Epigenetic changes occur in various biological processes such as differentiation, development, senescence, stress response and transformation. De-regulations of these processes are closely linked to monogenic and complex diseases. Cancer, for example, is no longer regarded as a genetic disease in which genetic defects such as mutations and copy number variations influence gene regulation and ultimately lead to abnormal cell function (Timmermann B. et al. 2010; Schweiger M. et al. 2011). In fact, it has been shown that epigenetic changes represent another level of (de)regulation of gene activity (Schweiger M. et al. 2013; Peifer M. et al. 2015). Currently, DNA methylation is probably the best characterized epigenetic change, as high-throughput array and sequencing techniques provide epigenome-wide data that complement the available genomic and transcriptomic data (Boerno S. et al. 2010). Proper DNA methylation is required to ensure genome stability and correct lineage specification. In cancer genomes, for example, it has been found that cancer genomes are generally hypomethylated. However, hypermethylation is found at certain sites, especially at promoters. Hypermethylation at the promoter of tumor suppressor genes leads to their inactivation and to tumor development. Hypomethylation, on the other hand, occurs predominantly at heterochromatic sites that lead to the transcription of a large number of non-coding RNAs (ncRNA). Thus, abnormal overexpression of pericentromeric satellite RNA (SATIII) along with decondensation and demethylation of pericentromeric DNA has been found in neuroblastoma, lung, pancreatic, kidney, colon and prostate cancers, as well as in several genetic diseases, including ICF syndrome and the premature aging syndrome Hutchinson-Gilford progeria. Recently, we have shown that SATIII RNA is not only more highly expressed in malignant tissues, but also correlates with and induces resistance to etoposide therapy (Hussong M. et al. 2017; Kanne J. et al. 2021). Etoposide is a topoisomerase inhibitor that is used as first-line chemotherapy for small cell lung cancer.  In the case of pericentromeric heterochromatin (PH), local transcripts even appear to be involved in the formation and maintenance of heterochromatin as well as genomic stability, and could thus represent a driving force in malignant transformation.

Our research aims to understand the causes and consequences of cancer epigenome deregulation and its impact on cellular homeostasis. We apply epigenomic, biochemical, molecular and cell biological technologies to gain insights into epigenetic changes and their potential consequences. In particular, we are investigating the relationship between stress, the epigenetic patterning process and the consequences for RNA splicing. With the knowledge gained, we aim to gain insights into oncogenic pathomechanisms and develop new ways to diagnose and predict the therapeutic response of tumors and to develop new therapeutic options.

Our work focuses on the field of translational epigenetics.

We aim to understand the epigenetic mechanisms of cancer development, progression and resistance to therapy. We are particularly interested in non-coding genomic regions and how they contribute to impaired stress responses. Based on our findings, we are developing new therapeutic strategies for targeted and easily modulated chemotherapies.