About UsThe cardiac Wnt-complex in the developing, healthy and diseased heart
Heart failure is characterized by an imbalanced myocardial damage and repair. Understanding the mechanisms causing progressive
damage and halting repair will be the basis to develop new therapeutic concepts for preventing heart failure progression. Based on
several data indicating that modulation of Wnt/β-catenin signaling may be instrumental in cardiac function preservation and
regenerative strategies, we aim to unravel Wnt-dependent factors and mechanisms instructing cardiac tissue formation, heart homeostasis
and remodeling in a cell specific manner.
Our main current topics include:
(I) Krueppel-like factor (KLF) 15-Wnt dynamics in homeostasis and remodeling of the mouse and human myocardial tissue;
(II) the role of Wnt-related factors for endothelial cell homeostasis of the fetal and diseased heart;
(III) the epigenetic role of TCF7L2 on Wnt/β-catenin mediated activation in the regenerative and diseased heart;
(IV) the Wnt-exosome mediated signaling in the adult heart and its cellular cross-talk;
(V) the role of novel cardiac Wnt components in cardiogenesis and,
(VI) the characterization of cardiomyocytes secreted protein in heart failure.
This knowledge will contribute to the understanding of cardiac specific Wnt-dependent mechanisms essential for heart homeostasis with special emphasis of mechanisms conserved in human tissue.
β-catenin/TCF7L2 transcriptional activation induces TCF7L2 and H3K27ac recruitment to disease-associated enhancers and results in increased developmental processes, cardiomyocytes cell cycling and cytoskeletal remodeling in the adult heart. doi: 10.1093/nar/gky049
Our methodology is based on biochemical, epigenetic, transcriptional and functional investigation of novel identified factors using classical mouse knockout strategies combined with embryo culture and tissue explants as well as CRISPR/Cas9-based technology for gene targeting (knockout and gene activation) in vitro in human stem cells and in vivo in the mouse
Mouse embryo (day 9.5) cultured after electroporation with a GFP expressing plasmid into the developing heart tube.