E-mail: agarwal@uab.edu

Research/Clinical Interest Description: My research efforts include three main areas. (i) We are studying the molecular regulation of the human heme oxygenase-1 (HO-1) gene in renal injury and in atherosclerosis. 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, angiogenesis 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. (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 renal injury, transplantation and atherosclerosis. (iii) We are actively pursuing gene delivery approaches in the kidney and the vasculature in animal models of transplantation 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 in the kidney.