My research interest lies in the investigations of the (dys)functional regulation of the cardio-vascular, renal and metabolic systems. During my graduate training, I was very interested in cellular redox mechanisms and their role in the regulation of cardiovascular function. I examined the interplay of the heme-heme oxygenase system, a crucial cellular antioxidant pathway, with reactive species and gases including, carbon monoxide, nitric oxide, and hydrogen peroxide. I uncovered a novel regulatory pathway that governs the dual vascular effects hydrogen peroxide on the renal vasculature. We showed that broad-spectrum antioxidants can condition the renal vascular response to hydrogen peroxide, which can cause vasodilation via increased heme oxygenase activity and carbon monoxide production. In the absence of such conditioning, hydrogen peroxide interferes with heme oxygenase activity and causes thromboxane-induced vasoconstriction. I further pursued my interests in redox biology and heme-heme oxygenase system, in the regulation of cardio-metabolic systems, during my postdoctoral fellowship and early years as a junior faculty. My interests expanded to the study of the human mesenchymal cells, and their regulation by oxidative stress. I published a number of manuscripts, with my co-authors, on the effects of reactive oxygen species on the adipogenic potential of human MSCs. We demonstrated the protective role of the heme-heme oxygenase system in this setting and established alternate therapeutic options for obesity.
During the past 3-years, I have been deeply involved in a number of diverse projects with my collaborators. In conjunction with Dr. Kumar, I have expanded my research endeavors to include transcriptional regulation of genes of the renin-angiotensin-system (RAS) with implications for vascular function and blood pressure regulation. I am focused on the physiological effects of haplotype-dependent regulation of the RAS axis and my work includes the use of novel techniques like, the wire myograph, telemetric implantations, and generation and study of humanized transgenic mice. We have uncovered gene-regulatory pathways that can alter the transcription of gene like angiotensinogen and aldosterone synthase under various pathophysiological conditions including, aging and obesity. We have shown that these effects are haplotype-dependent and are modulated by previously unknown mechanisms including, the intronic regulation of gene-expression. These studies bring us one-step closer to the goal of personalized medicine by identifying “at risk” individuals for the devolvement of hypertension and metabolic syndrome. I am the co-investigator on this grant, and we are funded by the NIH through 2019.
Additionally, in collaboration with Dr. Sodhi, I am involved in the study of redox mediators in obesity and non-alcoholic fatty liver disease (NAFLD). We study the interplay of the heme-heme oxygenase system and the ubiquitous NAD-dependent deacetylase, Sirtuin1, in the pathophysiology of NAFLD. Importantly, we are also exploring the role of the Na/K-ATPase-Src amplification loop in hepatocyte signaling and the development of the NAFLD.