Dr. Ostrom’s lab seeks to understand how cells "pre-arrange"
multiple signaling components in GPCR signal transduction cascades.
His focus is on caveolae and lipid rafts as centers for such organization.
“Our long-term goal 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, Dr. Ostrom will examine signaling
mechanisms of G protein-coupled receptors. He is 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.
Dr. Ostrom seeks to elucidate the impact of compartmentation 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, he studies cardiac myocytes and fibroblasts, airway
smooth muscle cells and pulmonary fibroblasts.
In other
studies, Dr. Ostrom is accessing the release of nucleotides and activation
of P2Y receptors in various cultured cell lines. He has 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 appears to be due, in part, to membrane channel conductance.
The goal is to understand the physiological role of the autocrine/paracrine
signaling that is initiated by cellular release of ATP.
Recent Publications
Ostrom RS,
Naugle JE, Gregorian C, Hase M, Swaney JS, Insel PA, Brunton LL and
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, 2003.
Loomis WH,
Namiki S, Ostrom RS, Insel PA and Junger WG. Hypertonic stress co-stimulates
T cell IL-2 expression through a feedback mechanism involving ATP release
and P2 receptor activation of p38 MAP kinase. J Biol Chem 278(7):4590-6,
2003.
Insel PA
and Ostrom RS. Forskolin as a tool for examining adenylyl cyclase expression,
regulation and G protein signaling. Cell Mol Neurobiol 23(3):305-14,
2003.
Ostrom RS,
Rana BK and Insel PA. Stoichiometry of G Protein-coupled Receptor Signaling:
Implications in the Genomic Era. Pharmaceutical News, 2003.
Ostrom RS, Liu X, Head BP,
Gregorian C, Seasholtz TM and Insel PA. Localization of adenylyl cyclase
isoforms and G protein-coupled receptors in vascular smooth muscle cells:
expression in caveolin-rich and non-caveolin domains. Mol Pharmacol
62(4):983-92, 2002.
Ostrom RS.
New determinants of receptor-effector coupling: trafficking and compartmentation
in membrane microdomains. Mol Pharmacol 61(3):473-6, 2002.
For additional
information about Dr. Ostrom visit http://ostrom.utmem.edu/
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