Project description
Epigenome regulators in intrahepatic cholangiocarcinoma
Intrahepatic cholangiocarcinoma (iCC) is an aggressive cancer of the biliary tract with patient survival less than one year after diagnosis. Genomic analyses have identified mutations in epigenetic regulators associated with iCC. The EU-funded EPiCC project proposes to use patient-derived cell lines to characterise the functional role of key epigenetic regulators and the modifications linked to iCC chemotherapy resistance to identify new therapeutic targets. The specific aims of the project are the identification of iCC-associated functional epigenetic modifications using CRISPR/Cas9 technology and the characterisation of the epigenomic changes induced by the loss of the epigenetic regulators.
Objective
Intrahepatic cholangiocarcinoma (iCC) is an aggressive malignancy of the biliary tract with escalating rates among both sexes in EU. Patients survive less than one year from diagnosis due to limited treatments and innate chemoresistance. Genomic analyses have identified recurrent mutations in epigenetic regulators in iCC. Malfunction of such genes has genome-wide consequences for epigenome-remodeling and transcriptome homeostasis, though this remains largely uncharacterized in iCC. Further, the extent to which iCC survival depends on these epigenetic alterations has not been determined. Clarification of these dependencies on epigenetic alterations, which unlike mutations are reversible, is crucial for the development of precision epigenome-targeted therapies for this aggressive disease. Using patient-derived cell lines (PDCLs), I propose to characterize iCC epigenetic survival dependencies to define the functional role(s) of key epigenetic regulators and ensuant epigenome remodeling, in turn identifying putative novel therapeutic targets. To achieve this, I have divided my EPiCC proposal in 2 specific aims:
1.Identify iCC-selective functional survival dependencies by state-of-the-art CRISPR/Cas9 screening.
2.Characterize the anti-neoplastic cellular and (epi)genomic consequences induced by the top epigenome regulator loss.
Through integrating novel comprehensive approaches in iCC (CRISPR/Cas9 screening, R-loop mapping) with robust patient models (primary cells, omics from patient samples), I will provide novel insight into the epigenetic landscape of iCC and identify potential targets for future development of epigenetic-based precision medicine. This study will be supervised by Dr. Andersen, leading expert in the field of hepatobiliary cancers and translational genomics research. Therefore, EPiCC will provide me with new scientific expertise (both technical and transferable skills), a broader network and open new research avenues to follow up in my 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.
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- medical and health sciences health sciences personalized medicine
- natural sciences biological sciences genetics epigenetics epigenomes
- medical and health sciences basic medicine physiology homeostasis
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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)
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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
1165 KOBENHAVN
Denmark
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.