Research Interests
We are primarily focused on the vascular smooth muscle cell (SMC) which forms the muscular layers of the heart vessel wall and regulates contraction and tone. The SMC also plays a critical role in the pathogenesis of atherosclerosis. In atherosclerosis, healthy/contractile SMCs can undergo phenotype modulation, showing high rates of proliferation and migration which, in cooperation with several other cell types, leads to blood vessel narrowing and stenosis. Luminal narrowing can compromise blood flow to the heart, for example, leading to myocardial ischemia or a heart attack. Revascularization of the atherosclerotic blood vessel is accomplished clinically by balloon angioplasty and deployment of a wire mesh stent to restore blood flow. A major potential adverse effect of stenting is acute injury to the vessel which can lead to in-stent restenosis; a new lesion that is rich in SMCs. Thus, the primary focus of our research is to determine mechanisms that regulate smooth muscle cell (SMC) phenotypic modulation in response to atherosclerotic stimuli and acute vascular injury.
We employ the use of several highly innovative techniques: laser capture microdissection, mouse Cre/lox technology for in vivo gene mutagenesis, novel in vivo vascular injury and atherosclerosis models, biomedical models/devices that mimic the artery in vitro, derivation of SMCs from adult and embryonic stem cells, and novel pharmacological reagents to target SMC phenotypic modulation, as well as classic molecular biology techniques and classic vascular physiology techniques. This integrated approach to understanding vascular SMC phenotypic modulation allows us to fully understand the disease process from the DNA level in vitro to the whole animal level in vivo with a strong emphasis of translating our finding to real human translational events.
We are currently focused intensely on 3 mechanisms that regulate SMC phenotypic modulation: Calcium (Ca), Sphingosine-1-phosphate (S1P, and Endothelial cells (EC).
Selected Publications
1. Owens GK, Kumar MS and Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. [Invited Review] Physiol Rev 84: 767-801, 2004.
2. Wamhoff BR, Bowles DK, Owens, GK. Excitation-transcription coupling (ETC) [Invited Review]. Circ Res, 98(7):868-78, 2006.
3. Wamhoff BR*, Sinha S*, Neppl R, Helmke B, McCanna ME, Somlyo AV, Owens GK. Derivation of a pure population of functional smooth muscle cells from genetically engineered embryonic stem cells. Stem Cells. Jul;24(7):1678-88, 2006.
4. Wamhoff BR and Owens GK. Conditional Mouse Models of Muscle Differentiation and Disease. In, Handbook of Experimental Pharmacology (HEP): Conditional Mutagenesis: An Approach to Disease Models, 2006 (In Press).
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