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EpiLIVER

Characterization and implications of DNA damage response in liver cancer

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

EpiLIVER project word cloud

Explore the words cloud of the EpiLIVER project. It provides you a very rough idea of what is the project "EpiLIVER" about.

reporter liver mutations homologous swi primary repair panel mortality offers culture mixed hence compare majority works trend direct lack steadily context decade observations remodeling snf treatment scenario assays mainstay perform recombination quantitative holds cholangiocarcinoma epidemiological lastly rapid time chemotherapy rnai first molecular 47 last advantage components area vast hepatology poor clinical difficult host markers devastating diagnose cell exclusive throughput resection rationale cells damage drugs ddr dna expertise exome applicable worldwide me pi limited proteins family dynamics mechanisms employed hr lines sequencing candidate proteome chromatin sensitive approved cca tumor novelties lab characterizing promises cancer outcome

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 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.	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

List of publications.
year	authors and title	journal	last update
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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