William Durante, PhD
Our research focuses on understanding the biology of endogenously derived gases in the circulation. We are particularly interested in determining the regulation and function of nitric oxide (NO) and carbon monoxide (CO) in vascular disease. We have identified cationic amino acid transporters (CATs) and arginase in vascular cells and found that both proteins regulate vascular NO release by affecting the intracellular levels of L-arginine: CATs control the entry of L-arginine into vascular cells while arginase promotes the intracellular catabolism of L-arginine to L-ornithine and urea. Ongoing studies are examining whether alterations in CAT and arginase activity contribute to vascular dysfunction in diabetes and atherosclerosis.
We recently discovered that vascular cells generate CO from the catabolism of heme by the enzyme heme oxygenase-1 (HO-1). Interestingly, numerous pathologic stimuli induce HO-1 gene expression and CO formation, which function in an adaptive manner to limit vascular injury. We are now attempting to identify the specific transcription factors and regulatory elements in the HO-1 promoter responsible for the induction of HO-1. In addition, we are using adenoviral-mediated gene delivery approaches and HO-1-deficient mice to further define the vasoprotective role of the HO-1/CO system. A final line of investigation focuses on defining the signal transduction pathways that trigger the release of NO and CO following the exposure of vascular cells to physiologically relevant hemodynamic forces.
- BS in Pharmacology, University of Toronto, Canada
- MS in Pharmacology, University of Toronto, Canada
- PhD in Pharmacology, University of Toronto, Canada
- Completed Postdoctoral Fellowship, Baylor College of Medicine, Houston, TX
- Joined Department in 2006
- Recipient of an Established Investigatorship from the American Heart Association
- Fellow of the American Heart Association
- Member of the American Heart Association, American Physiological Society, North American Vascular Biology Organization, and American Society for Biochemistry and Molecular Biology
- Member of the Molecular Signaling II study section of the National American Heart Association
- Served as an ad hoc reviewer for the United States Department of Veterans Affairs, the United States Department of Agriculture, The Wellcome Trust, Netherlands Organization for Scientific Research, Phillip Morris External
- Research Program, and the Western Consortium of the American Heart Association
- Research currently funded by the National Institutes of Health and the Juvenile Diabetes Research Foundation
- Liu X, Peyton KJ, Ensenat D, Wang H, Schafer AI, Alam J, and Durante W. Endoplasmic reticulum stress stimulates heme oxygenase-1 gene expression in vascular smooth muscle cells: role in cell survival. J. Biol. Chem. 280:872-877, 2005.
- Tulis DA, Keswani AN, Peyton KJ, Wang H, Schafer AI, and Durante W. Local administration of carbon monoxide inhibits neointima formation in balloon injured rat carotid arteries. Cell. Mol. Biol. 51:441-446, 2005.
- Durante W, Johnson FK, and RA Johnson. Targeting heme oxygenase-1 in the treatment of atherosclerosis. Drug Discovery Today: Therapeutic Strategies 2:201-206, 2005.
- Korthuis RJ and Durante W. Heme oxygenase-1: A pluripotent sentinel limiting the systemic inflammatory response to extremity ischemia and reperfusion. Crit. Care Med. 30:2701-2703, 2005.
- Granada JF, Ensenat D, Keswani AN, Kaluza GL, Liu X, Peyton KJ, Azam MA, Wang H, and Durante W. Single perivascular delivery of mitomycin C stimulates p21 expression and inhibits neointima formation in rat arteries. Arterioscler. Thromb. Vasc. Biol. 25:2343-2348, 2005.
- Johnson FK, Johnson RA, Peyton KJ, and Durante W. Arginase inhibition restores arteriolar endothelial function in Dahl rats with salt-induced hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288:R1057-R1062, 2005.
- Liu X, Reyna SV, Ensenat D, Wang H, Schafer AI, and Durante W. Platelet-derived growth factor stimulates LAT1 gene expression in vascular smooth muscle: role in cell growth. FASEB J. 18:766-770, 2004.
- Reyna SV, Ensenat D, Johnson FK, Wang H, Schafer AI, and Durante W. Cyclic strain stimulates L-proline transport in vascular smooth muscle cells. Am. J. Hypertens. 17:712-717, 2004.
Cell culture, enzyme assays, protein kinase assays, amino acid transport studies, thin layer chromatography, flow cytometry, immunohistochemistry, western and northern blotting, ribonuclease protection assays, PCR cloning, gene promoter studies, electromobility shift assays, ChIP assays, gene therapy, vascular reactivity studies in isolated arteries, platelet aggregation, rodent models of arterial injury and cardiovascular disease.