Life Sciences & Biotechnology
Title : | Exploring epigenetic regulation of Shelterin proteins and their role in Cardiovascular Diseases |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Molecular Biology, Cardiovascular Research |
Principal Investigator : | Dr. Syamantak Majumder, Birla Institute Of Technology And Science (BITS), Pilani, Rajasthan |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | syamantak.majumder@pilani.bits-pilani.ac.in |
Details
Executive Summary : | Atherosclerosis is the leading cause of death globally, accounting for 17.9 million deaths in 2019. The development of atherosclerosis is primarily driven by the function of endothelial cells (EC) and their response to fluid shear stress. In arteries, shear stress levels range from 10-70 dyn/cm2, with steady laminar flow (S-flow) associated with increased gene expression beneficial to EC homeostasis. In areas of vessel curvature and branching, shear stress is significantly lower (less than 4 dyn/cm2) and the flow pattern is disturbed (D-flow), characterized by recirculation and oscillations. These areas are more prone to atherosclerosis development due to endothelial dysfunction. Epigenetic changes such as DNA methylation and histone acetylation have been identified as linked to D-flow-mediated EC dysfunction. Preliminary work has shown that many Shelterin-associated proteins, including TRF2 and TPP1, are significantly elevated in EC or rat aorta exposed to TNF alpha. These alterations in the expression of Shelterin-associated protein, specifically TRF2, are sensitive to pharmacological inhibitors of the methyltransferase catalyzing the formation of H3K4me3.
The study proposes exploring the epigenetic regulation of proteins associated with the Shelterin complex, specifically evaluating the role of TRF2 on endothelial inflammation, cellular senescence, and apoptosis supporting atherosclerosis onset and progression. The study aims to establish the epigenetic mechanisms associated with the regulation of Shelterin complex in endothelial cells exposed to pro-inflammatory conditions and elaborate on the role of Shelterin complex and its associated protein, TRF2. |
Co-PI: | Dr. Praphulla Chandra Shukla, Indian Institute Of Technology (IIT) Kharagpur, West Bengal-721302 |
Total Budget (INR): | 64,05,303 |
Organizations involved