Research Projects

Cardiovascular diseases are a major cause of mortality globally and in India, and there is a need to identify novel drug targets. Heart failure is primarily caused by factors such as myocardial infarction, aging, hypertension, aortic stenosis, infection, obesity, genetic predisposition, cardiotoxicity, and cancer-induced cachexia. Cardiac cachexia, characterized by a loss in cardiac mass due to ongoing cardiomyocyte apoptosis and atrophy, is a major cause of heart failure. Despite its prevalence, its molecular mechanisms and druggable targets remain poorly explored. One potential target is YTHDF3, an RNA-binding protein with a YTH domain that plays a critical role in cardiac health. The researchers aim to uncover the cardiac function of YTHDF3 by cardiomyocyte-specific knockdown in mice. Preliminary data shows that AAV9-mediated YTHDF3 knockdown leads to cardiomyocyte apoptosis and atrophy, leading to impaired cardiac function. The researchers hypothesize that cardiomyocyte-specific knockdown will also lead to cardiac apoptosis, atrophy, and impaired function. They also explore YTHDF3's role in cardiac alternative splicing and nuclear mRNA export.