Project: The function of inflammatory signalling pathways and micro RNAs in acute liver disease, liver fibrosis and liver cancer

Most chronic liver diseases are not sufficiently treatable at present and very often progress to liver cirrhosis and hepatocellular carcinoma (HCC). Whereas eradicating the primary cause of HCC, e.g. chronic viral hepatitis, is currently unattainable, our goal is the identification and molecular characterization of central molecular mechanisms and inflammatory signalling pathways that play a role in the mediation of liver injury, liver cirrhosis and ultimately liver cancer which might be the basis for the future development of novel drugs. Our lab focuses on the following three aspects of liver research, featuring both basic science projects in genetically modified mice and cell culture as well as more clinically oriented projects in patient cohorts treated at our clinic. In all three topics we have currently free positions for medical students that want to do their medical thesis as well as for biologists/biological chemists (Master, Thesis, Post Doc). We are collaborating with several groups in the US and Europe.

Topic 1: The role of inflammatory signalling pathways in hepatocarcinogenesis.

We have generated several conditional knockout mice for central molecules that mediate the communication between extracellular inflammatory messengers (cytokines, chemokines) as well as inflammatory cells (Lymphocytes, monocytes, NK cells etc.) to transcriptional programmes and basic cellular processes in parenchymal liver cells (immune responses, proliferation, cell death, malignant transformation). We are using immunological and cell biological technologies such as FACS, cell sorting, Electro-Mobility-Shift-Assays, Western Blots etc. to study the role of these molecules in mouse models and primary cell culture systems.

Topic 2: The role of miRNAs in models of hepatic disease.

We have recently started to study the role of the newly discovered microRNAs, small non-coding RNAs that play a role in the repression of gene transcription/translation. As such, we could show a new molecular role of the microRNA-29 family in the mediation of liver fibrosis. Moreover, we are studying the role of microRNA in the development of liver cancer.

Topic 3: MicroRNAs as novel biomarkers in patients with gastrointestinal cancer.

In these more clinical projects, we are evaluating the potential of measuring microRNA-levels in the serum of patients with cancer in the GI-Tract (colon-cancer, liver cancer, pancreas cancer, stomach cancer). We want to find out, if they can be used in future to detect cancer at an early stage or to predict treatment responses and outcome in patients undergoing surgery or chemotherapy. This project is an interdisciplinary study together with the department of surgery.