Research

Life Sciences & Biotechnology

Title :

R7RGS-CaMKII complex functions to attenuate chemo-induced cardiac fibrosis by regulating Nox2-dependent inter-communication of different cell types

Area of research :

Life Sciences & Biotechnology

Focus area :

Cardiac Biology, Molecular Biology

Principal Investigator :

Dr. Biswanath Maity, Centre Of Biomedical Research, Delhi

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Details

Executive Summary :

Chemotherapeutics are life-saving drugs, but their clinical use is limited by irreversible, dose-dependent, and life-threatening cardiotoxicity. This leads to cardiac cell death, left ventricular dysfunction, stiffening of heart muscle, compromised automaticity, and fibrosis, which is common in prolonged cancer treatment, particularly among juvenile cancer survivors. The onco-cardiology phenotype is a double-edged sword, as clinicians cannot continue chemo-treatment post-onset of cardiac phenotype, compromising cancer treatment outcomes. The mechanism of chemo-induced cardiac fibrosis is still unclear, and no single mediator has been discovered to attenuate this. The response of different cardiac cell types and their intricate coordination with chemo-induced fibrosis has never been called for. Recent unpublished findings suggest that the loss of communication between different cardiac cell types due to chemo-stress results in altered structure-function, mitochondrial dynamics, and fibrosis in a G-protein dependent manner. Targeting G-protein signalling mediators might be a novel approach for attenuating the deleterious effects of chemotherapeutics and developing as adjuvant or improving existing treatment regimes for cardiac fibrosis. This concept will advance our understanding of the intricate cardiovascular physiology, regulation of cardiotoxicity with stress conditions, and underlying molecular mechanisms. The work described in this proposal is exiting, related to social problems, and of high clinical significance.

Co-PI:

Dr. Syed Masood Husain, Centre Of Biomedical Research, Delhi-226014, Dr. Sukhes Mukherjee, All India Institute Of Medical Sciences (AIIMS) Bhopal, Madhya Pradesh-462020

Total Budget (INR):

60,11,650

Organizations involved