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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.

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

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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