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CholangioConcept SIGNED

Functional in vivo analysis of cholangiocarcinoma development, progression and metastasis.

Total Cost €

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EC-Contrib. €

0

Partnership

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 CholangioConcept project word cloud

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

liver    cancer    therapies    gut    inevitably    metabolism    identification    urgently    aggressive    cholangiocarcinoma    ccc    heterogeneity    advantage    lifestyle    solid    therapy    adult    functionally    diagnosis    poorly    emphasis    mechanisms    time    innovative    envision    primary    dissect    duct    drugs    profiling    metastatic    data    chimaeric    discussed    hallmarks    employ    vulnerabilities    emerged    screening    bile    unclear    mouse    oncogenomic    shrna    becomes    icc    incidence    models    complexity    translational    western    treatment    irresectable    insights    strategies    resistance    direct    develops    frequent    functional    harbor    surgical    exists    option    cytotoxic    tumors    microbiome    curative    vivo    resection    characterization    regimen    altered    clear    mosaic    erc    stable    therapeutic    hepatic    metastasis    kras    driving    ing    molecular    tumor    rates    sharply    hepatocytes    yield    systemic    progression    expertises    cholangiocarcinogenesis    influences    genetic    health    intrahepatic   

Project "CholangioConcept" data sheet

The following table provides information about the project.

Coordinator
EBERHARD KARLS UNIVERSITAET TUEBINGEN 

Organization address
address: GESCHWISTER-SCHOLL-PLATZ
city: TUEBINGEN
postcode: 72074
website: www.uni-tuebingen.de

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 Germany [DE]
 Total cost 1˙998˙898 €
 EC max contribution 1˙998˙898 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EBERHARD KARLS UNIVERSITAET TUEBINGEN DE (TUEBINGEN) coordinator 1˙998˙898.00

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 Project objective

Genetic heterogeneity and complexity are hallmarks of metastatic solid tumors and therapy resistance inevitably develops upon treatment with cytotoxic drugs or molecular targeted therapies. Cholangiocarcinoma (CCC, or bile duct cancer) represents the second most frequent primary liver tumor and has emerged as a health problem with sharply increasing incidence rates, in particular of intrahepatic CCC (ICC). The reason for increased CCC incidence remains unclear, but influences of western lifestyle and a resulting altered hepatic metabolism have been discussed. Surgical resection represents the only curative option for the treatment of CCC, however, many tumors are irresectable at the time of diagnosis. CCC represents a highly aggressive and metastatic tumor type and currently no effective systemic therapy regimen exists. The overall molecular mechanisms driving CCC formation and progression remain poorly characterized and it thus becomes clear that a detailed molecular characterization of cholangiocarcinogenesis and the identification of robust therapeutic targets for CCC treatment are urgently needed. Taking advantage of our strong expertises in chimaeric (mosaic) liver cancer mouse models and stable in vivo shRNA technology, we here propose a comprehensive and innovative approach to i) dissect molecular mechanisms of cholangiocarcinogenesis, with a particular emphasis on Kras driven ICC development from adult hepatocytes and oncogenomic profiling of ICC metastasis, ii) to employ direct in vivo shRNA screening to functionally identify new therapeutic targets for CCC treatment and iii) to characterize the role of the gut microbiome for CCC progression and metastasis. We envision this ERC-funded project will yield important new insights into the molecular mechanisms of CCC development, progression and metastasis. As our work comprises direct and functional strategies to identify new vulnerabilities in CCC, the obtained data harbor a very high translational potential.

 Publications

year authors and title journal last update
List of publications.
2018 Marco Seehawer, Florian Heinzmann, Luana D’Artista, Jule Harbig, Pierre-François Roux, Lisa Hoenicke, Hien Dang, Sabrina Klotz, Lucas Robinson, Grégory Doré, Nir Rozenblum, Tae-Won Kang, Rishabh Chawla, Thorsten Buch, Mihael Vucur, Mareike Roth, Johannes Zuber, Tom Luedde, Bence Sipos, Thomas Longerich, Mathias Heikenwälder, Xin Wei Wang, Oliver Bischof, Lars Zender
Necroptosis microenvironment directs lineage commitment in liver cancer
published pages: 69-75, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0519-y
Nature 562/7725 2019-04-18
2018 Laura Faletti, Lukas Peintner, Simon Neumann, Sandra Sandler, Thomas Grabinger, Sabine Mac Nelly, Irmgard Merfort, Chun-Hao Huang, Darjus Tschaharganeh, Tae-Won Kang, Florian Heinzmann, Luana D’Artista, Ulrich Maurer, Thomas Brunner, Scott Lowe, Lars Zender, Christoph Borner
TNFα sensitizes hepatocytes to FasL-induced apoptosis by NFκB-mediated Fas upregulation
published pages: n/a, ISSN: 2041-4889, DOI: 10.1038/s41419-018-0935-9
Cell Death & Disease 9/9 2019-04-18

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