The main research focus of our group is to investigate mechanisms of transcriptional control in cardiovascular cells. The heart is a heterocellular organ that composes of multiple cell types, including cardiac myocytes, endothelial cells, fibroblasts, immune cells, and others, that take distinct roles in cardiovascular physiology and disease. We aim to understand which mechanisms determine chromatin remodeling, transcription factor activity, and gene expression in different cell types and thus control their biological function.
Pharmacology of the mineralocorticoid receptor
Mineralocorticoid receptor (MR) antagonists are a cornerstone of heart failure therapy. However, adverse effects related to concurrent MR inhibition in the kidney preclude the use of current MR antagonists in many patients. Therefore, novel approaches that specifically target the MR signalling pathway in the heart vs the kidney are needed. The mineralocorticoid receptor belongs to the family of ligand-activated transcription factors und elicits most of its activities through regulation of gene expression. We could show that the mineralocorticoid receptor mediates distinct effects in different cell types such as cardiac myocytes or endothelial cells that contribute to the pathophysiology of heart disease.
The goal of our research is to understand the molecular function of MR in different cell types and to identify epigenetic mechanisms or co-regulatory factors that might serve as organ-selective targets within the MR signaling pathway.
Epigenetic regulation of endothelial cell biology
Endothelial cells constitute a large proportion of non-myocyte cells in the heart and are today considered to be key regulators in the cardiovascular system. They contribute to all major cardiovascular diseases, from atherosclerosis to coronary artery disease and heart failure. In previous studies, we could show that the cardiac endothelial cell transcriptome is highly cell type- but as well organ-specific, reflecting the distinct biological function of endothelial cells in different organs.
We aim to elucidate how epigenetic mechanisms determine cell type-specific gene expression and function of cardiac endothelial cells and to evaluate their potential as new biomarkers or therapeutic targets.
- in vivo studies (echocardiography, RV/LV pressure catheterization, ECG/blood pressure telemetry)
- Cell/nuclei isolation (FACS, FANS, MACS)
- Gene expression & chromatin analysis (RNAseq, ATACseq, ChIPseq, Bioinformatics)