Karl-Dimiter Bissig Lab

Projects

Master
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Metabolic Liver Disease

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We establish novel xenograft models using human hepatocytes from metabolic liver disease patients. We have created the first xenograft model for metabolic liver disease using hepatocytes from a patient with familial hypercholesteremia. We are exploring new therapeutic approaches using CRISPR/Cas9 genome engineering strategies and establish new therapeutic concepts called “metabolic pathway reprogramming”.

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Liver Cancer

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Liver cancer is the third most common cause of cancer related death. We have established an orthotopic xenograft model for pediatric liver cancer of all histological subtypes including hepatocellular cancer. These patient-derived tumor xenografts recapitulated the genetic and biological characteristics—including the metastatic behavior—of the corresponding primary tumors. Furthermore, we derived two new pediatric cancer cell lines from the xenografted mice. Using these two new tools we performed a patient specific therapy and thereby demonstrated the utility of the novel xenograft model and cell lines.

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Hepatitis B Virus

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We explore new animal models and therapies for HBV. We use our human chimeric liver mice as one infection system to mimic authentic viral infection. In order to study immunocompetent mouse models, we have also developed a new transgenic HBV mouse line that can be used for studying therapies in clearance and drug testing. Finally, we have studied different treatment modalities, including gene editing, antisense strategies, and various immunotherapies for their efficacy in treating chronic HBV infection.

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Drug Metabolism

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Mice and humans differ significantly when it comes to drug metabolism. This limits accurate prediction of xenobiotic metabolism. We are using humanized mice to accurately predict human drug metabolism and are exploring novel strategies to improve human specific drug metabolism.