Hepatology Research Unit: Projects

Biobank

The lab collects biospecimens in a biobank for biomedical research purposes, including:

    • genomic DNA
    • serum

Fundamental Research

Angiogenesis, ER stress and chemoresistance through PlGF inhibition in a mouse model of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer worldwide (564,000 cases/year) and the third most common cause of cancer mortality. At diagnosis, most patients with HCC are ineligible for curative surgery and can only be offered palliative treatment. Systemic therapy with classical cytotoxic drugs yields low objective response rates without proven survival benefit. Recently, the multikinase inhibitor sorafenib demonstrated a limited survival advantage for patients with advanced HCC. Sorafenib is an oral drug which blocks PDGF-, VEGF-, c-Kit- and raf signaling, both on the tumor cell and the surrounding endothelial cells. Consequently, other drugs need to be developed and novel strategies with complementary mechanisms are required to maximize efficacy and minimize resistance to current therapy with angiogenesis inhibitors or cytotoxic drugs.
Endoplasmic reticulum (ER) stress, which can be induced by intratumoral hypoxia, is present in HCC and could play an essential role in tumor growth and metastasis. Therefore, we investigate the therapeutic potential of agents modulating the ER stress pathways and angiogenesis in HCC.

Endoplasmic Reticulum stress in liver disease

Endoplasmic Reticulum stress is involved in the pathogenesis of many different diseases among which (chronic) liver diseases. Targeting ER stress and the unfolded protein response pathways could offer therapeutic possibilities. Tauroursodeoxycholic acid (TUDCA) has been shown to reduce ER stress and has been tested in a variety of liver disease models. A link between ER stress and angiogenesis has also been observed in different disease models and is further explored in chronic liver diseases.

The role of hypoxia on liver progenitor cells in primary liver cancer

The major primary liver cancers in adults are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). These tumours outgrow their vascular supply and become hypoxic. We have shown a possible link between hypoxia in the tumor environment and the differentiation of liver progenitor cells (LPC), holding great potential for therapeutic intervention. Hypoxic conditions in the HCC environment could trigger LPC to differentiate towards a cholangiocytic phenotype, which has a more aggressive phenotype. Furthermore, hypoxic conditions created by anti-angiogenic therapy, like sorafinib, may adversely select for more invasive tumor variants better adapted to survive and proliferate under reduced oxygen tension. This project will bring new insights to the effect of hypoxia on the differentiation of LPCs in the development of primary liver tumours.

Glycomics in chronic liver diseases and solid organ transplantation

The last decade, it has become clear that protein glycosylation (glycomics) plays a major role in chronic liver diseases. This knowledge has led to the development of several biomarkers for liver cirrhosis, liver fibrosis, non-alcoholic steatohepatitis and hepatocellular carcinoma. Major steps in this field have been achieved in close collaboration with Prof. Dr. Nico Callewaert from the Unit for Molecular Glycobiology from the Flanders Institute for Biotechnology (VIB). Our focuses on the role of glycomics in solid organ transplantation, mainly in liver transplantation. The final goal of this research project is to study the potential  of glycomics as biomarkers for complications after solid organ transplantation.