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Project
Creation of a dynamic intercellular liver communication platform to establish an anti-fibrotic combo-therapy for chronic liver diseases. (FWOTM989)
Liver disease causes 2 million deaths per year worldwide, among 1
million due to complications of cirrhosis, an advanced stage of liver
fibrosis. Key players in this process are hepatic stellate cells (HSCs).
During any type of liver injury, HSCs activate and produce excessive
extracellular matrix increasing the stiffness of the liver. To date, there
are no efficient anti-fibrotic therapies and therapies are often focused
on only one single target. Potential anti-fibrotic therapies that inhibits
HSC activation or promote the healthy state of HSCs are limited. This
project proposes to create a dynamic intercellular liver
communication platform, based on the expanding amount of single
cell RNA sequencing data, to identify new potential targets that can
be combined to treat chronic liver diseases.
The focus of this project
are signals that can affect healthy or activated HSCs. These novel
targets will be investigated in a combo-therapeutic approach using
several novel in vitro fibrosis models and in NAFLD-, cholestasis and
toxic injury-mediated mouse models of chronic liver disease. The
expected outcome will be the identification of new targets that, when
treated simultaneously, could inhibit chronic liver disease in human
and a dynamic publicly available web-based liver cell interaction
platform for fellow scientist to discover.
million due to complications of cirrhosis, an advanced stage of liver
fibrosis. Key players in this process are hepatic stellate cells (HSCs).
During any type of liver injury, HSCs activate and produce excessive
extracellular matrix increasing the stiffness of the liver. To date, there
are no efficient anti-fibrotic therapies and therapies are often focused
on only one single target. Potential anti-fibrotic therapies that inhibits
HSC activation or promote the healthy state of HSCs are limited. This
project proposes to create a dynamic intercellular liver
communication platform, based on the expanding amount of single
cell RNA sequencing data, to identify new potential targets that can
be combined to treat chronic liver diseases.
The focus of this project
are signals that can affect healthy or activated HSCs. These novel
targets will be investigated in a combo-therapeutic approach using
several novel in vitro fibrosis models and in NAFLD-, cholestasis and
toxic injury-mediated mouse models of chronic liver disease. The
expected outcome will be the identification of new targets that, when
treated simultaneously, could inhibit chronic liver disease in human
and a dynamic publicly available web-based liver cell interaction
platform for fellow scientist to discover.
Date:1 Nov 2020 → 31 Oct 2023
Keywords:Intercellular communication platform, Ligand-receptor interaction, Anti-fibrotic combo-therapy
Disciplines:Stem cell biology, Cellular interactions and extracellular matrix, Hepatology, Bioinformatics data integration and network biology, Analysis of next-generation sequence data