Research Interest:Regulation of Smooth Muscle Cell Differentiation during Vascular Development and in DiseaseA 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 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. In addition, we use a variety of gene knockout, and chimera analyses in genetically modified mice to investigate the role of soluable factors such as PDGF, TGFß1 and angiotensin II in regulation of smooth muscle differentiation during vascular development, injury, and atherogenesis. Finally, we have employed various embryonic and adult stem cell systems developed in our laboratory to investigate mechanisms that control early stages of lineage determination in smooth muscle cells, and to investigate possible uses of stem cell derived smooth muscle cells for various gene therapy and tissue engineering applications for treating cardiovascular disease. Representative Publications: 1. Owens GK. Regulation of differentiation of vascular smooth muscle cells. [Review]. Physiol Rev 1995;75:487-517. 2. 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. [http://circres.ahajournals.org/cgi/content/full/81/4/600] 3. Madsen,C.S.; Regan,C.P.; Hungerford,J.E.; White,S.L.; Manabe,I.; Owens,G.K. Smooth muscle-specific expression of the smooth muscle myosin heavy chain gene in transgenic mice requires 5"-flanking and first intronic DNA sequence. Circ. Res. 1998; 82: 908-917. [http://circres.ahajournals.org/cgi/content/full/82/8/908] 4. Mack, C.P. and G.K. Owens. Regulation of SM alpha-actin expression in vivo is dependent upon CArG elements within the 5' and first intron promoter regions. Circ.Res. 84: 852-861, 1999. [http://circres.ahajournals.org/cgi/reprint/84/7/852]. 5. Adam PJ, Regan CP, Hautmann MB, GK Owens. A negatively actin krupple-like transcription factor binds a transforming growth factor beta control element required for expression of the smooth muscle cell differentiation mark SM22a in vivo. Journal of Biological Chemistry 2000;275 (48) 37798-37806. [http://www.jbc.org/cgi/content/full/275/48/37798] 6. Manabe I., and GK Owens.
Recruitment of SRF and hyperacetylation of histones at smooth muscle-specific
regulatory regions during differentiation of a novel P19-derived in
vitro smooth muscle differentiation system. Cir. Res. 2001;88:1127-1134.
http://circres.ahajournals.org/cgi/reprint/88/11/1127.pdf  |
