The Scindia lab specializes in investigating the mechanisms by which dysregulation of iron metabolism in immune and non-immune cells contributes to kidney pathology. Inflammation, tissue injury and progression to organ failure perturb local and systemic iron homeostasis. We strive to identify novel iron centric mechanisms and targets for intervention. After in vivo validation, we collaborate with industry and test novel molecules. We aim to develop novel strategies to treat pathologies still managed mainly by fluid management (Sepsis) and traditional immunosuppression (Autoimmune disorders).
My lab utilizes human tissue and genetically manipulated rodent models with dysregulated iron metabolism and compartmentalization in renal epithelial cells, myeloid cells and CD4+ve T cells to dissect fine mechanisms of acute kidney injury, systemic lupus erythematosus and lupus nephritis. I am a passionate teacher with a Socratic mentoring philosophy.
My research focuses on:
1) Autoimmunity and autoimmune kidney disease: We have identified occurrence ferroptosis (iron dependent form of regulated inflammatory cell death) in the kidneys in both human and murine lupus nephritis, the most common and devastating end-organ pathology of systemic lupus erythematosus (SLE). We investigate the genetic and cellular mechanisms contributing to ferroptosis and how iron dyshomeostasis in parenchymal and immune cells (with focus on macrophages and CD4+ T cells) impacts outcomes of SLE and lupus nephritis. Ferroptosis is a druggable therapeutic target, and our ongoing studies using novel ferroptosis inhibitors may identify ferroptosis inhibitors as novel therapeutics to treat autoimmune kidney disease.
2) Iron dyshomeostasis and pyelonephritis: Candida auris and Candida albicans are two of the four fungi listed in the critical priority group by the World Health Organization. A sizable population of patients with liver disease have high susceptibility to these fungal infections. These patients also present with low levels of hepcidin. Hepcidin, a hepatocyte derived prohormone is the master regulator of systemic iron metabolism. Iron is an essential micronutrient for both the host and pathogens. Hepcidin-induced retention of iron within cells is a critical physiological adaptation against invading pathogens. We investigate how loss of hepcidin and improper iron compartmentalization influences outcomes of fungal pyelonephritis using human tissue and animal models of infection. We evaluate the efficacy of clinical and research stage hepcidin mimetics as possible interventions in animal models. Our studies may facilitate clinical trials to design novel management strategies to reduce the risk of infections in critically ill patients, especially ones with liver disease.