DNA Repair and Epigenomics
Overview
Effective DNA repair requires a loosening of the chromatin structure and is closely linked to epigenetic changes at damage sites. In addition, there is increasing evidence on important interactions between DNA damage response and the immune response.
© Ali Bakr
Basic events in tumorigenesis include the loss of genomic integrity and, more and more important, massive alterations of the epigenome like DNA methylation, histone marks and non-coding RNAs. Multiple mechanisms have been developed to maintain stability of both genome and epigenome despite of the permanent threat by endogenous and exogenous factors. Silencing of DNA repair genes by epigenetic promoter methylation is just one important example how epigenetically altered targets affect tumor development as well as tumor therapy.
Our research interest is aimed to understand the impact and maintenance of the epigenome by analyzing the methylome, histone marks and further epigenetic regulatory mechanisms in exposed cells and in various diseases. Methods include
- genome-wide and locus-specific DNA methylation and chromatin analyses,
- investigation of gene expression by exploring epigenetic control of regulatory sites like promoters and enhancers, as well as
- functional analyses of DNA damage response such as cell survival and repair.
In close cooperation with clinical partners, we focus our research on common cancer types like colorectal, pancreatic and head and neck cancer, but also on therapy outcome or the incidence of treatment-related side effects. These translational projects will improve prognosis and treatment outcome of cancer patients.
Present Research Projects aim
- to apply genome-wide DNA methylation profiling to explore intra-tumor heterogeneity and the protective role of estrogen signaling in colorectal cancer
- to investigate genome-wide epigenetic regulation of enhancers in tumor development
- to elucidate interactions of DNA damage and repair mechanisms (e.g. induced by ionizing radiation) with DNA methylating and demethylating pathways resulting in altered epigenetic gene regulation
- to identify epigenetically induced functional deficiencies in DNA damage response and to elucidate their impact on individual cancer risk, radiosensitivity, therapy outcome and prognosis
- to identify the impact of differentially methylated regions on the incidence of radiation-induced fibrosis in breast cancer patients.