Research Focus and Main research questions
We focus on understanding the basic cellular pathomechanisms underlying cardiac diseases, with special attention on cardiac arrhythmias. In particular, we are interested in cyclic nucleotides signaling in human myocytes and how the remodeling on cAMP/cGMP-dependent kinases (such as PKA, and CaMKII via Epac) signaling is linked to compartment-specific changes in Ca2+-handling. Although many studies have been performed in animal models, the role of cyclic nucleotides, PKA, CaMKII and PDEs in human remains rather unexplored and controversial. We developed a novel isolation method, which allows us to culture human myocytes, to: 1) perform in classical electrophysiological and novel imaging techniques, 2) generate with knock-in /-out models directly in human cells, as new alternative method to animal testing and highly translational model for heart diseases.
- Role of PDE8 in cAMP dynamics and Ca2+-handling in atrial fibrillation
- Epac microdomain regulation of Ca2+-handling via cAMP and CaMKII in atrial fibrillation
- Regional specific remodeling of cGMP pathway in human atrial fibrillation
Our aim is to clarify how specific molecular alterations in cardiac cells and disease-related remodeling cause electrical instability and generate arrhythmias and to apply this knowledge to develop new mechanism-based and patient-tailored therapeutic strategies. Furthermore, our group has the overall responsibility for the translation to human of the animal studies performed at the Institute of Experimental Cardiovascular Research.