The heart is a complex organ comprising a broad spectrum of specialized cardiovascular cell types that work closely together to ensure proper cardiac function. Spatiotemporal and cell-type-specific gene expression patterns are controlled by non-coding cis regulatory elements in the genome such as enhancers and promoters. These regions and their activation state are characterized by distinct combinations of epigenetic modifications including histone modifications and DNA methylation. ​​

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Mutations in transcription factors and chromatin regulators can result in CVD and the majority of genetic variants associated with risk of CVDs are overlapping regulatory elements in the non-coding parts of the genome. CVDs are associated with structural remodelling, extensive transcriptional adaptations as well as changes in enhancer activity and histone modification profiles. However, despite progress in recent years the detailed transcriptional and epigenetic mechanisms underlying CVDs remain to be defined.

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Atrial Fibrillation and Heart Failure

We are particularly interested to reveal the detailed cell-type-specific epigenetic, gene regulatory and transcriptional changes underlying disease pathogenesis of two common cardiovascular diseases, atrial fibrillation and heart failure with reduced ejection fraction.  

​Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Current treatment options for AF show limited efficacy in maintaining sinus rhythm or are not suitable in all patients and 1 on 4 patients will progress from paroxysmal, intermittent AF to permanent AF within 5 years.

​Heart failure with reduced ejection fraction (HFrEF) affects more than 10 Million people wordwide. Pharmacological therapy reduces morbidity and mortality of heart failure, but no current therapy specifically targets the heart muscle and a transplant is the only cure. Mechanical unloading in patients with end-stage heart failure leads in some patients to improved heart function and partial remission of heart failure. 

​Congenital Heart Disease

We are very interested to understand the molecular underpinnings of congenital heart diseases (CHD). CHD represent the number one birth defects with a prevalence of ~0.8 % and improved survival of CHD patients has resulted in a growing adult CHD patient population. Proper cardiac development and heart function rely on the precise spatiotemporal control of gene expression. De novo mutations are often found in coding regions of transcription factors and histone modifying enzymes and a large fraction of genetic variants overlaps non-coding regulatory elements of the genome. 

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Part of this line of research is a subproject of DFG-funded GRK 2344: MeInBio and supported by the DFG-funded CRC1425 Heterocellular Nature of Cardiac Lesions: Identities, Interactions, Implications.