Dr. Christopher J. Wingard, M.S., Ph.D.
| ||Associate Professor |
Department of Physiology
Phone: (252) 744-2804
Fax: (252) 744-3460
Brody School of Medicine
Department of Physiology, 6W-39
600 Moye Blvd.
Greenville, NC 27834
The theme of our laboratory is to understand the regulation of smooth muscle contraction and relaxation. In particular, we focus on elucidating mechanisms responsible for unique contractile responses of smooth muscle in several vasculatures. Because regulation of blood flow into a variety of organs is essential for their normal function the major projects of the lab, as outlined below, include efforts to understand the physiologic control of vascular tone, molecular determinates of vascular and non-vascular smooth muscle function, as well as the effects of cardiovascular risk factors on vascular function.
The fundamental hypothesis based on the central theme outlined above is that detriments in vascular function are explained by variations in the signaling elements of smooth muscle comprising the target organs. Vascular smooth muscle is distinct from other smooth muscle types and thus, may express a unique complement of receptors and signaling pathways. To address this, we are examining some of the known pharmacologic behaviors of the smooth muscle in the light of new techniques in molecular biology and animal models of vascular dysfunction. Specifically, we are using the variations in vasoconstrictor/vasodilator sensitivity to determine if there are correlative changes in receptor expression or the associated signaling pathways. We have 3 major projects on going in the lab are described below.
Airborne particulate matter and the negative impact on vascular reactivity and cardiovascular health:
Recent observations indicate that pulmonary inflammation induced by airborne particulate matter leads to activation of circulating neutrophils and the coronary endothelium, which enhances myocardial inflammation following ischemia reperfusion. Our data indicates that this effect is associated with endothelial modulation of aortic vascular smooth muscle reactivity in a manner consistent with a defect in adenosine control of endothelial-dependent relaxation. The specific hypothesis of this project is that neutrophilic inflammation induced by acute exposure to PM activates the endothelium, leading to an imbalance in signaling through adenosine A1, A2, and A3 receptors. Subsequent inhibition of A2 receptors by A1 and A3 receptor signaling, reduces endothelial-dependent relaxation of vascular smooth muscle, predisposing the myocardium to infarction; and altered adenosine signaling increases the severity of myocardial inflammation subsequent to reperfusion. We use a mouse model for studies of endothelium-smooth muscle interactions and to define the effects of PM exposure on cellular, protein, and molecular targets in the myocardium during ischemia-reperfusion injury, as well as affects on coronary and pulmonary vasculature, myocardial function, and effects of specific adenosine receptor antagonists. This work will provide definitive mechanistic evidence of the link between airborne particulate and cardiovascular disease.
Impact of RhoA/Rho-kinase signaling on penile smooth muscle function and erection:
Our primary goal in understanding the physiologic regulation of penile circulation is examining the role of elements of the Ca2+-sensitization process on maintaining smooth muscle contraction. Traditionally erection, more specifically erectile dysfunction, has focused on the inability to relax the smooth muscle of penile vasculature by means of nitric oxide production. However, the population of men effectively treated by agents which prolong the effect of NO (e.g. Viagra, Lavitra or Cilais) has not resolved all the dysfunction. An emerging concept is the role signaling pathways like the RhoA/Rho-kinase have on augmenting the contractile sensitivity of the penile smooth muscle. Currently we are exploring interactions between various vasoconstrictors (phenylephrine and endothelin-1) with downstream signaling molecules (RhoA/ROCK/RND and PKC) that mediate a sensitizing effect on smooth muscle contractile tone. These studies include analysis of penile vascular hemodynamics, in situ measurements of blood flow/pressure in response to neurally and pharmacologically evoked erection and in vitro studies of cavernosal tissue reactivity.
