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In Vitro and in Vivo Screens for Novel Regulators in Leukemia (NOREL)

Project information

Grant agreement ID: 273701

Status

Closed project

  • Start date

    1 April 2012

  • End date

    31 March 2014

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 219 590,40

  • EU contribution

    € 219 590,40

Coordinated by:

KOBENHAVNS UNIVERSITET

Denmark

Objective

"Leukemic cells, similar to other types of cancer cells, are characterized by aberrant epigenetic changes, which often lead to abnormal expression of oncogenes and tumor suppressor genes. The goal of this project is to identify and characterize new regulators of normal and malignant hematopoiesis. We propose two complementary loss-of-function screens, using shRNA vectors against two groups of histone modifying enzymes, histone methyltransferases and histone demethylases.

We plan to perform an in vitro shRNA screen, infecting mouse primary cells with lentiviruses based on single pLKO.1 vectors. We will assess the effect of down-regulation of a specific protein by flow cytometry analysis. In parallel, we will carry out an in vivo shRNA screen in a mouse model of human acute myeloid leukemia (AML). Mouse leukemic cells will be infected with a pooled retroviral shRNA library and transplanted into a small number of recipient mice. When the recipient mice develop AML, the leukemic cells will be harvested and high-throughput sequencing of shRNAs will be used to determine shRNAs depleted or enriched during initiation and progression of AML.

Selected candidate genes will be validated and further characterized using in vitro and in vivo assays. Moreover, we will search for molecular mechanisms mediating the function of validated candidates in normal hematopoiesis and/or leukemia. I strongly believe that this project can lead to a discovery of novel oncogenes and/or tumor suppressors involved in AML, and potentially also to design of novel therapies for leukemia treatment."

Coordinator

KOBENHAVNS UNIVERSITET

Address

Norregade 10
1165 Kobenhavn

Denmark

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 219 590,40

Administrative Contact

Ivan Kristoffersen (Mr.)

Project information

Grant agreement ID: 273701

Status

Closed project

  • Start date

    1 April 2012

  • End date

    31 March 2014

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 219 590,40

  • EU contribution

    € 219 590,40

Coordinated by:

KOBENHAVNS UNIVERSITET

Denmark