Project description
Understanding liver cancer tumour development
Liver cancer represents a leading cause of mortality, yet little is known about its cellular origins. While the genetic triggers for liver cancer are well documented, the ways in which cancer-driver mutations and epigenetic erosion collaborate to promote cellular plasticity remain unexplored. Supported by the Marie Skłodowska-Curie Actions programme, the EpiGen-LC project will address this knowledge gap, aiming to identify foundational risk factors of liver cancer to guide the development of improved early detection strategies. Leveraging CRISPR techniques, it will insert cancer-driver mutations in organoids from healthy and damaged liver tissue to analyse how liver cancer-driver mutations promote epigenetic remodelling and cellular plasticity as well as how such epigenetic changes further amplify cancer-promoting activity.
Objective
Liver cancer is a leading cause of mortality worldwide, yet its cellular origins are poorly understood. The Valier lab (host) has shown that a population of hepatocyte-cholangiocyte bi-phenotypic cells expands during the progression of chronic liver disease (MASLD). Chronic injury leads to epigenetic erosion, which has been recognised as a cancer hallmark. Whilst genetic drivers of liver cancer have been identified, the capacity of epigenetic erosion and cancer-driver mutations to cooperate to drive cellular plasticity has not been explored. This fellowship will build on my expertise in somatic mutation acquisition in chronically inflamed tissues to: O1. Determine the capacity of liver cancer-driver mutations to promote epigenetic remodelling and cellular plasticity, and O2. Determine the capacity of epigenetic remodelling to drive cellular plasticity and enhance the function of liver cancer-driver mutations. The Vallier lab is uniquely positioned to host this project, having established protocols to derive and transdifferentiate human cholangiocyte and hepatocyte organoids. Using CRISPR, I will introduce cancer-driver mutations in organoids from healthy and epigenetically eroded end-stage liver disease tissue and evaluate the impact on plasticity between hepatocytes and cholangiocytes. This fellowship will give me expertise in liver biology, patient-derived organoids, genome engineering, epigenomic profiling, as well as bioinformatic skills. Communication and outreach will be supported by the international and translational environment of the BIH at Charité and the MPI-MG. I will acquire an interdisciplinary collaborative network and develop leadership skills under the mentorship of Prof. Dr. Vallier. By combining access to rare liver organoids with my background in mutation dynamics, the project will uncover early determinants of liver cancer that may inform strategies for early detection, and equip me to transition into an independent academic research career.
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 liver cancer
- social sciences sociology demography mortality
- natural sciences biological sciences genetics mutation
You need to log in or register to use this function
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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
See all projects funded under this callCoordinator
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
10117 Berlin
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.