The general goal of our research is to unravel the molecular mechanisms of the progression of chronic liver disease as basis for innovative diagnostic and therapeutic approaches.
The focus lies on hepatic fibrosis and hepatocellular cancer but we expand our studies to development and progression of fibrosis and cancer in other organs as in the skin or the intestine.
In this project, which is funded by the German Research Association (DFG), we investigate the role of Fibroblast Growth Factors (FGFs) in the development and progression of liver fibrosis. The focus lies on Fibroblast Growth Factor 7 (FGF7) also called Keratinocyte Growth Factor (KGF) and its receptor Fibroblast Growth Factor Receptor 2 IIIb (FGFR2IIIb).
In collaboration with Prof. Anja Bosserhoff we have discovered and characterized MIA2 as novel gene of the MIA gene family. MIA2 is exclusively expressed by hepatocytes.
Interestingly, hepatic MIA2 expression correlates significantly with the stage of hepatic fibrosis in patients with different kinds of underlying liver disease.
In a research consortium we are developing an ELISA for the quantification of the protein MIA2 in the serum of patients together with our academic Partner Prof. Anja Bosserhoff and our industrial Partner Scil Proteins.
The project is funded by the German Ministry for Education and Research (BMBF) within the framework Molecular Diagnostics.
Well characterized cry-banks of different specimens from patients with various liver diseases are the basis for the identification of genetic risk factors and diagnostic markers for the progression of chronic liver diseases.
Also together with collaboration partners we are searching for markers that predict the progression of hepatic fibrosis and the development and progression of hepatocellular carcinoma.
Further, we established in vitro systems with parenchymal and non-parenchymal liver cells isolated from different human donors to assess and simulate, respectively, variations in the development of fibrosis or the progression of hepatocellular cancer as observed in different patients. These analysis are performed in close collaboration with the Center for Liver cell Research at the University Hospital Regensburg and the Human Tissue and Cell Research (HTCR) Foundation.
Cells isolated under standardized conditions from different donors were compared in functional assays and regarding the activation of pathophysiologically relevant signaling pathways and the expression of critical genes.
Further, the effect of conditioned medium collected from activated hepatic stellate cells isolated from different donors on HCC target cells from one single donor are being compared.
In more complex approaches target cells from different donors or co-culture experiments are used.
The focus of these studies lies on Xanthohumol, the principle prenylchalcone of the hop plant Humulus lupulus L, and they are funded by the Barth-Haas Group.
We have already shown that Xanthohumol inhibits hepatic inflammation and fibrosis as well as the tumorigenicity of HCC cells. Currently, we are working on the identification of the underlying mechanisms of these hepatoprotective effects. Further, we study the metabolisms as well as the bioavailability of Xanthohumol, which are widely unknown.
In addition to Xanthohumol we expand our research to other hop constituents as bitter acids, and pharmacologically effective compounds of other plants as in Salix and Arnica on basic mechanisms of wound healing and fibrosis.