Medical University | MUSC Hospital | Directory | A-Z Index

Gazes Cardiac Research Institute

MUSC logo

ART

 Gazes Cardiac Research Institute | faculty | Paul J. McDermott, Ph.D.

Paul J. McDermott, Ph.D.

Partial or complete occlusion of a coronary artery creates ischemia, therby exposing the myocardium to either an insufficient supply of oxygen (hypoxia) or a complete lack of oxygen (anoxia).  The resulting myocardial damage is dependent on multiple variables such as the extent and duration of oxygen deprivation and the deleterious effects produced during reoxygenation of the myocardium (ischemia/reperfusion).  To minimize adverse effects on cardiac structure and function, the myocardium undergoes adaptive remodeling that includes a switch to glycolytic metabolism in the cardiomyocyte.  This switch in the energy metabolism is a common characteristic of ischemic heart disease and other causes of heart failure.  My laboratory is focused on the mechanisms that regulate myocardial protien synthesis during adaptive growth and remodeling in cardiac muscle cells (cardiomyocytes).  Using adult cardiomyocytes in primary cell culture, an electrical stimulation system has been developed to generate continuous contractile activity in normoxic versus hypoxic conditions.  Ongoing studies with this model are examining how oxidative stress as produced by either hypoxia or hypoxia/reoxygenation affects expression of Estrogen-related Receptor (ERR) isoforms in contracting cardiomyocytes.  ERRs belong to a nuclear receptor superfamily that regulates transcripton of a wide array of target genes involved in uptake of energy substrates, oxidative phosphorylation and metabolism of fatty acids and glucose.  Although ERRs do not require ligand binding for activation, they are coactivated during oxidative stress by the master regulatory protien called Peroxisome Proliferator-Activated Receptor ƳCoactivator (PGC-1α).  In addition to transcriptional activation, recent findings indicate that ERR expression in adult cardiomyocytes is regulated in response to hypoxia and reoxygenation by translational effeciency and/or mRNA stability.  ERR mRNA has structural features and sequence elements in the 5'-UTR and 3'-UTR that are characteristic of post-transcriptional regulation.  These include a 5'-UTR with extensive secondary structure in the form of a large, stable hairpin loop near the 5'cap, and a relatively long 3'-UTR that has possible AU-rich elements involved in translation-linked mRNA stability.  In companion studies, a murine model of myocardial ischemia and ischemia/reperfusion injury is employed to determine the physiological relevance of the in vitro cardiomyocyte model to oxidative stress in vivo.  By determining how ERR expression is regulated in response to oxidative stress, the overall goal of these studies is to characterize the mechanisms that alter cardiac energetics and fuel metabolism during adverse remodeling and the transition to heart failure.

Dr McDermott's Lab
Laboratory Members
Katie Cribben, M.S.
Daisy Dominick B.S.

 
Publications

Pubmed Listings

Wada, H., Zile, M.R., Ivester, C.T., Cooper IV, G., and McDermott, P.J.: Comparative effects of contraction and angiotensin II on growth of adult feline cardiocytes in primary culture. Amer. J. Physiol., 271:H29-H37, 1996.

Tagawa, H., Rozich, J.D., Tsutsui, H., Narishige, T., Kuppuswamy, D., Sato, H., McDermott, P.J., Koide, M., and Cooper IV, G.: Basis for increased microtubules in pressure hypertrophied cardiocytes. Circulation 93:1230-1243, 1996.

Wada, H., Ivester, C.T., Carabello, B.A., Cooper IV, G., and McDermott, P.J.: Translational initiation factor eIF-4E: A link between cardiac load and protein synthesis. J. Biol. Chem., 271:8359-8364, 1996.

Kent R.L., and McDermott, P.J. Passive load and angiotensin II evoke differential responses of gene expression and protein synthesis in cardiac myocytes. Circ. Res. 78:829-838, 1996.

Yang, Q., McDermott, P.J., Duzic, E., Pleij, C.W.A., Sherlock, J.D., and Lanier, S.M.: The 3' untranslated region of the a2C-adrenergic receptor mRNA impedes translation of the receptor message. J. Biol. Chem., 272:15466-15473, 1997.

Makhlouf, A., and McDermott, P.J.: Increased expression of eukaryotic initiation factor 4E during growth of neonatal rat cardiocytes in vitro. Amer. J. Physiol., 274:H2133-H2142, 1998.

Matsuo, T., Carabello, B.A., Nagatomo, Y., Koide, M., Hamawaki, M., Zile, M.R., and McDermott, P.J.: Mechanisms of cardiac hypertrophy in canine volume overload. Am. J. Physiol., 275:H65-H74, 1998.

Tuxworth Jr., W.J., Wada, H., Ishibashi, Y., and McDermott, P.J.: The role of load in regulating eIF-4F complex formation in adult feline cardiocytes. Amer. J. Physiol., 277:H1273-H1282, 1999.

Paul J. McDermott, Ph.D.

Paul J. McDermott, Ph.D.
Principal Investigator at the Gazes Cardiac Research Institute
Professor of Medicine
Associate Dean for Faculty Affairs and Faculty Development
Research Cell Biologist, Ralph H. Johnson Department of Veterans Affairs Medical Center

Dr. McDermott's Contact Information

Room 303, Gazes/Thurmond Building
114 Doughty St.
Charleston, SC 29403

Phone: (843)789-6839
Lab: (843)789-6844
Fax: (843)876-5068
Email: mcdermp@musc.edu
Dr. McDermott's Education
1979 B.A. Biology, Rowan University
1984 Ph.D. Anatomy and Cell Biology, University of Pittsburgh School of Medicine
1985-1987 Postdoctoral Fellow, Milton S. Hershey Medical Center, Pennsylvania State University