Speaker 1: Dr. Matthijs Blankesteijn, Dept. of Pharmacology&Toxicology, CARIM, Maastricht University
Title of the talk: Interventions in WNT signaling stimulate cardiac regeneration
Short summary: Myocardial infarction (MI) is a common cardiovascular event, frequently causing heart failure. This is due to cardiomyocyte loss and replacement by scar tissue in the infarct area, resulting in excessive dilatation of the ventricles. During normal wound healing after MI, the low rate of proliferation of cardiomyocytes in adult mammals prevents regeneration of the lost cardiac tissue, shifting the balance towards a massive fibrotic response. Therefore, investigations aiming to redirect the wound healing process away from scar formation, into the direction of cardiac regeneration have high scientific and societal potential. Interestingly, complete regeneration of the heart after injury has been demonstrated in zebrafish and newborn mice, underscoring its potential. Previous research has shown that multiple signaling pathways, including WNT signaling, are associated with the induction of cardiac regeneration in zebrafish and new-born mice. In the meantime, a rapidly growing body of literature has been published, showing the beneficial effects of interventions in WNT signaling in infarct healing in adult mammals. In this presentation, I will discuss the different pathophysiological mechanisms involved in infarct healing and the potential effects of interventions in WNT signaling on them.
Speaker 2:Wulf Tonnus, MD, clinician scientist, University Hospital Dresden
Title of the talk: Drugging cell death to modulate inflammation
Short summary: Based in intensive care medicine, nephrology, and solid organ transplantation, Dr. Tonnus works on the delicate interplay of regulated cell death and inflammation. Whereas apoptosis was long seen as a synonym for regulated cell death, this nowadays encompasses various forms or regulated necrosis. Thus, necrosis became druggable raising new questions: Why so many pathways of regulated cell death? Why so complicated biochemistry to just get rid of a cell? Dr. Tonnus utilizes translational models of acute kidney injury to investigate the relative contribution of various forms of regulated necrosis such as necroptosis, ferroptosis, and pyroptosis and their inflammatory consequences. Whereas necroptosis and pyroptosis rely on enzymatic reactions to proceed, these are relatively easy to pharmacologically modulate. As ferroptosis relies on iron-dependent lipid peroxidation, this mode of cell death is particularly difficult to block in vivo. Here, Dr. Tonnus already demonstrated efficacy of different radical trapping agents in ameliorating acute kidney injury. Furthermore, he was involved in the development of the first combined inhibitor of both necroptosis and ferroptosis, Nec-1f. Dr. Tonnus aims to bring modulation of regulated cell death from bench to bedside.