Biology

Dr. Saher Mehdi
KU Leuven, Leuven, Belgium

To meet the increasing demands of the body for blood supply as it grows from birth to adult and following physical training or pregnancy, the heart muscle grows. This growth happens through enlargement of the muscle cells (hypertrophy) not an increase in their number (proliferation). The heart muscle also grows when it is damaged (it cannot repair itself) following an infarction or after prolonged hypertension. Growth during pathology is not beneficial and often leads to heart failure. We have studied how these different forms of cardiac remodeling occur and why cardiomyocytes don't divide to repair the damaged heart. We have found substantial differences in the patterns of genes that are altered during the different forms of hypertrophy. An important way by which genes are switched on and off is by epigenetic modification of the DNA. There are different epigenetic modifications that switch on and off genes. Using high throughput sequencing approaches, we have identified a particular epigenetic mark that controls the gene expression pattern associated with disease but not during physiology, and its loss makes heart cells more like those in the neonate. We have also identified how this mark is altered in the heart. The aim of my current research is to understand how this epigenetic regulator is controlled, how it acts to only regulate cardiac remodeling and whether it can control both myocyte cell division and growth. This work may contribute to better strategies for cardiac regeneration and repair.