AG Bartenschlager
Prof. Dr. Ralf Bartenschlager
Research Projects
Virus infections of the liver are of high medical relevance, because they are often associated with serious liver damage, including liver cirrhosis and hepatocellular carcinoma (HCC). Up to now, 5 viruses with an exclusive hepatotropism have been identified, which are therefore called hepatitis viruses. Of these the hepatitis B virus (HBV), the hepatitis D virus (HDV) and the hepatitis C virus (HCV) are most relevant because of their capability to establish persistent infection and their global prevalence. WHO estimates that ~70 million people are chronically infected with HCV and ~240 million with HBV. In addition, an estimated 10-20% of chronic HBV carriers are co-infected with HDV, which is a satellite virus requiring HBV as helper virus. Although infections with these viruses most often are asymptomatic, persistently infected individuals have a high risk to develop serious liver disease. The molecular mechanism underlying development of liver cirrhosis and HCC are poorly understood. It is widely believed that the immune response induced by viral infection triggers chronic inflammation. This immune response is unable to eliminate the virus, but causes cell damage and death, thus creating space in the liver for compensatory cell proliferation. During these cell divisions, mutations can occur with their generation being enhanced by the chronic inflammatory milieu. In addition, HBV and HCV induce multiple perturbations in infected cells, contributing most likely to tumor formation. Additional, tumor-promoting factors are the metabolic syndrome, high body-mass index and consumption of cytotoxic agents such as alcohol or DNA-damaging substances such as aflatoxins contained in contaminated food.
Given the complexities of external cues, understanding liver tumor formation requires an interdisciplinary research approach, combining expertise in virology, cell biology and immunology. We employ state-of-the-art cell culture models, cutting-edge imaging methods, including correlative microscopy and cryo-EM, genome-wide phenotypic screening and multi-omics approaches. Our goal is to decipher the mechanisms driving hepatitis virus-associated liver cancer with the aim to identify novel targets of use for the development of prophylactic and therapeutic treatment modalities.
Apart from that, in the course of the COVID-19 pandemic, we established a research network called CoViPa that aims to decipher the virological and immunological determinants of COVID-19 pathogenesis and to use gained knowledge to get better prepared for future pandemics.
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