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Epigenetic and Genetic interplay in Liver Cancer

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.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Net EU contribution

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.

€ 202 125,12
Address
Chariteplatz 1
10117 Berlin
Germany

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Region
Berlin Berlin Berlin
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

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