Department of Pathology
Director, Center for Free Radical Biology
Vice-Chair of Research Department of Pathology
Department of Pathology, School of Medicine
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.
Mechanisms of Cell Signaling by Mitochondria in Physiology and Disease
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.