Department of Molecular Biology

Research Interests

Gene regulation. Our main research interest is directed toward understanding molecular mechanisms, by which intracellular signalling elicits differential genomic responses at the level of transcription. Primarily, we are interested in gene expression under the control of the transcription factor SRF (Serum Response Factor). This transcription factor controls target gene expression by recruiting to its DNA binding sites (CArG boxes) different SRF co-factors, which by themselves are subject to regulation by intracellular signalling cascades.The most important families of SRF co-factors are the TCFs (ternary complex factors) and the Myocardin/MRTF proteins. Whereas the former are under control of mitogenic MAPK signalling, the latter respond to Rho-mediated dynamical changes in the actin cytoskeleton. The TCFs belong to the Ets family of proto-oncoproteins.

SRF as experimental oncogene in hepatocellular carcinoma (HCC). We have generated SRF-VP16iHep mice, a genetic mouse model for HCC. This model is based on liver-specific mosaic activity of the constitutively active SRF fusion variant SRF-VP16. Using a multi-omics approach, which includes exome-seq, RNA-seq, sRNA-seq, proteomics, phospho-proteomics and metabolomics, we are trying to characterize the molecular mechanisms that contribute to HCC formation in the SRF-VP16iHep mouse model.

Non-coding mutations in human cancer genomes. In the field of human cancer genomics, recent interest has focussed on recurrent non-coding mutation (NonCoMs) that have been found in gene regulatory elements (promoters, enhancers). As coordinating member of the DKTK consortium "Noncoding mutations in cancer genomes", we search for new mutations in control regions of cancer-associated genes. Different tumor entities are being investigated, including melanoma and glioblastoma. Identified novel NonCoMs are being subjected to functional characterization in order to understand their relevances to human cancer pathology.

Molecular basis of endothelial cell aging: relevance to stroke. Based on our findings of endothelial SRF depletion causing cerebral hemorrhages, we are investigation the possibility that impaired SRF activity might lead to small vessel disease and stroke-like symptoms. This might be associated with age-dependent decline in the expression of SRF target genes. We are thus investigating age-dependent epigenetic mechanisms that impact on SRF activity in endothelial cells of the murine brain.