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Dissection of tumor heterogeneity in vivo

Objective

It is now widely accepted that tumors are composed of heterogeneous population of cells, which contribute
to many aspects of treatment resistance observed in clinic. Despite the acknowledgment of the tumor cell
heterogeneity, little evidence was shown about complexity and dynamics of this heterogeneity in vivo,
mainly because of lacking flexible genetic tools which allow sophisticated analysis in primary tumors. We
recently developed a very efficient mouse somatic brain tumor model which have a full penetrance of high
grade glioma development. Combination of this model with several transgenic mouse lines allow us to
isolate and track different population of cells in primary tumors, most importantly, we also confirmed that
this can be done on single cell level. Here I propose to use this set of valuable genetic tools to dissect the
cellular heterogeneity in mouse gliomas. First we will perform several single cell lineage tracing experiment
to demonstrate the contribution of brain tumor stem cell, tumor progenitors as well as the relatively
differentiated cells, which will provide a complete data sets of clonal dynamics of different tumor cell types.
Second we will further perform this tracing experiment with the presence of conventional chemotherapy.
Third we will perform single cell RNA sequencing experiment to capture the molecular signature, which
determines the cellular heterogeneity, discovered by single cell tracing. This result will be further validated
by analysis of this molecular signatures in human primary tumors. We will also use our established in vivo
target validation approach to manipulate the candidate molecular regulators to establish the functional
correlation between molecular signature and phenotypic heterogeneity. This project will greatly improve our
understanding of tumor heterogeneity, and possibly provide novel approaches and strategies of targeting
human glioblastomas.

Fields of science (EuroSciVoc)

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Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2014-CoG

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Host institution

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 000 000,00
Address
IM NEUENHEIMER FELD 280
69120 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 000 000,00

Beneficiaries (1)

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