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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.

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

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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