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  •  Liver Systems Medicine Cancer - LiSyM-Cancer - is a systems medicine research network for the early detection and prevention of liver cancer. It is a multidisciplinary research network funded within the Federal Ministry of Education and Research program within the Framework of the National Decade Against Cancer. The aim of the joint project is to identify relevant biomarkers to diagnose and prevent hepatocellular carcinoma (HCC) at early stages. Ursula Klingmüller coordinates the subproject SMART-NAFLD and contributes to the subproject C-TIPP-HCC. SMART-NAFLD focuses on alterations in metabolism and signal transduction that favor disease progression to liver cancer. The project aims to identify alarm signatures in the blood of patients with fatty liver diseases without cirrhosis. This will facilitate to develop model-based trajectories for individual patients to evaluate the closeness to the tipping point towards liver cancer (tipping point 1). C-TIP-HCC employs mechanism-based multiscale modeling to address structural and compositional changes in the extracellular matrix, as well as differences in cellular phenotypes of hepatic stellate cells, hepatocytes and macrophages in cirrhotic nodules. This facilitates the discrimination of the tissue in compensated cirrhosis across a tipping point towards liver cancer formation (tipping point 2), and aims at predicting intervention strategies to slow down disease progression.       


  •  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 division of Ursula Klingmüller 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.     


  •  Based on an integrative analysis of high-quality mass spectrometric data, the MSCoreSys consortium SMART-CARE aims to identify molecular markers (proteins, metabolites) in tissue samples and body fluids (blood, CSF) that can be used for mathematical modeling to predict tumor recurrence in four important cancer types (blood, lung, brain, sarcoma). This will result in a stable MS-based workflow applicable in different clinical settings and will identify common as well as disease-specific indicators of tumor recurrence for personalized adjustment of treatment decisions.


  •  World-wide 109 million patients are suffering from anemia in the context of chronic kidney diseases (CKD). Patients suffering from anemia are treated with erythropoiesis stimulating agents (ESAs), which are derivatives of Epo. However, a too rapid increase in the number of red blood cells due to high ESA doses results in increased shear stress and thus a high risk of thrombovascular events such as thrombosis, heart attack or stroke.  The e:Med demonstrator project NephrESA employs a systems biology approach against renal anemia. NephrESA focuses on hemodynamics, inflammation, iron metabolism and platelet activation and utilizes patient data, patient samples and clinical conceptualization.  The results are integrated in a mathematical model and will be validated in the clinical routine of anemia treatment in CKD patients.


  •  Acute Myeloid Leukemia (AML) is a highly aggressive cancer with few treatment options for the majority of patients. The ERA PerMed transnational project AML_PM aims at improved treatments of acute myeloid leukemias by personalized medicine. Our multidisciplinary, translational approach with access to AML biobanks as well as longitudinal data from ongoing clinical trials provides in conjunction with data generated in the project a rich high-quality source for big data analytics and mathematical modelling. Dynamic pathway models are established to predict disease development and optimal treatment for individual patients that are tested in vitro and in vivo in pre-clinical models and by proof-of-concept validation in patients. The personalized medicine approach pursued in the project aims at validated bioinformatics and experimental pipelines for clinical decision-making and for tailoring treatment for individual AML patients.


DFG- funding

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

  • The CRC/Transregio 186, "Molecular Switches in the Spatio-temporal Control of Cellular Signal Transmission", focuses on the coordination processes in the transmission of signals in living cells that play a pivotal role in the functionality of biological systems. It remains largely unknown how activated molecular switches coordinate signal transduction in time and space. The research network is based on the development of a large number of chemical-biological tools that can be used for broad-based, direct manipulation of molecular switches. The division of Ursula Klingmüller in collaboration with Dorothea Fiedler (FMP Berlin) investigates molecular switches in the TGF-β signaling pathway and the role of inositol pyrophosphate messengers.


  • Iron deficiency and iron overload are both associated with bone loss and an increased risk of fracture, which markedly limit mobility and autonomy of affected individuals. Thus, iron levels must be balanced to maintain health in general, and in particular bone strength. The FerrOs consortium (FOR 5146) brings together experts of iron and bone metabolism to decipher the underlying mechanisms of iron regulation and its interactions with bone. The division of Ursula Klingmüller aims to unravel mechanisms regulating the dynamics of BMP signal transduction and its impact on the expression of the main iron regulator hepcidin with a systems biology approach.


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