University of Virginia Health System

Dr. Gary K. Owens
Molecular Regulation of Smooth Muscle Growth and Differentiation 

Regulation of Smooth Muscle Cell Differentiation during Vascular Development and in Disease
A major focus of studies in our laboratory is to understand molecular mechanisms that regulate the growth and differentiation of vascular smooth muscle cells during vascular development and in vascular diseases such as atherosclerosis that are characterized by alterations in the control of smooth muscle differentiation. Current studies are aimed at identifying molecular mechanisms that control the coordinate expression of contractile protein genes such as smooth muscle *-actin and smooth muscle myosin heavy chains that are required for the differentiated function of the smooth muscle cell. Studies involve use of a wide repertoire of molecular genetic techniques and include identification of cis elements and trans regulatory factors that regulate cell-type specific expression of smooth muscle differentiation genes both in cultured cell systems and in vivo in transgenic mice.

We use a variety of gene knockout, chimera, and gene over-expression approaches to investigate the role of specific transcription factors and local environmental cues (e.g. growth factors, mechanical factors, cell-cell and cell-matrix interactions, etc.) in regulation of smooth muscle differentiation during vascular development, or in cardiovascular disease. A particularly exciting recent development is that we have employed smooth muscle specific promoters originally cloned and characterized in our laboratory (see references 3 & 4) to create mice in which we can target knockout (or over-expression) of genes of interest specifically to smooth muscle cells (see reference 5). Such systems will permit development of unique and powerful genetic mouse model systems with which to directly explore mechanisms that contribute to vascular development, and remodeling in vivo, as well as to investigate the etiology of a variety of major cardiovascular diseases including hypertension and atherosclerosis. In addition, we have employed these promoters to develop methods for producing purified populations of smooth muscle cells or smooth muscle cell progenitor cells from both embryonic and somatic stem cells. The latter studies have tremendous potential for use in either correcting gene defects that contribute to cardiovascular disease, or alternatively delivering therapeutic genes to treat or possibly cure these diseases.