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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.

Non-alcoholic fatty liver disorder (NAFLD) and Liver Transplantation

Project leader: Ulf Kulik

Liver transplantation is the only promising treatment option for many end-stage liver diseases. Regarding the rising incidence of fatty liver degeneration in western populations and the decreasing number of human donors with acceptable liver grafts, the transplant evaluation of limited liver grafts with higher extent of fatty degeneration appears more and more likely. Thus, the aim of this project is to assess the reversibility of fatty liver degeneration after liver transplant in a rat model and gain understanding of the molecular mechanisms involved in this process. Furthermore therapeutic strategies to improve liver regeneration following liver transplant are investigated. The project is conducted in cooperation with the Institute for Toxicogenomic Research, Director: Prof. Dr. J. Borlak.