Gregg Rokosh, PhD
Assistant Professor of Medicine
Tel.: (502) 852-2459
E-mail: Email Dr. Rokosh
Our lab studies the molecular, cellular, and physiologic function of three a1-adrenergic receptor (AR) subtypes present in the cardiovascular system. Activation of these subtypes by catecholamines protects, or preconditions, the heart from ischemia-induced damage and dysfunction, increases cardiac and smooth muscle contractility important for blood pressure regulation, and increases protein synthesis in vascular and cardiac muscle helping the cardiovascular system adapt to stress. Recently, we have created and used a1-AR subtype knockout mice to study differences in a1-AR subtype signaling. In these studies we have found that each subtype can activate distinct and different signaling pathways. The main focus in our lab is to determine how each a1-AR subtype couples to and activates distinct signaling pathways and whether the subtypes mediate distinct function. We use proteomic and molecular biology approaches to identify receptor domains that are important for interacting with signaling proteins that impart signaling specificity and to identify novel signaling proteins that might interact with one of the subtypes and can account for differences in signaling. a1-AR subtype-specific activation and signaling is correlated with preconditioning against myocardial stunning and infarct and blood pressure regulation using in vivo and in vitro mouse models. Changes in the global gene expression profile associated with the late phase of preconditioning are studied using DNA microarrays. This approach allows us to look for known genes that have not been associated with preconditioning and to identify novel unknown genes that may participate in this phenomenon. Our research focuses on all aspects of a1-AR receptor biology allowing us to understand the functional consequences of the distinct subtypes.
Selected Recent Publications:
Rokosh, D.G. and P. C. Simpson, Knockout of the a1A/C-adrenergic receptor subtype: the a 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure. 2002. Submitted
Rokosh, D.G., A. Nakamura, E. Foster, and P.C. Simpson, 2000, Gender related differences in survival and gene induction in a1A/C-adrenergic receptor knockout mice with pressure overload. Circulation 102:II-197.
Deng, D., D.G. Rokosh, and P.C. Simpson, 2000, Autonomous and growth factor-induced hypertrophy in cultured neonatal mouse cardiac mycoytes: comparison with rat. Circ. Res. 87:781-788.
Rokosh, D.G., A.F.R. Stewart, K.C. Chang, B.B. Bailey. J.S. Karliner, S.A. Camacho, C.S. Long, and P.C. Simpson, 1996, a 1-Adrenergic receptor subtype mRNAs are differentially regulated by a1-adrenergic and other hypertropic stimuli in cardiac myocytes in culture and in vivo: repression of a1B and a1D but induction of a1C, J. Biol. Chem. 271: 5839-5843.