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iGBMavatars SIGNED

Glioblastoma Subtype Avatar models for Target Discovery and Biology

Total Cost €

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EC-Contrib. €

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Partnership

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 iGBMavatars project word cloud

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

rats    mutually    proneural    basis    combine    give    tumor    tumors    intervention    immunocompromised    immunophenotypic    glioblastoma    lethal    gbm    stem    dna    transcriptome    conceivably    engineered    standard    copy    benefit    nsc    gliomas    subtypes    fit    profiles    multiforme    mutations    human    adult    supports    gene    therapies    mesenchymal    profiling    favoring    genetic    primary    methylation    therapy    generate    lesions    ing    cells    avatars    humanized    experimental    subtype    expression    oncology    models    dismal    vivo    histopathology    personalized    neural    translation    recurrently    implanted    urging    patients    questions    treatments    agents    grade    screening    resistance    aberrations    synthetic    point    clinical    orthotopically    first    care    biology    drug    appropriate    crispri    convey    treatment    reflecting    chosen    exists    heterogeneity    rapid    accurately    epigenomic    interactions    entry    profiled    incurable    molecular    gsa    disease    fingerprinting    vulnerabilities    tracing    create    xenografts    biopsies    exclusive    seek    damaging    brain    patient    screens    exploited   

Project "iGBMavatars" data sheet

The following table provides information about the project.

Coordinator
MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) 

Organization address
address: ROBERT ROSSLE STRASSE 10
city: BERLIN
postcode: 13125
website: www.mdc-berlin.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˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-07-01   to  2022-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) DE (BERLIN) coordinator 1˙500˙000.00

Map

 Project objective

The Glioblastoma Multiforme (GBM) is the most common primary brain tumor and it is incurable. Two major challenges affect GBM clinical management: its heterogeneity (which treatment will best fit this very patient?) and its resistance to available treatments (will the patient benefit in any way from the chosen therapy?). Here we approach these questions with a personalized entry point. First, we aim to create “humanized” experimental models of GBM accurately reflecting patients at molecular level. These GBM Subtype Avatars models (GSA) will be exploited as “targeted patients” in personalized biology and intervention studies. Since GBM exists as molecular subtypes with similar histopathology but mutually exclusive genetic lesions and molecular features, we will generate GSA by targeting mutations recurrently associated with Proneural, Classical or Mesenchymal GBM subtypes into adult human neural stem cells (NSC). Evidence supports that these cells can give rise to high-grade gliomas when engineered with the appropriate genetic lesions. Next, engineered NSC will be orthotopically implanted into immunocompromised rats and the resulting tumors profiled for gene expression, DNA methylation and copy number aberrations. These profiles will be compared to those generated in patient-derived xenografts and biopsies. Second, to identify drug targets favoring patients’ response to the current standard of care, we will exploit GSA for state-of-art genetic screens in vivo. Specifically, we will seek for synthetic lethal interactions between DNA damaging agents and the GSA transcriptome using an in vivo CRISPRi screening approach. Third, to investigate the molecular basis of GBM heterogeneity in GSA models, we will combine genetic and immunophenotypic tracing with gene expression and epigenomic profiling. Identifying tumor-specific vulnerabilities in a dismal disease urging for effective therapies and its molecular fingerprinting convey conceivably rapid Translation in Oncology.

 Publications

year authors and title journal last update
List of publications.
2018 Gaetano Gargiulo
Next-Generation in vivo Modeling of Human Cancers
published pages: , ISSN: 2234-943X, DOI: 10.3389/fonc.2018.00429
Frontiers in Oncology 8 2019-05-14

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