Department of Pharmacology Faculty
Rennolds Ostrom, Ph.D.
- B.A. Biology, Dartmouth College, 1990
- Ph.D. Pharmacology and Toxicology, University of California, Irvine, 1998
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.