Jefferson C. Frisbee, Ph.D.
	Professor of Physiology and Pharmacology Graduate Training: University of Guelph Fellowship: University of Washington & Medical College of Wisconsin
	Office: 3002-HSN Lab: 3145-HSN PO Box 9105 Morgantown, WV 26506	Email: jfrisbee@hsc.wvu.edu Phone: 304-293-6527 Fax: 304-293-5513

Research Interests:

A developing characteristic of the metabolic syndrome, defined as the combined presentation of obesity, insulin resistance/type II diabetes mellitus, dyslipidemia and hypertension, is a progressive inability to match blood flow to working tissues with metabolic demand arising from those tissues, such that an evolving ischemic condition develops. While this syndrome presently afflicts more than 47 million Americans (American Heart Association), defining specific causes underlying this perfusion/demand mismatch has been challenging, as previous studies in human subjects have determined that alterations to vascular reactivity, a progressive structural narrowing of individual vessels, and a developing reduction in the density of microvessels within skeletal muscle can all occur during the metabolic syndrome in afflicted individuals. Each of these conditions has the potential to elevate vascular resistance and compromise the ability of skeletal muscle to resist fatigue through impairments in the processes of mass transport and exchange.

Our research program is targeted at understanding alterations to microvascular structure and function during the development of the metabolic syndrome. While individual projects examine alterations to microvascular reactivity to physiological and pharmacological stimuli, additional efforts are directed at understanding modifications to microvascular structure (at both the individual vessel and whole network levels of resolution) which develop with the metabolic syndrome. However, the underlying purpose of these projects is the integrative understanding of how alterations to both structure and function of the microcirculation combine to impact perfusion to the individual organ or tissue in question in animals afflicted with the full metabolic syndrome or with individual components of it.

While the predominant research thrust of the laboratory employs the Zucker rat model of the metabolic syndrome (one brought on by hyperphagia), other avenues of investigation are employing models of the constituent elements of the metabolic syndrome (i.e., hypertension, insulin resistance, dyslipidemia). Further, while much of our previous investigation has focused on alterations to microvascular structure/function and perfusion within the skeletal muscle circulation, evolving projects focus on the interactions between clinical depressive symptoms and peripheral vascular disease as well as the evolution of the aspirin resistant condition in hyperlipidemia. 

Selected Publications:

1. Depressive behavior and vascular dysfunction: a link between clinical depression and vascular disease? d'Audiffret AC, Frisbee SJ, Stapleton PA, Goodwill AG, Isingrini E, Frisbee JC. J Appl Physiol. 2010 Feb 18. PMID: 20167667: PubMed Article
   
2. Inactivation of L-type Calcium Channel Modulated by HCN2 Channel. Lin YC, Huang J, Zhang Q, Hollander JM, Frisbee JC, Martin KH, Nestor C, Goodman RL, Yu HG. Am J Physiol Cell Physiol. 2010 Feb 17. PMID: 20164379: PubMed Article
3. Differential impact of familial hypercholesterolemia and combined hyperlipidemia on vascular wall and network remodeling in mice. Stapleton PA, Goodwill AG, James ME, D'Audiffret AC, Frisbee JC. Microcirculation. 2010 Jan;17(1):47-58.PMID: 20141600: PubMed Article
4. Impact of chronic anticholesterol therapy on development of microvascular rarefaction in the metabolic syndrome. Goodwill AG, Frisbee SJ, Stapleton PA, James ME, Frisbee JC. Microcirculation. 2009 Nov;16(8):667-84.PMID: 19905967: PubMed Article
5. In vivo vascular wall tissue characterization using a strain tensor measuring (STM) technique for flow-mediated vasodilation analyses. Mahmoud AM, Frisbee JC, D'Audiffret A, Mukdadi OM. Phys Med Biol. 2009 Oct 21;54(20):6217-38. PMID: 19794242: PubMed Article
6. Rescue of a trafficking defective human pacemaker channel via a novel mechanism: roles of Src, Fyn, and Yes tyrosine kinases. Lin YC, Huang J, Kan H, Frisbee JC, Yu HG. J Biol Chem. 2009 Oct 30;284(44):30433-40. PMID: 19748888: PubMed Article
7. Growth-dependent changes in the contribution of carbon monoxide to arteriolar function. Samora JB, Goodwill AG, Frisbee JC, Boegehold MA. J Vasc Res. 2010;47(1):23-34. PMID: 19672105: PubMed Article
8. Impact of Chronic Anticholesterol Therapy on Development of Microvascular Rarefaction in the Metabolic Syndrome. Goodwill AG, Frisbee SJ, Stapleton PA, James ME, Frisbee JC. Microcirculation. 2009 Aug 4:1-18. PMID: 19905967: PubMed Article
9. Integration of skeletal muscle resistance arteriolar reactivity for perfusion responses in the metabolic syndrome.
   Frisbee JC, Hollander JM, Brock RW, Yu HG, Boegehold MA. Am J Physiol Regul Integr Comp Physiol. 2009 Jun;296(6):R1771-82. PMID: 19386988: PubMed Article
10. Goodwill AG, Stapleton PA, James ME, d'Audiffret AC, Frisbee JC. Increased arachidonic acid-induced thromboxane generation impairs skeletal muscle arteriolar dilation with genetic dyslipidemia. Microcirculation. 2008 PMID: 1870229: PubMed Article
11. Goodwill AG, James ME, Frisbee JC. Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension. Am J Physiol Heart Circ Physiol. 2008 PMID: 186689495: PubMed Article
12. Peterson JM, Bryner RW, Frisbee JC, Alway SE. Effects of Exercise and Obesity on UCP3 Content in Rat Hindlimb Muscles. Med Sci Sports Exerc. 2008 PMID: 1865530: PubMed Article
13. Stapleton PA, James ME, Goodwill AG, Frisbee JC. Obesity and vascular dysfunction. Pathophysiology. 2008, 15(2):79-89. PMID:18571908: PubMed Article
14. Samora JB, Frisbee JC, Boegehold MA. Hydrogen peroxide emerges as a regulator of tone in skeletal muscle arterioles during juvenile growth. Microcirculation. 2008;15(2):151-61.PMID: 18260005: PubMed Article
15. Stapleton PA, Goodwill AG, James ME, Frisbee JC. Altered mechanisms of endothelium-dependent dilation in skeletal muscle arterioles with genetic hypercholesterolemia. Am J Physiol Regul Integr Comp Physiol. 2007;293(3):R1110-9.PMID: 176261220: PubMed Article
16. Frisbee JC. Obesity, insulin resistance, and microvessel density. Microcirculation. 2007;14(4-5):289-98. PMID: 1857/1908 (PubMed - as supplied by publisher) PubMed Article
17. Frisbee JC, Samora JB, Basile DP. Angiostatin does not contribute to skeletal muscle microvascular rarefaction with lonitric oxide bioavailability. Microcirculation. 2007;114(2):145-53. PMID: 17365669 PubMed Article

Lab Personnel: Alexandre C. d'Audiffret, MD - Vascular Surgeon Milinda James - Research Assistant II Joshua Butcher, Graduate Student Adam Goodwill - Ph.D. Graduate Student
	Front: Phoebe Stapleton, Milinda James Back: Alexandre d'Audiffret, M.D., Jefferson Frisbee, Ph.D., Adam Goodwill