Effects of Metabolic Syndrome X on urogenital smooth muscle function:
Several cardiovascular diseases endanger the health of the American people; "Syndrome X" is the most rapidly increasing in incidence. The most widely accepted definition of "Syndrome X" is the combned development of several cardiovascular risk factors including obesity, hypertension, and insulin-resistant (type II) diabetes. A useful animal model with a "Syndrome X"-like phenotype is the Fatty Zucker Rat. Studies currently ongoing in our lab are using this model to determine the nature of urogenital organ disturbances associated with presence of multiple cardiovascular risk factors. Specific focal points in these studies include functional remodeling, changes in the production of nitric oxide and free radicals, and alterations in reactivity to vasoconstrictors in the bladder and corpus cavernosum.
More Research Interests
Associate Professor (2004 - present)
Brody School of Medicine, Department of Physiology
East Carolina State University, Greenville, NC
Research focus: Cell Signaling and Muscle Physiology
Assistant Professor (1998 - 2004)
School of Medicine and Graduate Studies
Department of Physiology and Endocrinology
Medical College of Georgia, Augusta, GA
Assistant Professor of Research (1995 - 1998)
Department of Molecular Physiology and Biological Physics
University of VA, Charlottesville, VA
Postdoctoral Fellow, Physiology (1991 - 1994)
University of Virginia, Charlottesville, VA
Doctor of Philosophy, Biological Sciences (1986 - 1991)
Wayne State University, Detroit, MI
Master in Biological Sciences (1984 - 1986)
University of Washington, Seattle,
Bachelor of Science, Biology (1980 - 1984)
Hiram College, Hiram, OH
For a full list of Pubmed citations, click here.
American Society for Pharmacology and Experimental Therapeutics (Regular Member, 2000)
Sexual Medicine Society of North America (Affiliate Member 2000)
Biophysical Society (Senior Member, 1993).
American Physiological Society, (Full 1993).
American Heart Association Scientific Council, Basic Science (1993).
Member of American Heart Association, Mid-Atlantic Consortium Study Section, Mid-Atlantic Consortium-2, Baltimore, MD, 2005-present.
Reviewer Health Effects Institute, Boston, MA, March 2005.
National Institutes of Health, NIGMS, ad hoc SCORE reviewer, February 2005.
National Institutes of Health Urology Special Emphasis Panel, reviewer, Washington D.C., July 2004.
Co-Chair of ASPET Symposium on Integrative Pharmacology, "From calcium mobilization to calcium sensitivity: Identification of new pharmacological targets in smooth muscle", Experimental Biology Meeting, Washington DC, 2004.
National Institutes of Health Urology Special Emphasis Panel, reviewer, Washington D.C., March 2003.
External Reviewer for Albert Einstein College of Medicine, Diabetes Center Research Grant Proposal, July 2002.
Recent Funding and Sources
Phillip Morris Research Foundation, Adenosine Signaling and Vascular Endothelial Dysfunction Following Fine Airborne Particulate Matter Exposures, P.I. Dr. C.J. Wingard, 09/01/2005 - 08/31/2008.
NIH/NIDDKD (1 RO1 DK59467-01) Erectile Function and the Influence of Rho-kinase, P.I., Dr. C. J. Wingard 09/01/2001 - 08/30/2006.
NIH/NHLB (RO1 HL071138-01) Nitric Oxide Inhibits RhoA/Rho-kinase in Penile Erection, P.I., Dr. R. C. Webb 04/1/03 – 03/31/07.
NIH/NHLB (2 RO1 HL58027-5) Heat Shock Proteins and Vasospasm, P.I., Dr. Colleen Brophy, 04/01/01 – 03/31/06.
American Health Assistance Foundation, National Heart Foundation (H2000011), Nitrovasodilator Modulation of Arterial Function, P.I., Dr. C. J. Wingard, 4/1/2000 - 3/31/2002.
American Heart Association Southeast Regional, Grant in Aid (9960075V), Cellular and Energetic Determinates of Arterial Smooth Muscle Nitrovasodilator Induced Relaxation, P.I., Dr. C. J. Wingard, 7/1/1999 - 6/30/2002.