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Systems biology of liver cancer: an integrative genomic-epigenomic approach

Objective

Cancer is a complex disease involving multiple genetic and epigenetic events occurring, and influencing each other, over a long period of time. Understanding cancer, and ultimately developing effective targeted therapies, will therefore require that mutations and epigenetic alterations be systematically investigated during the multiple stages of disease development, from identifiable pre-neoplastic phases to overt cancer. Until now, no systematic effort has been undertaken to investigate these multiple layers of genome organization and function during cancer development. MODHEP aims at providing a 360° understanding of liver cancer, one of the most common types of tumors and, because of the homogeneity of the hepatic tissue, the most experimentally tractable one. The consortium brings together elite European scientists in the fields of genetics, chromatin regulation, genomics, liver cancer, computational and systems biology. This combination of skills will allow us to investigate and model at unprecedented resolution the chain of events leading from environmental perturbations and the occurrence of driver mutations to preneoplastic disease and cancer. Our experimental plan reflects some grounded assumptions: 1. cancer cannot be modeled without detailed information on the preneoplastic stages of disease; 2. genetic heterogeneity in humans would make systems-level modeling non realistic from a practical point of view. Both of these limitations are bypassed by the use of well-defined mouse models, followed by evaluation of the main conclusions in clinical samples; 3. many early stage driving events in cancer represent epigenetic alterations, which are invisible to classical genetic analysis, and are confounded by secondary and tertiary events in established tumors. Our approach will enable the identification of therapeutically relevant early-stage genetic and epigenetic alterations and the definition of their interplay in tumor development and maintenance.

Call for proposal

FP7-HEALTH-2010-two-stage
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Coordinator

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Address
Via Morego 30
16163 Genova
Italy

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Activity type
Research Organisations
Administrative Contact
Giulia Campodonico (Ms.)
EU contribution
€ 687 841,70

Participants (17)

INSTITUT CURIE
France
EU contribution
€ 1 362 500
Address
Rue D'ulm 26
75231 Paris

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Activity type
Research Organisations
Administrative Contact
Corinne Cumin (Ms.)
MEDICAL RESEARCH COUNCIL
United Kingdom
EU contribution
€ 11 903,99
Address
20 Park Crescent
W1B 1AL London

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Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Kate Wilson (Dr.)
KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Netherlands
EU contribution
€ 805 000
Address
Kloveniersburgwal 29 Het Trippenhuis
1011 JV Amsterdam

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Activity type
Other
Administrative Contact
Don Van Velzen (Mr.)
FONDAZIONE TELETHON ETS
Italy
EU contribution
€ 825 230,99
Address
Via Varese 16/b
00185 Roma

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Activity type
Research Organisations
Administrative Contact
Irene Mearelli (Dr.)
THE UNIVERSITY OF EDINBURGH
United Kingdom
EU contribution
€ 493 177
Address
Old College, South Bridge
EH8 9YL Edinburgh

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Isobel Blair (Ms.)
THE BABRAHAM INSTITUTE
United Kingdom
EU contribution
€ 797 486
Address
Babraham Hall
CB22 3AT Cambridge

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Activity type
Research Organisations
Administrative Contact
Caroline Edmonds (Dr.)
WEIZMANN INSTITUTE OF SCIENCE
Israel
EU contribution
€ 647 999
Address
Herzl Street 234
7610001 Rehovot

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Talia Tzahor (Ms.)
RIKEN THE INSTITUTE OF PHYSICAL ANDCHEMICAL RESEARCH
Japan
EU contribution
€ 951 000
Address
Hirosawa 2-1
351 0198 Wako Shi Saitama

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Activity type
Research Organisations
Administrative Contact
Haruo Yamaguchi (Mr.)
INSTITUT PASTEUR
France
EU contribution
€ 800 000
Address
Rue Du Docteur Roux 25-28
75724 Paris Cedex 15

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Activity type
Research Organisations
Administrative Contact
Nadia Khelef (Dr.)
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 760 004
Address
Rue De Tolbiac 101
75654 Paris

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Activity type
Research Organisations
Administrative Contact
Annick Salini (Ms.)
BIOBYTE SOLUTIONS GMBH
Germany
EU contribution
€ 318 600
Address
Bothestrasse 142
69126 Heidelberg

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Ivica Letunic (Dr.)
ACIES Consulting Group SAS
France
EU contribution
€ 295 569,99
Address
Rue De La République 69
69002 Lyon

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Elise Castan (Mrs.)
NOVAMEN SAS

Participation ended

France
EU contribution
€ 167 210,01
Address
Rue De La République 69
69002 Lyon

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Elise Castan (Mrs.)
MATER MEDICAL RESEARCH INSTITUTE LIMITED
Australia
EU contribution
€ 577 570
Address
Level 3 Aubigny Place
South Brisbane

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Activity type
Research Organisations
Administrative Contact
Ian Allan (Mr.)
FONDAZIONE SANTA LUCIA
Italy
EU contribution
€ 574 148
Address
Via Ardeatina 306
00179 Roma

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Activity type
Research Organisations
Administrative Contact
Antonio Lerna (Dr.)
ISTITUTO EUROPEO DI ONCOLOGIA SRL
Italy
EU contribution
€ 1 762 573,32
Address
Via Filodrammatici 10
20121 Milano

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Ilaria Foti (Ms.)
KING'S COLLEGE LONDON
United Kingdom
EU contribution
€ 99 085
Address
Strand
WC2R 2LS London

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Paul Labbett (Mr.)