Division of Functional Genome Analysis

Dr. Jörg D. Hoheisel

Visualisation of the degree of methylation in breast samples. Each sample is depicted as a coloured square and differentially methylated CpG sites are represented as black dots. All co-localise with the cancer samples at the right side, indicating that the highest methylation level is found in cancer. In contrast, healthy samples are located to the left, in the opposite direction off the centroid, indicating the lowest level of methylation. Likewise, based on the localisation of normal-appearing tissues from cancer patients and samples of benign tumours along the horizontal axis (first principal component), it can be seen that an intermediate methylation load existed in these samples.
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Research at the Division of Functional Genome Analysis focuses on an assessment and description of the realization and regulation of cellular function from genetic information.

Analysis of tumor material is at the center of attention, with an emphasis on pancreatic cancer and personalized approaches. The effect of DNA sequence variations and the epigenetic modulation of the genome are studied. This is combined with measurements on variations in transcription factor binding and changes in transcript levels of coding and noncoding RNAs. Concomitantly, the actual protein expression is analyzed. Besides the creation of basic scientific knowledge, we aim at establishing means for early and non-invasive molecular diagnosis as a basis for accurate prognosis, reliable patient stratification, and a precise monitoring of treatment results. Another objective is the identification of new therapeutic approaches. Particularly for this, we complement molecular analyses with functional studies for the elucidation of relevant cellular mechanisms.

Technically, we pursue particularly developments in the field of proteome analysis. Analytical processes in this area are still inadequate for many, especially biomedical purposes. We have established affinity-based processes that permit a robustness and reproducibility that meet the requirements of clinical applications and are amendable to translation. One scientific aim is the identification of disease-specific protein isoforms. Structural variation is often an indicator for different functional activity. Also, measurements of protein interactions are performed, in particular for the identification of variations that occur at a personal level. A third activity is the creation of a map of the protein-mediated communication between the different cell types of the pancreatic tumor microenvironment.


FUTURE OUTLOOK

Another line of work aims at the fully synthetic, in vitro implementation of complex biological processes. We are motivated to use them for the production of biomedically active molecules, such as non-immunogenic agents, and the establishment of an entirely artificial molecular system. Cell-free biosynthetic production will be crucial for mastering many biotechnological and pharmacochemical challenges. Artificial biological systems will complement Systems Biology by evaluating biological models experimentally. Similar to physics, insight into cellular function will be gained by an iterative process of performing experimental and theoretical Systems Biology. Eventually, this may lead to the establishment of a fully synthetic self-replicating system and, ultimately, an archetypical model of a cell.

Website of the Division

Contact

Dr. Jörg D. Hoheisel
Functional Genome Analysis (B070)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4680

Selected Publications

  • Botla, S.K. et al. (2016). Early epigenetic down-regulation of microRNA-192 expression promotes pancreatic cancer progression. Cancer Res., in press.
  • Bradbury, A. et al. (2015). Reproducibility: Standardize antibodies used in research. Nature, 518(7537), 27-29.
  • Moskalev, E.A. et al. (2015). GHSR DNA hypermethylation is a common epigenetic alteration of high diagnostic value in a broad spectrum of cancers. Oncotarget, 6(6), 4418-4427.
  • Nijaguna, M.B. et al. (2015). Definition of a serum marker panel for glioblastoma discrimination and identification of Interleukin 1? in the microglial secretome as a novel mediator of endothelial cell survival induced by C-Reactive Protein. J. Proteomics, 128, 251-261.
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