Room 252 Nash Annex
(901) 448-1181
Fax (901) 448-7300

rostrom@utmem.edu

Webpage: Web Page

B.A. Biology, Dartmouth College, 1990
Ph.D. Pharmacology and Toxicology, University of California,Irvine, 1998

Research Interest:

We are seeking to understand how cells "pre-arrange" multiple signaling components in GPCR signal transduction cascades and are focused on caveolae and lipid rafts as centers for such organization. Our long-term focus is to understand how such compartmentation impacts cellular response in a physiological setting.
Using molecular cloning, expression of cloned signaling proteins, and a variety of cell biological and biochemical approaches, we examine signaling mechanisms of G protein-coupled receptors. We are interested in the organization of signaling microdomains in the plasma membrane, especially in lipid raft/caveolin-rich regions, in which various receptors, G-proteins and effectors, particularly certain isoforms of adenylyl cyclase, localize. We seek to understand how such compartmentation impacts on cellular responses with the goal of developing novel gene therapy strategies to modulate cellular responses through changes in expression of limiting components in the signaling pathways. Adenylyl cyclase is one such limiting component. Currently, we study cardiac myocytes and fibroblasts, airway smooth muscle cells and pulmonary fibroblasts.
In other studies, we assess release of nucleotides and activation of P2Y receptors in various cultured cell lines. We have found that virtually all cells are capable of releasing ATP in response to mild mechanical stimuli or other forces that cause membrane deformation. The mechanism of this release is not clear, but it appears to be due, in part, to membrane channel conductance. Our goal is to understand the physiological role of the autocrine/paracrine signaling that is initiated by cellular release of ATP.

Selected Publications:

Ostrom RS, Violin JD, Coleman S, Insel PA. Selective enhancement of ß-adrenergic receptor signaling by overexpression of adenylyl cyclase type 6: co-localization of receptor and adenylyl cyclase in caveolae of cardiac myocytes. Mol Pharmacol , 57:1075-1079, 2000. PubMed
Ostrom RS, Gregorian C, Insel PA. Cellular release of and response to ATP as key determinants of the set-point of signal transduction pathways J Biol Chem , 275:11735-11739, 2000. PubMed
Ostrom RS, Gregorian C, Drenan RM, Gabot K, Rana BK, Insel PA. Key role for constitutive cyclooxygenase-2 of MDCK cells in basal signaling and response to released ATP, Am J Physiol: Cell Physiol , 281:C524-C531, 2001. PubMed
Ostrom RS, Gregorian C, Drenan RM, Xiang Y, Regan JW, Insel PA. Receptor number and caveolar co-localization determine receptor coupling efficiency to adenylyl cyclase, J Biol Chem , 276(45):42063-9, 2001 PubMed
Zheng B, Ma Y-C, Ostrom RS, Lavoie C, Gill GN, Insel PA, Huang X-Y, Farquhar MG. RGS-PX1: A gap for G(s and a sorting nexin in vesicular trafficking, Science , 294:1939-1942, 2001. PubMed
Ostrom RS, Liu X, Gregorian C, Drenan RM, Seasholtz TM, Insel PA. Localization of adenylyl cyclase isoforms and G protein-coupled receptors in vascular smooth muscle cells: expression in caveolin-rich and noncaveolin domains , Mol Pharmacol , 62:983-992, 2002. PubMed
Loomis WH, Namiki S, Ostrom RS, Insel PA, Junger WG. Hypertonic Stress Increases T Cell Interleukin-2 Expression through a Mechanism That Involves ATP Release, P2 Receptor, and p38 MAPK Activation, J Biol Chem , 278(7):4590-6, 2003. PubMed
Ostrom RS, Naugle JE, Hase M, Gregorian C, Swaney JS, Insel PA, Brunton LL, Meszaros JG. Angiotensin II Enhances Adenylyl Cyclase Signaling via Ca2+/Calmodulin: Gq-Gs CROSS-TALK REGULATES COLLAGEN PRODUCTION IN CARDIAC FIBROBLASTS. J. Biol.Chem. 278(27): 24461-8, Jul 2002. PubMed

Ostrom RS and Insel PA. Caveolar microdomains of the sarcolemma: compartmentation of signaling molecules comes of age. Circ Res , 84(9):1110-2 , 1999. PubMed
Post SR, Ostrom RS and Insel PA. Biochemical methods for detection and measurement of cyclic AMP and adenylyl cyclase activity . Methods Mol Bio , 126:363-74 , 2000. PubMed
Ostrom RS, Post SR and Insel PA. Stoichiometry and compartmentation in G protein-coupled receptor signaling: implications for therapeutic interventions involving Gs. J Pharmacol Exp Ther , 294(2):407-412, 2000. PubMed
Ostrom RS. New determinants of receptor-effector coupling: trafficking and compartmentation in membrane microdomains. Mol Pharmacol , 61(3):473-6, 2002. PubMed
Insel PA, Ostrom RS, Zambon AC, Hughes RJ, Balboa MA, Shehnaz D, Gregorian C, Torres B, Firestein BL, Xing M, Post SR. P2Y receptors of MDCK cells: epithelial cell regulation by extracellular nucleotides. Clin Exp Pharmacol Physiol , 28(4):351-4 , 2001. PubMed