The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 Nathan S. Bryan, Ph.D.

Nathan S. Bryan, Ph.D.

Assistant Professor, Texas Therapeutics Institute

Nathan.Bryan@uth.tmc.edu

713-500-2439

Dr. Bryan earned his undergraduate degree in Biochemistry from the University of Texas at Austin and his doctoral degree from Louisiana State University School of Medicine in Shreveport where he was the recipient of the Dean's Award for Excellence in Research.  He pursued his post-doctoral training as a Kirschstein Fellow at Boston University School of Medicine in the Whitaker Cardiovascular Institute.  Dr. Bryan joined the Institute of Molecular Medicine, University of Texas-Houston, in June 2006 as an Instructor in the Center for Cell Signaling.  He is also a faculty member of the Department of Integrative Biology and Pharmacology at the Medical School, and a member of the Nitric Oxide Society, Society for Free Radical Biology and Medicine and the American Heart Association and presently he is an Assistant Professor in the deparment of Texas Therapeutic Institute.

Nitric Oxide Pathway

Dr. Bryan's research is dedicated to providing a better understanding of the interactions of nitric oxide (NO) and related metabolites with their different biological targets at the molecular and cellular level and the significance of these reactions for physiology and pathophysiology using systems biology approach.  Attempts are made to identify what particular changes in NO-related signaling pathways and reaction products occur in disease states such as endothelial dysfunction, ischemia/reperfusion, tissue/cardiac protection, diabetes, atherosclerosis and inflammation with the aim of testing their amenability as biomarkers for diagnosis and/or treatment of specific disease, providing an interface between analytical biochemistry, physiology/pharmacology and medicine.  

Current research is directed to understand the interactions of exogenous dietary nitrite/nitrate (NOx) on the endogenous NO/cGMP pathway and how perturbations in each system affect cardiovascular health.  This involves mechanisms of nitrite transport and cellular uptake as well as mechanism of nitrite reduction back to NO and via direct NO-independent signaling actions of nitrite.  Work in Dr. Bryan's lab involves molecular biology and analytical biochemistry utilizing gas phase chemiluminescence and HPLC in multiple organ systems and blood.  Much of the work involves in vivo characterization of NO/nitrite metabolism using a number of transgenic and knockout animal models of disease.  Dr. Bryan and colleagues recently discovered that nitrite is a biologically active molecule which was previously thought to be an inert breakdown product of NO production.  Since nitrite and nitrate are common constituents of many fruits and vegetables, changes in dietary habits may have profound effects on many diseases associated with NO insufficiency.  NO insufficiency is a hallmark of a number of diseases including cardiovascular disease.  The notion that nitrite can be recycled back to NO may serve as an alternative and compensatory mechanism of NO production and may serve as the endocrine mediator of NO signaling.  Moreover, the direct signaling actions of nitrite may represent a novel NO independent pathway for nitrite.  If our current understanding is true, then an optimal diet may then consist of a sufficient supply of nitrite and nitrate for health and disease prevention.   Understanding this pathway will provide the basis for new preventive or therapeutic strategies in diseases associated with NO insufficiency and new guidelines for optimal health.

The Nitric Oxide Solution (NO) Dr. N. Bryan

Publications:

Bryan NS. Nitrite in NO biology:  Cause or consequence? A systems-based review. Free Radic Biol Med 2006, 41:691-701.

Duranski MR, Elrod JW, Calvert JW, Bryan NS, Feelisch M, Lefer DJ.  Genetic overexpression of eNOS attenuates hepatic ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2006, 291:H2980-6.

Wang X, Bryan NS, MacArthur PH, Rodriguez J, Gladwin MT, Feelisch M. Measurement of nitric oxide levels in the red cell: Validation of triiodide based chemiluminsence with acid-sufanilamide pretreatment. J Biol Chem 2006, 281: 26994-7002.

Elrod JW, Greer JJ, Bryan NS, Langston W, Szot JF, Gebregzlabher H, Janssens S, Feelisch M, Lefer, DJ. Cardiomyocyte-specific overexpression of NO synthase-3 protects against myocardial ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 2006, 26: 1517-23.

Peyrot F, Fernandez BO, Bryan NS, Feelisch M, Ducrocq C. N-Nitroso products from the reaction of indoles with angeli's salt. Chem Res Toxicol 2006, 19: 58-67.

Zamora R, Bryan NS, Boyle P, Wong C, Milsom AB, Jaffe R, Feelisch M, Ford HR. Nitrosative stress in an animal model of necrotizing enterocolitis. Free Radic Biol Med 2005, 39: 1428-37.

Bryan NS, Fernandez BO, Garcia-Saura MF, Bauer SM, Milsom AB, Rassaf T, Maloney R, Bharti A, Rodriguez J, Feelisch M. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nature Chemical Biology 2005, 1: 290-7.

Janero DR, Bryan NS, Saijo F, Dhawan V, Schwalb, DJ, Warren MC, Feelisch M. Differential nitros(yl)ation of blood and tissue constituents during glyceryl trinitrate biotransformation in vivo. Proc Natl Acad Sci USA 2004, 101: 16958-63.

Tao L, Gao E, Bryan NS, Ou Y, Liu HR, Hu A, Christopher TA, Lopez BL, Yodio J, Koch WJ, Feelisch M, Ma XL. Cardioprotective effects of thioredoxin in myocardial ischemia and reperfusion:  the role of S-nitrosation. Proc Natl Acad Sci USA 2004, 101: 11471-6.

Bryan NS, Rassaf T, Rodriguez J, Feelisch M. Bound NO in human red blood cells:  fact or artifact? Nitric Oxide 2004, 10: 221-8.

Bryan NS, Rassaf T, Rodriguez C, Maloney R, Saijo F, Rodriguez J, Feelisch M. Cellular targets and mechanisms of nitros(yl)ation:  A first insight into their nature and kinetics in vivo. Proc Natl Acad Sci USA 2004, 101: 4308-4313.

Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Godecke A, Schrader J, Schulz R, Heusch G, Schaub GA, Bryan NS, Feelisch M, Kelm M. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med 2003, 35: 790-6.

Rassaf T, Bryan NS, Maloney RE, Specian V, Kelm M, Kalyananraman B, Rodriguez J, Feelisch M. NO adducts in mammalian red blood cells:  too much or too little? Nat Med 2003, 9: 481-3.

Rodriguez J, Maloney RE, Rassaf T, Bryan NS, Feelisch M. Chemical nature of nitric oxide storage forms in rat vascular tissue. Proc Natl Acad Sci USA 2003, 100: 336-41.

Rassaf T, Bryan NS, Kelm M, Feelisch M. Concomitant presence of N-nitroso and S-nitroso proteins in human plasma. Free Radic Biol Med 2002, 33: 1590-6.

Feelisch M, Rassaf T, Mnaimneh S, Singh N, Bryan NS, JourdHeuil D, Kelm M. Concomitant S-,N-, and heme nitros(yl)ation in biological tissues and fluids:  implications for the fate of NO in vivo. FASEB J 2002, 16: 1775-85.

Joshi MS, Ferguson TB, Han TH, Hyduke DR, Liao JC, Rassaf T, Bryan N, Feelisch M, Lancaster JR Jr. Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions. Proc Natl Acad Sci USA 2002, 99: 10341-6