The research interests of these investigators involve the role of oxidative stress in tissue damage, especially as this affects diabetes-related complications. Central to this research area is the concept that hyperglycemia generates oxidant stress and that this oxidant stress likely derives from glucose-induced superoxide generation by mitochondria. This excess superoxide escapes the mitochondria and generates toxic downstream products that damage cellular DNA and enzymes crucial for normal cellular glucose utilization. This, in turn, shunts glucose down pathways that are known to be involved in diabetes complications, including the polyol pathway, advanced glycosylation end-product formation, activation of protein kinase C and subsequently NFκ B, and the hexosamine pathway. Activation of these pathways contributes both to the microvascular and macrovascular complications of diabetes. Many of the investigators in this group also focus on the atherosclerosis-related complications of diabetes, especially as this relates to endothelial dysfunction and the role of macrophages in generating the atherosclerotic plaques.