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Faculty Detail     Name VICTOR M DARLEY-USMAR   Campus Address BMR2 508 Zip 2180 Phone 205-975-9686 E-mail darley@uab.edu Other websites

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Pathology   Pathology Gen Administration Professor Secondary  Anesthesiology   Anesthesiology Chair Office Professor Secondary  Neurobiology  Neurobiology Professor Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor Center  Medicine  Comprehensive Diabetes Ctr Professor Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Professor Center  Medicine  Ctr Cardiovasc Bio Professor Center  Medicine  Nephrology Res & Trng Ctr Professor

Graduate Biomedical Sciences Affiliations Cellular and Molecular Biology Program  Hughes Med-Grad Fellowship Program  Integrative Biomedical Sciences  Medical Scientist Training Program  Molecular and Cellular Pathology Program

Biographical Sketch  Dr. Darley-Usmar is the UAB Endowed Professor in Mitochondrial Medicine and Pathology. He serves as the Vice Chair of Research for the Department of Pathology and Director of the Center for Free Radical Biology at UAB. His research program focuses on redox cell signaling and molecular bioenergetics in the pathogenesis of human disease. He received his Ph.D. training from Dr. M.T. Wilson at the University of Essex which was to define the structure and function of cytochrome c oxidase. This involved defining whether the monomer or dimer of the enzyme was active and applying the then new techniques of SDS-polyacrylamide gel electrophoresis to membrane proteins. He continued to pursue his interest in mitochondrial proteins with Dr. R. A. Capaldi at the University of Oregon and was one of the first to use Western Blotting to understand the molecular pathology of a mitochondrial myopathy. On returning to the UK after two years as an Assistant Professor in Japan he first became interested in the area of nitric oxide research in industry as a Research Scientist at Wellcome Research Laboratories. Over a ten year period there he worked on the interactions of nitric oxide with reactive oxygen species and mitochondria. Working with Salvador Moncada and Tony Schapira (Royal Free Hospital) he was one of the first to discover that nitric oxide can interact reversibly with cytochrome c oxidase and so control respiration. He left the UK in 1995 to join the Free Radical group at UAB led by Bruce Freeman. Currently he is developing novel methods to assess the measurement of oxidative stress in mitochondria and defining how we determine the mitochondrial response to oxidative stress in the pathologies associated with bioenergetic dysfunction.

Society Memberships Organization Name Position Held Org Link American Physiological Society  Member    Biochemical Society  Member    Society For Free Radical Biology and Medicine  former President

Research/Clinical Interest Title Mechanisms of Cell Signaling by Mitochondria in Physiology and Disease Description Among the most serious diseases that effect developed nations are those involving chronic and acute inflammation. Typical examples include atherosclerosis and the vascular complications of hypertension and diabetes. We now know that this is mainly due to the production of reactive oxygen and nitrogen species and their interactions with cell signaling pathways. The focus of our laboratory is to understand how the signaling pathways are altered in pathologies associated with oxidative stress and how mitochondrial dysfunction plays a part in this. Two areas of bioenergetic research are of particular interest. 1) Those involving oxidized lipids as signaling molecules and 2) the free radical signaling molecule nitric oxide. Nitric oxide is one of the beneficial free radicals in the artery wall and in a series of studies over the last few years we are determining how it exerts protection over the vasculature. We are particularly interested in how the interaction of mitochondria with NO can modulate cell signaling. With an extensive network of collaborators in UAB and at other national and international institutions we are defining the molecular events which control mitochondrial function in disease and designing mitochondrial therapeutics. Our approach is to use our insight into the biochemistry of free radicals and bioenergetics to understand events at the cellular level. We use molecular biology, proteomics and cellular approaches to address these problems.

Selected Publications  Publication PUBMEDID Chacko, B. K., Srivastava, A., Johnson, M. S., Benavides, G. A., Chang, M. J., Ye, Y., Jhala, N., Murphy, M. P., Kalyanaraman, B. and Darley-Usmar, V. M. Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosis. Hepatology. 54, 153-163 2011.  21520201  Chacko BK, Reily C, Srivastava A, Johnson MS, Ye Y, Ulasova E, Agarwal A, Zinn KR, Murphy MP, Kalyanaraman B, Darley-Usmar V. Prevention of diabetic nephropathy in Ins2(+/)(AkitaJ) mice by the mitochondria-targeted therapy MitoQ. Biochem J;432:9-19. 2010  20825366  Hill BG, Dranka BP, Bailey S, Lancaster J, Darley-Usmar V. What part of NO don't you understand? Some answers to the cardinal questions in nitric oxide biology. J Biol Chem, 285, 19699-19704, 2010  20410298  Perez J, Hill BG, Benevides GA, Dranka BP, Darley-Usmar V. Role of Cellular bioenergetics in smooth muscle cell proliferation induced by platelet-derived growth factor. Biochem J, 2010 428(2):255-67  20331438  Dranka, B. P., Hill, B. G. and Darley-Usmar, V. M. Mitochondrial reserve capacity in endothelial cells: The impact of nitric oxide and reactive oxygen species. Free Radic Biol Med 48, 905-914, 2010.  20093177  Hill BG, Higdon AN, Dranka BP, and Darley-Usmar VM. Regulation of vascular smooth muscle cell bioenergetic function by protein glutathiolation. Biochim Biophys Acta, 1797(2):285-95, 2010.  19925774  Hill BG, Dranka BP, Zou L, Chatham JC, and Darley-Usmar VM. Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal. Biochem J 424: 99-107, 2009.  19740075  Higdon AN, Dranka BP, Hill BG, Oh JY, Johnson MS, Landar A, and Darley-Usmar VM. Methods for imaging and detecting modification of proteins by reactive lipid species. Free Radic Biol Med 47: 201-212, 2009.  19446632  Oh, J. Y., Giles, N., Landar, A. and Darley-Usmar, V. (2008) Accumulation of 15-deoxy-delta(12,14)-prostaglandin J2 adduct formation with Keap1 over time: effects on potency for intracellular antioxidant defence induction. Biochem J 411, 297-306  18237271

Keywords cardiovascular, mitochondria, nitric oxide, reactive oxygen species, hepatotoxicity

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