Human Smooth Muscle Cells. American Journal of Physiology: Cell Physiology, 2007; 292(2):C788-94. Epub 2006 Sep 13.. #Authors contributed equally to manuscript. Choi, J., Chiang, A., Taulier, N., Gros, R., Parini, A. and Husain, M. A calmodulin binding site on cyclin-E mediates Ca2+-sensitive G1/S transition in vascular smooth muscle cells. Circulation Research 2006; 98:1273-1281. Epub 2006 Apr 20 Gros, R., Ding, QM., Chorazcyzewski, J., Andrews, J., Pickering, JG., Hegele, RA. and Feldman, RD. The impact of blunted beta-adrenergic responsiveness on growth regulatory pathways in hypertension. Molecular Pharmacology. 2006; 69(1):317-327. Toporsian, M., Gros, R., Kabir, MG, Vera, S., Govindaraju, K., Eidelman, DH., Husain, M. and Letarte, M. Endoglin modulates the eNOS activation complex in the pathogenesis of HHT1. Circulation Research 2005; 96(6):684-692. Epub 2005 Feb 17 Gros, R., Afroze, T., You, XM., Kabir, G., Van Wert, R., Kalair, W., Hoque, AE, Mungrue, IN. and Husain, M. Plasma Membrane Calcium ATPase Over-expression in Arterial Smooth Muscle Increases Vasomotor Responses and Blood Pressure. Circulation Research. 2003; 93:614-621. Gros, R, Van Wert, R, You, X., Thorin, E. and Husain, M. Effects of age, gender, and blood pressure on myogenic responses of mesenteric arteries from C57BL/6 mice. American Journal of Physiology- Heart & circulation. 2002; 282(1): H380-H388. Gros, R, Chorazyczewski, J., Meek MD, Benovic, JL, Ferguson, SSG and Feldman, RD. G-protein-coupled receptor kinase activity in hypertension: Increased vascular and lymphocyte GRK-2 protein expression. Hypertension. 2000; 35:38-42.
