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Marcus Järså

CRISPR/Cas9 Screens to Identify New Therapeutic Targets in Leukemia

This project aims to identify new therapeutic targets on the cell surface of leukemia stem cells. By developing antibodies directed towards these candidate therapeutic targets and test them in preclinical models, the project will provide proof of concept for therapeutic efficacy in leukemia.

Background

Acute myeloid leukemia (AML) is a fatal disorder with a five-years survival of around 25%. The reason AML often relapses after initial remissions following treatments has been attributed to the AML stem cells, which show resistance to conventional cancer therapies. Thus, new therapeutic approaches targeting AML stem cells are needed.

Aim of the project

The overall aim of this project is to use state-of-the-art screening strategies to identify novel therapeutic targets on AML stem cells, and to provide proof of concept for therapeutic effect by targeting leukemia stem cells using antibodies in preclinical models.

Project description

By using the CRISPR/Cas9-technology and transgenic mouse models, the PhD student will search for cell surface proteins critical for the growth and survival of leukemia stem cells. The expression pattern of the identified cell surface proteins in AML stem cell-enriched cell populations will be investigated using multi-parameter flow cytometry. Finally, the biological roles and therapeutic potential of targeting the identified cell surface molecules will be investigated using leukemia mouse models.

Significance

The proposed studies represent novel and innovative approaches to identify new therapeutic cell surface targets in AML and expand our knowledge regarding cell surface molecules regulating AML stem cells. Moreover, the project will provide proof of concept for therapeutic effect by targeting AML stem cells, findings that may translate into new therapeutic opportunities in AML, a disease associated with dismal prognosis.

Lund University Research Portal

Page Manager:

Marcus Järås

Associate Professor

 

E-mail:

marcus.jaras@med.lu.se

Phone:

+46 72 387 36 03

 

Department of Laboratory Medicine

Division of Clinical Genetics

 

BMC C1315b

Sölvegatan 19

221 84 Lund