RNA Modifications in Direct Cardiac Reprogramming (2023)

Undergraduate: Christopher Nguyen

Faculty Advisor: Yifang Xie
Department: Pathology and Laboratory Medicine

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Heart disease is the leading cause of death within the United States, accounting for about 1 in 4 deaths annually. An adult mammalian heart has extremely limited regenerative capabilities, so when cardiomyocytes are lost due to myocardial infarction, they are replaced with non-contractile fibrotic scar tissue. This in turn can lead to chronic heart failure and death. One promising approach for cardiac regeneration is direct reprogramming, which converts fibroblasts into induced cardiomyocytes (iCMs) through overexpression of cardiac transcription factors. A better understanding of the molecular mechanisms underlying this process is necessary for future clinical applications. While the transcriptional and epigenetic regulation of direct reprogramming is well- studied, its post-transcriptional regulation, especially regarding mRNA modification changes, and the underlying regulatory mechanisms of direct reprogramming are largely unknown. This project seeks to better understand how mRNA modification changes affect direct cardiac reprogramming. Preliminary data found that knocking out Gene A, a m6A reader, led to increased direct reprogramming yield.

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