Primary Department Affiliation: Pathology
Among the most serious diseases that effect developed nations are those involving the cardiovascular system. Typical examples include atherosclerosis and the vascular complications of hypertension and diabetes. We now that that this is mainly due to the production of free radicals and their interactions in the cells of the artery wall. The focus of our laboratory is to understand how the signaling pathways are altered in vascular disease and how free radicals play a part in this. Two areas are of particular interest:
- Those involving oxidized lipoproteins and
- 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 at UAB and at other national and international institutions we are defining the molecular events which control NO signaling pathways in the diseased vessel wall. Our approach is to use our insight into the biochemistry of free radicals to understand events at the cellular level. Recently, we have found that NO activates a previously uncharacterized signal pathway in the mitochondrion that increases synthesis of intracellular antioxidants in the cell in addition to directly inactivating damaging free radicals. The risk for cardiovascular disease is not the same throughout the world and some of these differences are due to diet. We are also working on how dietary components such as the polyphenolics in red wine can protect the vascular system and have identified novel mechanisms through which this can be achieved. We use molecular biology, proteomics and cellular approaches to address these problems.
Darley-Usmar is presently Professor of Pathology and a founder member of the Center for Free Radical Biology at UAB. In this role, he is able to combine major research interests in mitochondriology and reactive oxygen and nitrogen species the aim of understanding the mechanisms of cell death in cardiovascular disease. He was trained as a biochemist at the University of Essex in England and then moved to the University of Oregon to pursue his interests in the structure and function of mitochondrial proteins in human disease. After a period as a lecturer in Japan and a Research Scientist at Wellcome research