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. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsgenomesnatural scienceschemical scienceselectrochemistrybioelectrochemistryelectroporation Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-StG-2014 - ERC Starting Grant Call for proposal ERC-2014-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution UPPSALA UNIVERSITET Net EU contribution € 1 497 059,00 Address VON KRAEMERS ALLE 4 751 05 Uppsala Sweden See on map Region Östra Sverige Östra Mellansverige Uppsala län Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 497 059,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UPPSALA UNIVERSITET Sweden Net EU contribution € 1 497 059,00 Address VON KRAEMERS ALLE 4 751 05 Uppsala See on map Region Östra Sverige Östra Mellansverige Uppsala län Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 497 059,00