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Medulloblastoma SIGNED

Molecularly defined models of human childhood brain tumors

Total Cost €

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EC-Contrib. €

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Partnership

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Project "Medulloblastoma" data sheet

The following table provides information about the project.

Coordinator
UPPSALA UNIVERSITET 

Organization address
address: VON KRAEMERS ALLE 4
city: UPPSALA
postcode: 751 05
website: www.uu.se

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 Sweden [SE]
 Project website http://www.igp.uu.se/research/neuro-oncology/fredrik-swartling/
 Total cost 1˙497˙059 €
 EC max contribution 1˙497˙059 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-05-01   to  2020-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UPPSALA UNIVERSITET SE (UPPSALA) coordinator 1˙497˙059.00

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 Project objective

MYC proteins like MYC and MYCN are transcription factors that are mis-regulated in more than half of all types of human cancer including medulloblastoma, the most common brain malignancy in children. The two main challenges that can guide research in the field of pediatric brain tumors is improving survival and reducing long-term detriments due to treatment toxicities, especially from craniospinal radiotherapy. Medulloblastoma is suggested to originate from specific cells in the small brain, cerebellum. These brain tumors have recently been classified into four distinct molecular subgroups and subgroup-specific driver genes have been suggested. However, the precise role of such drivers in tumor initiation and their importance in specifying particular subgroups has not been sufficiently evaluated in proper cells of medulloblastoma origin.

We have generated clinically relevant animal models that carefully resemble some of the defined subgroups of medulloblastoma. In this proposal we intend to use the models to identify the specific cell type these brain tumors originates from. We also aim to refine our medulloblastoma models and develop novel models to define and study cells involved in brain metastasis and tumor recurrence; the main cause of death in brain tumor patients.

We have managed to culture normal human cerebellar stem cells and we now plan to model human medulloblastoma development by overexpressing oncogenes or silencing suppressor genes that are defined as clinically relevant medulloblastoma drivers. We will use a forward genetics screen to identify novel drivers and specifiers of various subtypes of medulloblastoma. We hope these combined efforts will help us better model human medulloblastoma formation and we expect to generate tumors that correlate well, both pathologically and molecularly, with primary cell cultures derived from medulloblastoma patients.

 Publications

year authors and title journal last update
List of publications.
2019 Matko Čančer, Sonja Hutter, Karl O. Holmberg, Gabriela Rosén, Anders Sundström, Jignesh Tailor, Tobias Bergström, Alexandra Garancher, Magnus Essand, Robert J. Wechsler-Reya, Anna Falk, Holger Weishaupt, Fredrik J. Swartling
Humanized Stem Cell Models of Pediatric Medulloblastoma Reveal an Oct4/mTOR Axis that Promotes Malignancy
published pages: , ISSN: 1934-5909, DOI: 10.1016/j.stem.2019.10.005
Cell Stem Cell 25 2019-12-16
2019 Holger Weishaupt, Patrik Johansson, Anders Sundström, Zelmina Lubovac-Pilav, Björn Olsson, Sven Nelander, Fredrik J Swartling
Batch-normalization of cerebellar and medulloblastoma gene expression datasets utilizing empirically defined negative control genes
published pages: 3357-3364, ISSN: 1367-4803, DOI: 10.1093/bioinformatics/btz066
Bioinformatics 35/18 2019-11-26
2016 Aldwin Suryo Rahmanto, Vasil Savov, Andrä Brunner, Sara Bolin, Holger Weishaupt, Alena Malyukova, Gabriela Rosén, Matko Čančer, Sonja Hutter, Anders Sundström, Daisuke Kawauchi, David TW Jones, Charles Spruck, Michael D Taylor, Yoon‐Jae Cho, Stefan M Pfister, Marcel Kool, Andrey Korshunov, Fredrik J Swartling, Olle Sangfelt
FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma
published pages: 2192-2212, ISSN: 0261-4189, DOI: 10.15252/embj.201693889
The EMBO Journal 35/20 2019-05-24

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The information about "MEDULLOBLASTOMA" are provided by the European Opendata Portal: CORDIS opendata.

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