Project description
Exploring the role of cholangiocytes in liver disease
The rates of chronic liver diseases such as metabolic dysfunction associated steatotic liver disease (MASLD) and its severe form, metabolic dysfunction associated steatohepatatis (MASH), are rising rapidly, yet lack effective treatments. While cholangiocytes (the cells lining the biliary tree) are key to bile drainage and liver regeneration, their role in disease progression and cancer remains underexplored. The ERC-funded FunChol project seeks to address this gap by combining cutting-edge research methods, including organoids, single cell analyses and preclinical models, to unravel how cholangiocytes drive tissue repair or exacerbate disease. Focusing on the mechanisms of cholangiocyte activation, plasticity and transformation, FunChol aims to uncover therapeutic targets to promote liver regeneration and combat disease progression, offering hope for treatments.
Objective
Cholangiocytes are the mCholangiocytes are the main cell type lining the epithelium of the biliary tree, a network of conduits which drain the liver from bile produced by hepatocytes. While the role of cholangiocytes have been broadly studied in the context of cholangiopathies, their role in chronic liver disease affecting hepatocytes is often overlooked despite growing evidence that they play a central role in disease progression, regeneration, and cancer. Thus, understanding the mechanisms controlling the regenerative potential of cholangiocytes is essential to develop new therapies promoting tissue repair or blocking tumour formation. However, the study of these mechanisms has been restricted by technical and conceptual barriers especially in human.
Here, we propose to bypass these limitations by developing an innovative program of research combining functional experiments in organoids, single cell analyses on human primary tissue and preclinical studies in animal models. We will use this approach to specifically address the role of cholangiocytes in chronic liver disease. More precisely, we aim to uncover the mechanisms driving cholangiocytes activation, plasticity and transformation. Importantly, we hypothesise that these different processes are interlinked and share common factors. The FunChol program will systematically address these questions in the context of Non-Alcoholic Fatty Liver Disease (NAFLD). This chronic disease and its progressive form Non-alcoholic Steatohepatitis (NASH) represent the most rapidly rising cause of liver cirrhosis worldwide and there is currently no therapy for this major health care challenge.
Overall, this multidisciplinary proposal will reveal the molecular interplays by which liver injuries can affect cholangiocytes and how in turn cholangiocytes react to improve tissue repair or to aggravate disease. This research will pave the way for the development of new therapeutics controlling regeneration to limit disease progression.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine hepatology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-ADG
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10117 Berlin
Germany
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