Department of Physiology,
University of South Alabama
College of Medicine
Mobile, AL 36688
Ph.D., Basic Medical Sciences, Department of Physiology, University of South Alabama.
Postdoctoral Studies: Department of Pharmacology, University of Vermont College of Medicine.
Dynamic regulation of arterial tone influences blood pressure and flow, and ultimately plays a critical role in cardiovascular health and disease. My research focuses primarily on cellular signaling pathways that impair excitation-contraction coupling in vascular smooth muscle (VSM), thereby reducing contractility and promoting vasodilation. In particular, I am interested in mechanisms that provide constant or tonic modulation of vascular tone by controlling membrane potential, intracellular Ca2+ and the sensitivity of the contractile apparatus to Ca2+. My projects have investigated mechanisms of cyclic nucleotide vasorelaxation, including the pivotal roles of phosphodiesterases and cyclic nucleotide dependent protein kinases. Recent studies using a novel class of cGMP-dependent protein kinase (PKG) inhibitors suggest a critical vasoregulatory role for constitutively active PKG in VSM.
The vascular endothelium (a single layer of cells lining the lumen of the entire vasculature) constantly modulates vascular tone. I am currently studying the communication between the endothelium and smooth muscle, specifically the role of certain ion channels that influence this communication and alter vascular reactivity. Of particular interest are certain small and intermediate conductance Ca2+-activated K+ channels (SK3 and IK, respectively) that elicit membrane potential hyperpolarization in endothelial cells. These channels may exert fundamental regulation of vascular reactivity through tight control of endothelial function. We recently showed that SK3-dependent hyperpolarization is communicated to adjacent smooth muscle, promoting vasodilation, and that the magnitude of this effect is dependent on the level of SK3 expression. Expression levels of these channels may change considerably with hormonal status (i.e. with pregnancy) and pathological states, profoundly influencing cardiovascular function. Most recently, high-speed confocal imaging of arterial preparations has revealed dynamic and complex modes of Ca2+ signaling in the intact endothelium, opening exciting new areas for exploration. Future studies will investigate key factors modulating vascular tone and reactivity, including dynamic protein (i.e. SK3) expression, control of endothelial cell membrane potential and Ca2+, and mechanisms of communication between the endothelium and smooth muscle in health and disease. I employ various techniques and methodologies including arterial myography, confocal Ca2+ imaging, electrophysiology, molecular biology, immunohistochemistry, cell/tissue culture, and the use of genetic constructs.
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