Research

Current Projects

CRIS database

Inge Mannaerts "Liver Fibrosis reversal through hepatic stellate cell inactivation"
 

As hepatic stellate cells are the main scar producing cells during liver fibrosis, they are also the most obvious cell type for therapeutic intervention. Despite many years of research, fibrosis remains an incurable disease and novel approaches are therefore required. We aim at better understanding the activation of hepatic stellate cells, but also to understand a newer aspect of stellate cell biology e.g. the inactivation of stellate cells. We hypothesize that promoting inactivation might enhance fibrosis regression. In our project we will address mechanisms intrinsic to stellate cell (in-)activation and it’s regulation by the neighbouring endothelial cells and kupffer cells. For these studies we use well established mouse models of fibrosis but we also develop complex in vitro cultures, combining stellate cells with hepatocytes, endothelial cells and kupffer cells.

 

Stefaan Verhulst Update soon (Crowd: "How soon?" - His Majesty: "Véry soon!")
   

 

Liza Dewyse "Liver disease in microfluidic organotypic systems"
collagen One major obstacle in the development of efficient therapies for chronic liver disease, such as liver fibrosis and NAFLD, is the lack of robust and representative in vitro models, as these often fail to mimic the complex 3D structures and cellular organisation found in vivo. During my PhD project, we aim to develop biomimetic in vitro models of liver disease, which will serve to a better understanding of liver disease and will allow us to target and better understand the early initiating events and the dynamic progression of liver fibrosis leading to cirrhosis. Therefore, we make use of liver-representative microtissues, namely mouse- or human-derived organoids and precision cut liver slices, cultured in microfluidic systems, which subsequently will be used to mimic liver fibrosis/chronic liver disease, to investigate associated mechanisms and pathways.

 

Joeri Lambrecht "Staging of liver fibrosis by hepatic stellate cell specific biomarkers"
 

In the current clinical setting, the most specific and sensitive diagnostic tool for liver fibrosis, remains the liver biopsy, an invasive procedure associated with multiple drawbacks. Although the development of multiple non-invasive means, based on serological circulating factors and/or elastographic quantifications, high diagnostic value for the identification of all stages of the liver fibrosis process is still lacking. My PhD project proposes the use of circulating extracellular vesicles, small membrane-derived structures with endocytic origin, as a novel diagnostic tool for the identification of onset and progression of liver fibrosis.  As such extracellular vesicles are shed by almost all cells in the body, and have a heterogenous content consisting of proteins, small non-coding RNAs, lipids, etc, and depending on their cell-origin, we hypothesize their potential use as indicative tool for liver homeogenesis, and thus disease progression.

 

Vincent De Smet "Tackling liver fibrosis by targeting hepatic stellate cell inactivation"
  Liver fibrosis, cirrhosis and cancer are an increasing problem worldwide with a substantial global burden of disease. Liver fibrosis consists of a pathological deposition of extra-cellular matrix, which is produced by hepatic stellate cells who activate upon liver damage. When the liver injury is stopped, reversal of fibrosis is accompanied by inactivation of the HSCs. However, there is only limited knowledge on the mechanisms behind HSC inactivation. My PhD project focusses on sinusoidal cell communication to discover novel mechanisms of fibrosis development and reversal both in mice and human. Novel information gained from my PhD will fuel new treatment strategies for liver fibrosis.

 

Lianne Van Os "The role of liver sinusoidal endothelial cells in chronic liver disease"
  Liver sinusoidal endothelial cells (LSECs) are the most permeable cells of the body and very important for liver function. During chronic liver disease and fibrosis these highly specialized endothelial cells are not able to maintain their specific phenotype and lose their important characteristics. Together with our EU consortium DeLIVER we hope to unravel more about the dynamic liver sinusoidal endothelial cells in both health and disease. During my PhD project we want to establish a 3D in vitro model with hepatocytes, hepatic stellate cells and liver endothelial cells. In addition, we will look at different chronic disease models in mice to both study LSEC morphology and their role in chronic liver disease in vivo and in vitro.

Finalized projects

HILIM 3D: Humanized Immune Liver Mouse and 3D in vitro models for the study and therapy of liver disease (IWT-SBO programme 11/2014-10/2018)

Biomarkers for liver fibrosis risk assessment (FWO-V 2017)

Hepatic 3D co-culture system for the evaluation of (anti-)fibrotic compounds (IWT 2014-2017)

HEPRO II: Human liver disease: study of the hepatic stem cells and their niche, and development of novel model systems (IAP VII programme 10/2012-09/2017)

A phase I study on the feasibility and safety of mRNA immunotherapy in combination with RFA in patients with hepatocellular carcinoma (UZ Brussel W.Gepts Foundation 2013 + 2015-2016)

Liver progenitor cells, their secretome and liver regeneration (IWT 2013-2016)

Modulation of liver fibrosis by liposome-mediated selective targeting of hepatic stellate cells (IWT 2013-2016)

The link between hypoxia and progenitor cells during liver carcinogenesis (FWO-V 2013-2016)

Extensive characterization of different human liver progenitor cell populations (FWO-V 2013-2016)

Generation, Isolation and Expansion of Human Quiescent Hepatic Stellate Cells (IWT 2012-2015)

Role of ER stress in angiogenesis associated liver cirrhosis and portal hypertension (FWO-V 2012-2015)

HEMIBIO:  Hepatic Microfluidic Bioreactor (EU-FP7 programme 2011-2015)

Interplay between epigenetic modification mechanisms and microRNAs (VUB GOA 2011-2015)

A 3D tissue culture model for screening of anti-fibrotic compounds (UZ Brussel W.Gepts Foundation 2015)

The Role of Autophagy in Liver Fibrosis (IWT 2011-2014)

BRUSTEM I & II: Regenerative medicine of the liver using synergistic mixtures of immature or mature human hepatocytes with mesenchymal stem / progenitor cells or with hepatic stellate cells (Brussels Government - Innoviris (impuls programme Life Sciences 06/2008-05/2011 + renewal 06/2011-05/2014))

HEPSTEM: Functional human hepatocytes, stellate cells and sinusoidal endothelial cells generated from stem cells (IWT-SBO 11/2009-10/2013)

Analysis of HDAC repressor complexes with a function during liver fibrosis (FWO-V 2009-2012)

Role of angiogenesis and angiogenetic factors (VEGF, PLGF) in portal hypertension and fibrosis formation in animal models of cirrhosis, steatosis and portal hypertension (FWO-V 2009-2012)

HEPRO: The hepatic progenitor cell niche under experimental conditions and in human liver disease (IAP VI programme 2007-2011)

Liver fibrosis as a target for non viral gene therapy (FWO-V 2009)

Biology and pathobiology of the liver progenitor cell niche (FWO-V 2008-2011)

Role of specific histon deacetylases during liver stellate cell activation and fibrogenesis  (IWT 2007-2010)

Epigenetic modification of gene expression by interference with histone acetylation (VUB GOA 2006-2010)

HEPADIP: Hepatic and adipose tissue and functions in the metabolic syndrome (EU-FP6 programmme 11/2005-10/2010)

Stem cell niches in liver and pituitary : interactions between progenitors, their committed progeny, niche cells and the extracellular matrix (FWO-V equipment grant for FACSAria Cell Sorter - 2006-2009)

Role of dystrophin-associated protein complex in contraction of hepatic stellate cells (FWO-V 2006-2009)

Analysis of a transcriptional repressor complex and its function during cell type specification and differentiation (FWO-V 2008)

 

Partners and networks

Tools & Assays

update soon