Research

Life Sciences & Biotechnology

Title :

Study of Epigenetic regulation of ERK5 by histone methylase, Enhancer of Zeste Homolog (EZH)-2, during ox-LDL-induced endothelial to mesenchymal transition (EndMT)

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Prof. Umesh CS Yadav, Jawaharlal Nehru University, New Delhi

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

Endothelial to mesenchymal transition (EndMT) is a cellular pathological process that occurs during embryonic development and is linked to diseases like endothelial dysfunction (ED) and atherosclerosis. The increase in oxidized-low density lipoprotein (oxLDL) levels during metabolic disorders creates an oxidative microenvironment in the vasculature, affecting endothelial cells (ECs) function and homeostasis. Exposure to oxLDL leads to decreased Erk5 expression, downregulation of endothelial cell marker genes, and increased expression of inflammatory markers. These alterations can compromise EC homeostasis and promote ED. However, the mechanism of epigenetic modifications enabled during EndMT and its impact on key EC and mesenchymal marker genes is unknown. The study proposes investigating how oxLDL-rich environments enable EZH2 mediated epigenetic modifications in Erk5 gene expression and promote EndMT during metabolic stress conditions. The aim is to identify and validate EZH2 histone methylase as a novel therapeutic target for preventing and treating atherosclerosis in metabolically predisposed individuals. The study aims to unravel the crosstalk between Erk5 and EZH2, identifying a novel target for the prevention and therapy of metabolic stress-induced atherosclerosis.

Co-PI:

Prof. Rakesh K. Tyagi, Jawaharlal Nehru University, New Delhi-110067

Total Budget (INR):

71,41,640

Organizations involved