Projects
Mechanistic insights into epigenetic layers involved in impaired wound healing and cardiovascular diseases in diabetes
Our Lab will focus on diabetes wound healing a type of diabetic complication. Diabetes wound healing is highly prevalent in our community and a major cause of morbidity and mortality. Impaired wound healing due to diabetes can lead to chronic wounds and amputation of the foot. Furthermore, currently available drugs for these disorders are not fully efficacious in many patients. Macrophage dysfunction is an important feature of diabetic wound healing characterized by altered M1 and M2 populations through the action of TNF-α and TGF-β1 respectively. Although biochemical mechanisms involved in diabetic wound healing have been studied, contributing epigenetic mechanisms are not well known. We will investigate the functional roles of enhancers/SEs and lncRNAs in diabetic wound healing-associated gene expression and phenotypes in macrophages. We will use experimental as well as computational methods to address those questions. The ultimate goal is to uncover enhancer/SE and lncRNA-dependent mechanisms for TNF-α and TGF-β1 actions in monocytes and macrophages that can lead to identification of new therapeutic targets for diabetic wound healing.
Molecular mechanisms of diabetes and Angiotensin II induced phenotypic switching in vascular smooth muscle cells
Vascular smooth muscle cell (VSMC) possess unique features that allow them to de-differentiate in response to angiotensin II (AngII), via a process called phenotypic switching. Diabetic conditions promote VSMC phenotypic switching and accelerate Cardiovascular disease (CVD). However, the molecular mechanisms involved in VSMC phenotypic switching under diabetes and AngII stimulation are unknown. To answer this, we are collaborating with Dr. Rama Natarajan’s lab in the area of diabetes-induced phenotypic switching of VSMC and its implications in CVD by utilizing state-of-the-art multi-omic approaches including single-cell transcriptomic and epigenomic analyses.
Collaborators:
Dr. Dustin E. Schones Beckman Research Institute of City of HopeCalifornia, USA
Dr. Kaustabh GhoshUniversity of California, Los AngelesDoheny Eye InstituteCalifornia, USA
Dr. Rama NatarajanBeckman Research Institute of City of HopeCalifornia, USA
Dr. Parijat SenapatiRGCB, TrivandrumIndia
Dr. Amit LahiriCSIR-CDRI, LucknowIndia
Dr. Jogender SinghIISER-MohaliIndia