Rudiger von Harsdorf

Degrees:MD

Positions:
Senior Scientist Division of Experimental Therapeutics Toronto General Research Institute (TGRI)

Research:
Regulation of replicative capacity of cardiomyocytes: Our studies focus on the role of cell cycle inhibitors (including p21CIP1 and p27KIP1) and cell cycle activators (including members of the E2F transcription factor family) in the maintenance and control of cardiomyocyte cell cycle arrest. According to our studies p21CIP1 appears to play a crucial role in the early phase of cell cycle control in cardiac muscle cells by controlling PCNA expression. We also found that in contrast to most other mammalian cell types in cardiomyocytes, the transcriptional activity of E2F1 is regulated in an pRB-independent manner. Regulation of cell death in cardiomyocytes: Initiation of cell cycle activity in terminally differentiated cardiomyocytes is inevitably counter-acted by robust induction of apoptosis. This may be the underlying nature of the lack of any true cardiac tumors in the heart (myxomas are not of cardiomyocyte origin). Thus, in order to coax cardiomyocytes back into the cell cycle, apoptosis has to be kept in check in order to allow significant cardiac regeneration. Identification and employment of constitutively active and tissue-specifically expressed antiapoptotic factors is required. A molecule which seems to fulfill these requirements is ARC. We performed an in depth-analysis of ARC regulation in cardiamyocytes. Moreover, our group generated an ARC-deficient mouse model. ARC deficiency leads to enhanced cardiac failure in biomechanical and ischemic cardiac stress models. Regulation of cardiomyocyte hypertrophic growth: Cell cycle inhibitors as well as cell cycle activators not only control cell cycle activity in cardiomyocytes, they also play a crucial role in hypertrophic growth in these cells. We are trying to understand the regulation and effect of cell cycle factors in the context of hypertrophic growth. Additional Appointments Robert McEwen Chair in Cardiac Regenerative Medicine Full Staff Member in Interventional Cardiology at Toronto General Hospital Associate Professor in the Department of Medicine at the University of Toronto