Mark S. Taylor, Ph.D.
 Assistant Professor 

Ph.D., Basic Medical Sciences, Department of Physiology,
University of South Alabama.

Postdoctoral Studies: Department of Pharmacology,
University of Vermont College of Medicine.

Research Interests:

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.

Recent Publications:

Journal Articles  

1.      M. S. Taylor and J. N. Benoit. Effects of IBMX on norepinephrine-induced vasoconstriction in small mesenteric arteries. Am. J. Physiol. 276(4pt1): G909-14, 1999.

2.      M. S. Taylor and J. N. Benoit. Effect of milrinone on small mesenteric artery vasoconstriction; role of K⁺ channels. Am. J. Physiol. 277(1pt1): G69-78, 1999.

3.      W. G. Dostmann, M. S. Taylor, C. K. Nickl, J. E. Brayden, R. Frank and W. Tegge. Highly specific, membrane-permeant peptide blockers of cGMP-dependent protein kinase Ia inhibit NO-induced cerebral dilation. Proc. Natl. Acad. Sci. U S A. 97(26): 14772-7, 2000.

4.      W. G. Dostmann, W. Tegge, R. Frank, C. K. Nickl, M. S. Taylor and J. E. Brayden. Exploring the mechanisms of vascular smooth muscle tone with highly specific, membrane permeable inhibitors of cyclic GMP-dependent protein kinase Iα. Pharmacology and Therapeutics. 93:203-215, 2002.

5.      M. S. Taylor, A. D. Bonev, T. P. Gross, D. M. Eckman, J. E. Brayden, C. T. Bond, J. P. Adelman and M. T. Nelson. Altered expression of small-conductance Ca²⁺-activated K⁺ (SK3) channels modulates arterial tone and blood pressure. Circ Res. 93(2):124-31, 2003.

6. M. S. Taylor, C. Okwuchukwuasanya, C. K. Nickl, J. E. Brayden and W. G.   Dostmann. Inhibition of cGMP-dependent protein kinase by the cell-permeable peptide DT-2 reveals a novel mechanism of vasoregulation. (submitted)
7. M. S. Taylor, A. D. Bonev and M. T. Nelson. Dynamic Ca²⁺ signaling in vascular endothelium: Role of small conductance, Ca²⁺-activated K⁺ (SK3) channels. (in preparation)
8. M. S. Taylor. Modulation of arterial tone by small and intermediate conductance Ca²⁺-activated K⁺ channels under physiological conditions of pressure and flow. (in preparation)

Reviews

1.      J. N. Benoit, H. Gao, and M. S. Taylor. Vascular reactivity following ischemia/reperfusion. Frontiers in Bioscience. 2: e28-e33, 1997.

2.      M. S. Taylor, A. M. McMahon, J. D. Gardner and J. N. Banoit. Cyclic nucleotides and vasoconstrictor function: physiological and pathophysiological considerations. Pathophysiology. 5: 233-245, 1999.

3.   M. S. Taylor, A. D. Bonev and M. T. Nelson. Vasoregulatory role of    endothelial   Ca²⁺-activated K⁺ channels. (in preparation)