Systems Biology of Signal Transduction

Division of Systems Biology of Signal Transduction

Prof. Dr. Ursula Klingmüller

In erythroid progenitor cells the cell membrane is visualized by staining for transferrin receptor expression (green) and the nucleus by staining for DNA content (blue)
© dkfz.de

The goal of the division is to gain insights into molecular mechanisms that regulate cellular decisions, and to address their impact on behavior at the tissue and organ level. When these control mechanisms fail, cancer and other diseases arise. Cellular responses are regulated by a multitude of extracellular signals received by cell surface receptors. Within cells the information is processed through complex intracellular signaling networks that in turn impinge on gene regulation and affect metabolism to finally coordinate physiological responses such as proliferation, survival and differentiation. These responses operate on very different time scales, ranging from minutes to hours and days. Thus, it is essential to examine key dynamic properties of biological systems, which can be addressed by combining the generation of quantitative time-resolved data with mathematical modeling. Data-based mathematical models enable rapid testing of hypotheses to uncover deregulation in cancer and to predict strategies of intervention in diseases. In close collaboration with modeling partners, methods for quantitative analysis of signaling networks were developed and multiple dynamic pathway models were established, yielding unexpected insights into regulatory mechanisms of signaling pathways. The main projects of the division address:

  1. Unraveling principal mechanisms of erythropoietin (Epo)-mediated cellular decisions in the hematopoietic system.
  2. Bridging from the cellular to the whole organ level during liver regeneration.
  3. Attaining insights into altered regulation in cancer and prediction of strategies for efficient intervention in diseases (cancer, drug-induced liver injury, viral infection).
  4. Contribution to personalized treatment options in lung cancer

FUTURE OUTLOOK
This knowledge will be used to establish integrated models of signaling pathways, to link them to gene regulation as well as cell-cell communication and to include cell cycle progression and cell survival. Finally, we aspire to integrate this information into multi-scale models and whole body models. Translational aspects are strengthened through intensive collaborations with clinical partners and companies in the frame of large third-party funded research networks.

Contact

Prof. Dr. Ursula Klingmüller
Systems Biology of Signal Transduction (B200)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4481

Selected Publications

  • Becker V. et al. (2010). Covering a broad dynamic range: information processing at the erythropoietin receptor. Science, 328(5984): 1404–1408.
  • Raia V. et al. (2011). Dynamic mathematical modeling of IL13-induced signaling in Hodgkin and primary mediastinal B-cell lymphoma allows prediction of therapeutic targets. Cancer Res, 71(3), 693–704.
  • Bachmann J. et al. (2011). Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range. Mol Syst Biol, 7: 516.
  • Mueller S. et al., (2015) T160-phosphorylated CDK2 defines threshold for HGF-dependent proliferation in primary hepatocytes. Mol Syst Biol, 11(3): 795.
to top