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Systems Biology of Signal Transduction

Division of Systems Biology of Signal Transduction

Prof. Dr. Ursula Klingmüller


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 have been 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 and gaining insights into mechanisms contributing to liver damage in response to drugs or viral infection.
  3. Attaining insights into altered regulation in cancer and prediction of strategies for efficient intervention in erythroleukemia, liver cancer and lung cancer.
  4. Contribution to personalized treatment options in lung cancer.
This knowledge will be used to establish integrated models that link signal transduction to gene expression and metabolism and include the impact on cell cycle progression and cell survival as well as cell-cell communication. These integrative models are essential building blocks for the establishment of mechanistic multi-scale models that allow quantitative predictions of the consequences of alterations at the cellular scale for the entire organ. Finally, through the link of the integrative models with pharmacokinetic models we closely collaborate with clinical partners and companies in the frame of large third-party funded research networks to propose optimized treatment options for individual patients and thereby contribute to personalized medicine.


Prof. Dr. Ursula Klingmüller
Systems Biology of Signal Transduction (B200)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg

Selected Publications

  • Becker V. et al. (2010). Covering a broad dynamic range: information processing at the erythropoietin receptor. Science, 328(5984): 1404–1408.
  • Marwitz, S., et al. (2016), Downregulation of the TGF-ß pseudoreceptor BAMBI in non-small cell lung cancer enhances TGF-ß signaling and invasion. Cancer Res., 76(13):3785-3801.
  • Adlung, L., et al. (2017), Protein abundance of AKT and ERK pathway components governs cell-type-specific regulation of proliferation. Molecular Systems Biology, 13(1):904.
  • Lucarelli et al., (2018), Resolving the the Combinatorial Complexity of Smad Protein Complex Formation and Its Link to Gene Expression Cell Systems 6, 1-15
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