Projects
General aspects of Natural Killer cell biology
Project leader: Thorsten Lieke
Natural Killer (NK) cells are part of the innate immunity. They exhibit cytotoxic activity but can respond with cytokine release to certain trigger. The most outstanding characteristic is the fast induction of NK cell response. Inflammatory cytokines can be detected hours after protozoan parasites infection directing the adaptive immune response to a powerful reaction against the infection. On the other hand, NK cells reveal regulatory function during priming of T cells. This regulative capacity is restricted only to a subset of NK cells. In this regard, we evaluate and characterise interplay of NK cells with T cells and other cell population as well as a detailed investigation of the subset of regulatory NK cells. In addition, we are interested in mechanisms of NK cell activation in human, mouse and rats.
Interaction of T cells with tumor cells
Project leader: Thorsten Lieke
Tumor cells provoke innate and adaptive immune responses. For some tumors, inflammatory reaction support malignant outcome, some are controlled by the immune system. As a matter of fact not only the quantity and pathway of infiltration and response is crucial for successful combat of cancer but also the location of infiltrating lymphocytes in the tumor microenvironment. However, tumor cells established strategies for evasion of immune responses. We found a mechanism of contact dependent interaction of human and murine T cells with tumor cells leading to surprising consequences for both partners. We evaluate the nature of contact formation between T cells and tumor cells. Furthermore, we work on the outcome for T cell function and tumor viability.
Hepatocyte Transplantation
Project leader: Florian Vondran
Scientific staff: Wiebke Brauns, Nina Dobbernack , Ingrid Meder, Thorsten Lieke
Hepatocyte transplantation (HCTx) is a promising therapy option for the treatment of numerous inborn and acquired liver diseases. HCTx is much more cost efficient and a less invasive procedure than conventional liver transplantation (LTx). Furthermore, the method of cell transplantation enables the opportunity of pre-Tx modification of hepatocytes by technologies such as gene therapy. Unfortunately, the promising results obtained in animal models could not be successfully transferred into clinical application in man, yet. The aim of our project is to evaluate the immunological aspects of HCTx in order to establish new strategies for efficient cell transplantation with optimized long-term outcome.
Isolation, Culture and Cryopreservation of Primary Human Hepatocytes
Project leader: Moritz Kleine / Florian Vondran
Scientific staff: Wiebke Brauns, Ingrid Meder, Marc Riemer
Large quantities of primary human hepatocytes (PHH) are required for basic research and clinical applications. In addition, they represent a valuable tool used in pharmacotoxicology. In conclusion, the demands for PHH continuously increase while their supply is insufficient due to limited cell sources. The aim of our project is to evaluate alternative sources of liver tissue for the isolation of high quality primary human hepatocytes. Furthermore, we are interested in innovative concepts for long-term cell culture and cryopreservation of PHH in order to optimize the supply with liver cells for further use in vitro and in vivo.
The heme oxygenase-1 system in biliary tract disorders
Project leader: Johannes Klose / Michael Winkler
Heme oxygenase-1 (HO-1) is the rate limiting enzyme catabolyzing free, toxic heme into its three endproducts, namely carbon monoxide, biliverdin and free iron. HO-1 is strongly inducible and upregulated in numerous pathological conditions and by various stimuli, such as oxidative stress, inflammation or hypoxia. Due to its anti-apoptotic, anti-oxidative and anti-inflammatory properties HO-1 plays a central role in endogenous protection and maintenance of cellular homeostasis. Interestingly, HO-1 is upregulated in various types of cancer, although the exact meaning is still unkown. Our interest is to characterize the role of HO-1 in biliary tract diseases, including both inflammatory and malignant conditions, such as primary sclerosing cholangitis and cholangiocarcinoma. The exact pathobiology of biliary tract diseases in general is still poorly understood. More insights are essential to define new therapeutic strategies. Our aim is to elucidate the potential role of HO-1 as a target protein in the therapy of biliary tract diseases.
Cholangiocarcinoma – a black box in modern medicine
Project leader: Johannes Klose / Thorsten Lieke
Cholangiocarcinoma (CC) is a highly malignant primary liver cancer arising from the intra- or extra-hepatic bile duct. Prognosis is poor due to limited treatment options and advanced disease at presentation. Consequently, new approaches for the treatment of CC are urgent. Thus, the purpose of this project is to improve the current therapeutic strategies and to develop innovative treatment options for CC. This includes gaining more information about the pathobiology of CC, to identify new molecular targets, to asses new drugs and their effectiveness on CC and to develop and to establish a malignant cell line derived from primary biliary epithelial cells of the rat.