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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.

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

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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