Department of Clinical and Experimental Therapeutics,
University of Georgia, Augusta, USA
I am currently a postdoctoral Associate in Clinical and experimental Therapeutics, College of Pharmacy, at University of Georgia. My current interest to study the role and regulation of neurotrophins pathway during diabetic complication. We are looking for small non-peptide molecules to target neurotrophins pathway to overcome diabetic vascular complications especially during diabetic nephropathy and retinopathy. My academic training and research experience so far have provided me with an excellent background in multiple biological disciplines including molecular biology, Immunology and biochemistry, especially in the field of vascular inflammation and microvascular dysfunction. In my postdoctoral training in the Vascular Biology Center at Augusta University, I gained experience in diabetic studies that focused on netrin-1 and Cytokine Il17 and its isoforms in relation to acute and diabetic kidney disease. I was awarded the prestigious postdoctoral Fellowship from American Heart Association. This fellowship allowed me to expand my interest in diabetes-induced inflammation research in acute and chronic kidney diseases. We used specific transgenic and knockout animals and cell lines to understand the role and regulation of endogenous anti-inflammatory molecule Netrin-1, pro-inflammatory molecule semaphorin 3A in diabetes and kidney diseases. We have shown that Netrin-1 has anti-inflammatory effect by inhibiting NFkb induced COX-2 activation whereas, semaphorin 3A has proinflammtory effect on kidney cell during both acute and chronic kidney diseases. In parallel, we observed that IL-17 levels were elevated in the urine from microalbuminuric diabetic patients and mice, but interestingly, these levels were significantly reduced with DN progression. Low dose IL-17 therapy prevents and reverses diabetic nephropathy, metabolic syndrome and associated organ fibrosis. Il17A induces AMWAP expression in epithelial cell which convert M1 macrophages to a less inflammatory M2 phenotype. This is first report to show potential ability of IL-17A to protect against diabetic nephropathy. This research led to many publications in peer-reviewed journals. In my transition to be an independent investigator, I moved to the Retinopathy lab so I can complement my prior nephropathy expertise with retinopathy as they share multiple aspects of pathophysiology. Previously our lab shown that diabetes disturbs the homeostasis of the nerve growth factor (NGF) resulting in accumulation of its precursor proNGF and decrease in NGF resulted in activation of p75NTR cell death pathway in retinas. The focus of the current research project is to understand role and regulation of neurotrophins in diabetes induced microvascular complication in both kidney and eye. We are using endothelial specific proNGF transgenic mice as well as p75NTR antagonist (small non peptide molecules) to target proNGF/p75NTR pathway to overcome diabetes induced vascular complications.