Kidney Diseases are major non-communicable diseases occurring in India, whose presence predicts a severe fold increase in all-cause and cardiovascular mortality. The prevalence of chronic kidney diseases has been doubled in India in the last few years, signifying urgent requirement of novel therapeutics for kidney diseases; an unmet medical need. The SRMulay laboratory at CSIR-CDRI is interested in understanding the contribution of regulated necrosis pathways and inflammation in the initiation and progression of acute and chronic kidney diseases. In addition, the laboratory is involved in deciphering molecular pathomechanisms of various crystals- or crystalline particles-associated diseases called crystallopathies. The major objective of the research group is to understand the complex disease biology in order to identify as well as validate novel druggable targets using experimental animal models.
Uncontrolled inflammation causes alterations in tissue homeostasis and leads to tissue pathology. Renal inflammation actively participates in renal damage in both acute kidney injury (AKI) and chronic kidney diseases (CKD). Inflammation and tissue injury are tightly linked processes that amplify each other leading to a vicious cycle, which is termed as necroinflammation. We work on the hypothesis that necroinflammation drives acute tissue injuries, as well as that the persistent necroinflammation modulate chronic tissue remodeling e.g. kidney fibrosis. Furthermore, deposits of crystals, misfolded proteins, or airborne particulate matter of nanoparticle or microparticle size cause diverse medical disorders that are called crystallopathies, which can manifest into either acute or chronic organ injuries. We discovered that these crystals- or crystalline particles, when deposited in the kidney, induce cell necrosis involving various pathways of regulated necrosis and inflammation. We are determined to understand the molecular mechanisms of kidney necroinflammation during the development of various kidney diseases and crystallopathies, which facilitate the identification of novel druggable targets. We validate these targets using various in-vitro and in-vivo experimental disease models using genetic as well as pharmacological approaches.
The broader aim of the laboratory is to contribute to the development of novel therapies to restrict regulated necrosis and inflammation i.e. necroinflammation. Therefore, we screen synthetic and natural compound libraries of CSIR-CDRI in a systematic manner using in-vitro assays to find potential drug candidates. Further, we evaluate the lead compounds in-vivo using experimental animal models in a “therapeutic” study design with predefined primary and secondary study endpoints.