Project H: Life and death in the chronically injured liver

Department of Gastroenterology and Hepatology
Coordinators:  Prof H Moshage PhD, Prof KN Faber PhD

Type of research: Basal, laboratory
Field: Hepatology, Cell Biology

Background
Chronic liver diseases are characterized by the progressive loss of hepatocytes, the functional liver cells, as a result of cell death. Several toxic factors present in the chronically injured liver contribute to cell death, e.g. reactive oxygen species, pro-apoptotic cytokines like TNF and bile acids. Cell death is the consequence of either necrosis (or passive cell death) or apoptosis (programmed cell destruction).  In contrast to necrosis, apoptosis is an active and strongly regulated process and therefore amenable to intervention. At the same time, during chronic liver diseases, there is proliferation of connective tissue cells in the liver, the so-called stellate cells. This proliferation and activation of stellate cells leads to liver fibrosis.

To treat the detrimental effects of chronic liver diseases, i.e. death of hepatocytes and proliferation of stellate cells, we need to know the exact actions of toxic factors, present during liver diseases, on hepatocytes and stellate cells.

Goals of our studies are
1) to elucidate the effects of relevant toxic factors present in the chronically injured liver
2) to determine the mechanism of cell death induced by these factors
3) to prevent cell death induced by these factors by manipulating signal transduction pathways

Approach
The research of the department is very much focused on laboratory work. It involves both in vivo and in vitro (cultured hepatocytes and stellate cells). The student participates actively in the research of the department and will be supervised by PhD students/technicians and Amster students of the department. In our lab two former ISCOMS attendants are active as researcher. Techniques used will include: hepatocyte/stellate cell isolation and culture, assays for apoptosis (caspase activity, nuclear condensation), intervention in intracellular apoptosis and signal-transduction pathways, assays for cell proliferation, mRNA isolation and real time PCR, Western blotting and immunofluorescence microscopy.