Functional Tumor Genomics

Our group is interested in the interplay between functional genomic elements and epigenetic features and how their interactions shape cellular identity. Mutations in or the disruption of regulatory sites, like enhancers or insulator sequences can cause deregulation of the associated transcriptional programs thereby fueling cellular transformation, if proto-oncogenes or tumor suppressors are affected (Fig. 1). 

Given the fact that the human genome contains more regulatory than coding regions, multiple non-coding aberrations presumably influence cellular growth control pathways and thereby change cellular fate. Understanding how pivotal regulatory circuits are maintained and how oncogenic driver events are generated by their disruption is a central goal of our work. Combining NGS-based methods with bioinformatic approaches, we aim to unravel the consequences of regulatory mutations, how they render the interactions of transcription factors and epigenetic modifiers, thereby reshaping the epigenetic landscape and altering transcriptional networks. Besides examining these effects in model systems closely resembling genomic aberrations found in cancer patients, we deploy genome editing to reconstruct particular events and follow their molecular effects (Fig. 2).

Furthermore, our group aims at the continuous molecular characterization of the cell lines in our collection. In order to provide data-based guidelines aiding the selection of ideal model lines for individual (sub-)types of cancer, we use different sequencing based approaches to examine the mutational status of relevant genes, their expression as well as putative fusion-events.

Opportunities to join: We frequently offer internship- and master-projects for motivated students, within our scientific scope.

Selected References

  1. The LL-100 panel: 100 cell lines for blood cancer studies. Quentmeier H, Pommerenke C, Dirks WG, Eberth S, Koeppel M, Nagel S, Steube K, Uphoff CC, Drexler HG; Sci Rep. 2019 Jun 3;9(1):8218.
  2. Helicobacter pylori infection causes characteristic DNA damage patterns in human cells. Koeppel M, Garcia-Alcalde F, Glowinski F, Schlaermann P and Meyer TF; Cell Rep: 2015 Jun 23;11(11):1703-13. 
  3. Crosstalk between c-Jun and TAp73α/β contributes to the apoptosis–survival balance. Koeppel M, van Heeringen SJ, Kramer D, Smeenk L, Janssen-Megens E, Hartmann M, Stunnenberg HG, and Lohrum M; Nucleic Acids Res. 2011: Aug;39(14):6069-85.