Cardiogenetics (RG Hoffmann)

Research Group

Annette Löwen (MTA); Kristin Rädecke (PhD student); Ambuj Gore (MSc student); Sandra Hoffmann (Group Leader) (from left to right)

Research Focus

The heart’s rhythm is initiated and regulated by a population of specialized cells in the sinoatrial node, the natural pacemaker of the heart. Cardiac arrhythmias are pathological abnormalities from the normal heartbeat and are among the most common heart diseases.

In the last few years, transcription factors and their targets have been shown to play important roles in the pathophysiology of atrial fibrillation, the most common cardiac arrhythmia, indicating that dysregulated gene expression is an essential underlying mechanism. Yet, our knowledge on gene regulatory networks associated with atrial fibrillation remains limited. Based on previous analysis, we have established a functional link between the expression of the homeodomain transcription factor SHOX2, the development of the sinoatrial node and arrhythmogenic phenotypes including atrial fibrillation and sinus node dysfunction.

Since the risk for atrial arrhythmias is defined by genetic alterations, we are highly interested in elucidating the underlying genetic networks and processes using state-of-the-art methods. We are applying different model systems and technologies including animal models (transgenic mice, zebrafish), patient material and pluripotent stem cells (patient-specific iPSCs, mouse ESCs) combined with cellular and molecular biological approaches, genome-editing (CRISPR-Cas9), genomic, transcriptomic and epigenomic tools.

Modelling atrial arrhythmias with genotype-guided approaches using iPSCs will improve our understanding of the molecular mechanisms by which genomic variation cause those diseases. Moreover, these approaches provide a preclinical model for the selection of novel therapeutic targets, paving the way to personalized medicine.

Group Leader