Priyatansh Gurha

My primary research objective is to gain insight into the molecular mechanisms that regulate gene expression and contribute to the pathogenesis of heart failure. Within the context of this theme, we are investigating the role of epigenetics and non-coding RNAs in the proliferation, differentiation, and maturation of myocytes, as well as how perturbation of these interdependent processes ultimately results in cardiac dysfunction and failure. The epigenetic dysregulation of miR-184 and its role in the pathogenesis of ACM were identified in our previous research. In heart failure (HF), we are investigating how reprogramming of epigenetic code regulates gene transcription and the resulting cardiac phenotype. Recent research has revealed the significance of DNA methylation and Lamin Associated Domain in Human HF. These studies led to the identification of the KDM5 family of demethylases in the phenotype of HF. The function of KDM5 in the physiology and pathophysiology of the heart remains unknown. We are investigating the cell-type-specific contribution of these regulators to cardiac physiology using induced pluripotent stem cells (iPSCs) and multiple mouse models. We discovered that KDM5 directly affects the maturation of iPSC-CMs. The reprogramming of iPSC-CM toward a maturation state is partially governed by KDM5 mediated epigenetic regulation of genes implicated in OXPHOS and sarcomere formation. We recently implicate KDM5 as epigenetic regulators of dysregulated genes in HF caused by LMNA Loss of Function. The results suggest that KDM5A and KDM5B are involved inthe pathogenesis of HF.Utilizing Gain of function and Loss of function approaches, the roles and underlying mechanisms governed by KDM5A and KDM5B in HF are been investigated. To address these problems, we take a multidisciplinary strategy that combines mouse genetics, biochemistry, and genomics. 1. Research Projects: - Role of KDM5 family of Histone Demethylases in Heart - Epigenetic regulatory mechanisms in Cardiomyopathies and heart failure - Role of non-coding RNAs in Heart failure