Gary K. Owens, Ph.D.
Professor
| E-mail Address: |
gko@virginia.edu |
|---|---|
| Telephone: | Office: 434-924-2652 Lab: 434-924-5993 |
| Address: | Molecular Physiology and Biological Physics University of Virginia PO Box 800736 Charlottesville, VA 22908-0736 |
Research Summary
The major long-term goal of research in this laboratory is to elucidate cellular and molecular mechanisms that control growth and differentiation of vascular smooth muscle cells (SMC) during development of the cardiovascular system, and to identify mechanisms that contribute to alterations in the differentiated state of the SMC that contribute to development of vascular diseases such as hypertension or atherosclerosis. Areas of current emphasis include: 1) examination of the molecular mechanisms whereby contractile agonists such as angiotensin II stimulate hypertrophy of vascular smooth muscle; and 2) examination of factors that regulate growth of smooth muscle following vascular injury as occurs with angioplasty surgery. The former studies are currently focusing on identification of kinase/phosphatase signaling pathways that regulate phosphorylation and activity of the ribosomal RNA gene transcription factor upstream binding factor (UBF). The latter studies are investigating signaling pathways whereby thrombin stimulates SMC growth, and exploring ways to inhibit post-angioplasty restenosis in animal models by introduction of a gene encoding the potent anti-thrombotic protein hirudin at the site of vascular injury.
Studies of SMC differentiation are aimed at determining molecular mechanisms that control the coordinate expression of genes characteristic of differentiated SMC, as well as identification of local environmental factors/cues that influence the differentiation process. This includes exploration of the influence of growth factors, extracellular matrix, mechanical forces, and cell-cell interactions on expression of smooth muscle cell specific contractile proteins at both the translational and transcriptional levels, and examination of transcriptional regulation of smooth muscle specific contractile protein genes. One approach has been to clone genes characteristic of differentiated SMC including smooth muscle a-actin and smooth muscle myosin heavy chain, and to identify regulatory elements and transcription factors that control expression of these genes using a combination of cell culture, transgenic, and gene knockout systems.
Representative Publications:
Hershey JC, Hautmann M, Thompson MM, Rothblum LI, Haystead TAJ, Owens GK: Angiotensin II-induced hypertrophy of rat vascular smooth muscle is associated with increased 18S rRNA systhesis and phosphorylation of the rRNA transcription factor, upstream binding factor. J Biol Chem 1995;270:25096-25101 [View Entrez Listing]
Owens, G.K. Regulation of differentiation of vascular smooth muscle cells.[Review]. Physiol Rev 1995;75(3):487-517. [View Entrez Listing]
Madsen CS, Hershey JC, Hautmann MB, White SL, Owens GK: Expression of the smooth muscle myosin heavy chain gene is regulated by a negative-acting GC-rich element located between two positive-acting serum response factor-binding elements. J Biol Chem 1997;272:6332-6340 [View Entrez Listing]
Hautmann MB, Thompson MM, Swartz EA, Olson EN, Owens GK: Angiotensin II-induced stimulation of smooth muscle alpha-actin expression by serum response factor and the homeodomain transcription factor MHox. Circ Res 1997 81:600-610