Epigenetische Regulatie van de Cardiomyocytcelcyclus

This Ph.D. project is built upon the recently published findings from Thienpont, Aronsen, Robinson et al. (JCI 2017) and will contribute to the development of new strategies for enhancing cardiac regeneration and ameliorate disease. The role of the epigenome in determining and maintaining the post-mitotic adult cardiac myocyte phenotype remains to be fully explored and it is important to examine how the epigenome itself can be manipulated to enhance regeneration and ameliorate disease. Considering that the adult myocyte is characterized by an absence of proliferation, it is intriguing and clinically relevant to identify exactly how the cardiac myocyte fate can be reprogrammed so that the inadequate proliferation would be reversed, thereby enabling the repair of the damaged heart. Moreover, the absence of proliferation in the adult heart provides an ideal substrate to examine epigenetic mechanisms independent of cell cycle. The aim of this project is to probe the role of histone methylation in the regulation of cardiac proliferation and in preventing/reversing harmful hypertrophic remodelling. This research will test the notion that the manipulation of histone methylation can be used as a tool to reprogram cardiac myocyte phenotype, and enhance proliferation required for repair.