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  • The German Center for Lung Research (DZL) is one of the biggest European consortia dedicated to lung research. It creates a unique framework for close cooperation between basic research scientists and clinicians to uncover the underlying mechanisms and develop new diagnostic and treatment options for severe lung diseases such as lung cancer, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, end-stage lung disease, acute lung injury, and pulmonary hypertension. The Klingmüller group contributes to the disease area lung cancer and uses a Systems Biology approach to identify markers for early detection and to elucidate mechanisms contributing to tumor progression and therapy resistance.



  • ERA-Net for Systems Biology Applications (ERASysApp): IMOMESIC (Integrating Modelling of Metabolism and Signalling towards an Application in Liver Cancer). Uncontrolled proliferation in cancer results from synergistic adaptations in metabolism and signaling. However, coupling mechanisms between metabolism and signaling are difficult to assess. As a proof of concept, we focus on liver cancer, and propose a combined experimental and modelling approach that exploits both comprehensive genome-scale models to identify global, cancer-specific alterations and a more detailed integrative model that links glycolysis and signaling. The proposed framework will act as a show case for Systems Biology approaches to integrate metabolism and signaling in oncology and will open new avenues for the treatment of liver cancer. The Klingmüller group focuses on the quantitative analysis of the link between growth factor signaling and metabolism.



  • e:Bio - Modull-II : MS_DILI (Multi-Skalen Modellierung der Medikamenteninduzierten Leberschädigung). To establish a highly innovative Systems Biology pipeline to examine mechanisms contributing to drug induced liver injury (DILI), we focus our multi-scale approach on DILI induced by Paracetamol (Acetaminophen, APAP). The Klingmüller group performs time- and dose-resolved measurements on the impact of APAP on the dynamics of pro-inflammatory (IL-6, TNF-alpha) and growth factor (HGF, EGF, TGF-beta)-induced signaling in hepatocytes. In addition, we monitor in primary mouse hepatocytes on the population by mass spectrometry as well as at the single cell level by time-resolved live cell imaging the effect of APAP on cellular responses, such as cell death and cell proliferation. The work will contribute to the development of a biotechnological software tool to aid the safety assessment of drugs causing DILI. The overall aim is to identify a biomarker set for patient stratification according to their risk to develop DILI.



  • LiSyM (Liver Systems Medicine) represents a research network of German centers and institutions, in which mathematicians, modelers, pharmacologists, molecular biologists and clinical scientists work together to develop a Systems Medicine approach to study early and advanced liver disease. The aim of this unique research program is to acquire and use new experimental data and data from existing data bases to build computational models that facilitate decision making at the patient's bedside and to predict the actions of new medicines in the treatment of metabolic liver disease. The Klingmüller group contributes to the elucidation of mechanisms promoting liver fibrosis and of acute-on-chronic liver failure.



DFG- funding

  • The CRC/Transregio TRR179 examines “Determinants and dynamics of elimination versus persistence of hepatitis virus infection”. The Klingmüller group addresses strategies to harness an effective antiviral response targeting hepatitis B virus. Chronic infection with hepatitis B virus (HBV) remains a major health burden. Since the outcome of an infection is determined by multiple non-linear interactions, we will use a Systems Biology approach to identify rate-limiting steps determining the outcome of the HBV infection and to elucidate mechanisms that could be exploited to strengthen the Interferon-induced antiviral response with the aim to prevent chronicity of the HBV infection


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