[Translate to Deutsch:] Tumor Genomic

[Translate to Deutsch:] The major scope of our work relates to the molecular mechanisms of mature B-cell malignancies, namely chronic lymphocyitc leukemia and multiple myeloma. By using state-of-the-art molcular and computational methods, we like to unravel the interplay of somatic mutations with epigenetic changes and how these affect cellular phenotypes.

Our group is interested in the interplay between functional genomic elements and epigenetic features and how their interactions shape cellular identity. Disruption of the genomic context these interactions take place in can cause deregulation of the associated transcriptional programs thereby fueling cellular transformation, as happening in several hematopoetic cancers by translocations between highly active immuno-globulin genes and growth control loci. Given the fact that the human genome contains more regulatory than coding regions, additional non-coding aberrations presumably influence cellular growth control pathways and thereby change cellular fate.

Therefore, our research focuses on the characterization of regulatory sites and their  interactions with transcription factors and epigenetic modifiers. Understanding how pivotal regulatory circuits are maintained and how oncogenic driver events are generated by their disruption is a central goal of our work. Moreover, we explore the molecular consequences of deregulated genes as well as the mechanisms preserving epigenetic information.

Combining NGS-based methods with bioinformatic approaches, we aim to unravel the consequences of regulatory mutations, how they reshape the epigenetic landscape and alter 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.

Furthermore, by performing targeted RNA-sequencing we advance the characterization of  the cell lines in our collection. In order to provide data-based guidelines for the selection  of ideal model lines for individual types of cancer containing recurrent aberrations, we screen for a multitude of cancer-relevant genes, their expression and their mutational status as well as for putative gene-fusions.

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 intership- 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.