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Anupam Agarwal, MD
Birmingham, AL USA

Anupam Agarwal, MD Professor of Medicine, Director, Division of Nephrology. Dr. Agarwal's research program has provided critical insights regarding the cytoprotective nature and significance of heme oxygenase-1 (HO-1) in vascular and renal inflammation, angiogenesis, transplant biology, and the molecular regulation of the human HO-1 gene. Dr. Agarwal's research efforts include three main areas. (i) His laboratory is studying the molecular regulation of the human heme oxygenase-1 (HO-1) gene in renal injury, transplant rejection, diabetic vascular disease and in atherosclerosis. Studies are also exploring the cellular mechanisms involved in the protective effects of the HO-1 enzyme in renal and vascular injury. Induction of this gene occurs as an adaptive and beneficial response to injury and is protective in several clinically important conditions such as acute renal failure, transplant rejection and atherosclerosis. Studies are focused on identifying regulatory regions in the human HO-1 gene that mediate induction in response to stimuli such as heme, cytokines, nitric oxide, modified lipids and growth factors (eg. transforming growth factor-beta). The studies involve molecular biology techniques to study DNA-protein interactions using chromatin structure analysis, in vivo footprinting, site-directed mutagenesis and gel shift assays. His laboratory is also studying the molecular and biological effects of nitrated lipids on HO-1 gene expression in endothelial cells and in the vasculature. (ii) The functional significance of HO-1 gene expression is also being evaluated using both in vitro and in vivo systems in transgenic animal models of acute kidney injury, immune-mediated injury in the setting of transplantation, diabetes and atherosclerosis. (iii) His laboratory is actively pursuing gene delivery approaches in the kidney and the vasculature in animal models of transplantation and diabetes using recombinant adeno-associated viral vectors. Alternate serotypes and capsid mutants of adeno-associated viral vectors are being developed to maximize gene transfer to the otherwise resistant vascular compartment with a goal towards targeting diabetic micro and macrovascular disease.