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EpiLIVER

Characterization and implications of DNA damage response in liver cancer

Total Cost €

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EC-Contrib. €

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Partnership

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Project "EpiLIVER" data sheet

The following table provides information about the project.

Coordinator
KOBENHAVNS UNIVERSITET 

Organization address
address: NORREGADE 10
city: KOBENHAVN
postcode: 1165
website: www.ku.dk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Denmark [DK]
 Project website http://www.bric.ku.dk/Research/andersen-group/
 Total cost 200˙194 €
 EC max contribution 200˙194 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2018-01-14

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KOBENHAVNS UNIVERSITET DK (KOBENHAVN) coordinator 200˙194.00

Map

 Project objective

Cholangiocarcinoma (CCA) is a devastating type of liver cancer that presents late, is difficult to diagnose and associated with a high mortality. Although worldwide the epidemiological trend is mixed, in the EU it has been steadily increasing for the last decade. Treatment is limited to tumor resection, which is not applicable in the vast majority of cases. The lack of any approved chemotherapy-based treatment is partially due to the poor understanding of the molecular mechanisms involved in the response to these drugs. Taking advantage of the comprehensive panel of established and primary CCA cell lines in the host PI’s lab and my expertise on the DNA damage response (DDR) and repair field, my proposal offers a new approach in this scenario by characterizing the DDR of CCA cells. This study will be focused on the DDR-related chromatin remodeling SWI/SNF complex. In recent works, mutations in this family of proteins were identified in 47% of all CCA cases analyzed through whole exome sequencing, hence providing a relevant rationale in studying this complex. First, I will identify candidate markers of all known components of the SWI/SNF complex, based on RNAi high-throughput analysis. I will then perform direct and quantitative measurements of the DNA repair activity in CCA cells, specifically related to homologous recombination repair (HR) by rapid and sensitive reporter assays. And lastly, I will determine the proteome dynamics in the CCA context. There are two exclusive novelties on this approach: (1) the described novel methods will be employed in the Hepatology field for the first time; and (2) the use of primary CCA cells will enable me to directly compare observations in culture with clinical outcome. This proposal will not only contribute to the understanding of a limited understood area in liver cancer, but also holds great promises for future clinical use, where DDR-based drugs are the clinical mainstay

 Publications

year authors and title journal last update
List of publications.
2017 Douglas V.N.P. Oliveira, Shanshan Zhang, Xin Chen, Diego F. Calvisi, Jesper B. Andersen
Molecular profiling of intrahepatic cholangiocarcinoma: the search for new therapeutic targets
published pages: 349-356, ISSN: 1747-4124, DOI: 10.1080/17474124.2017.1292127
Expert Review of Gastroenterology & Hepatology 11/4 2019-06-18
2017 Chirag Nepal, Colm J. O\'Rourke, Douglas VNP Oliveira, Andrzej Taranta, Steven Shema, Prson Gautam, Julien Calderaro, Andrew Barbour, Chiara Raggi, Krister Wennerberg, Xin W. Wang, Anja Lautem, Lewis R. Roberts, Jesper B. Andersen
Genomic Perturbations Reveal Distinct Regulatory Networks in Intrahepatic Cholangiocarcinoma
published pages: , ISSN: 0270-9139, DOI: 10.1002/hep.29764
Hepatology 2019-06-18

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