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UNEXPECTED SIGNED

Uncovering targets for ex vivo expansion of hematopoietic stem cells to enhance cell therapies of blood disorders

Total Cost €

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EC-Contrib. €

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Partnership

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Project "UNEXPECTED" data sheet

The following table provides information about the project.

Coordinator
LUNDS UNIVERSITET 

Organization address
address: Paradisgatan 5c
city: LUND
postcode: 22100
website: n.a.

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.lu.se
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-08-01   to  2020-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    LUNDS UNIVERSITET SE (LUND) coordinator 2˙000˙000.00

Map

 Project objective

Mechanisms of self-renewal in hematopoietic stem cells (HSCs) have been subject to intense studies during the last decades. However, this is still a poorly defined process and very limited progress has been made in the long sought goal of expanding HSCs ex vivo to allow for critical improvements of bone marrow transplantation procedures for cancer patients and potentially a broader use of HSCs in gene therapy and regenerative medicine. The aim of this research program is to systematically identify and characterize regulators of self-renewal in human HSCs and to develop strategies for stem cell expansion. Within the project we will develop novel paradigms for CRISPR (clustered regularly interspaced short palindromic repeats) mediated gene editing in primary human HSCs to enable detailed assessment of gene function. We will further employ forward genetic screening approaches based on both CRISPR/Cas9 gene editing and RNA interference (RNAi) gene silencing to identify regulators of renewal and differentiation in human HSCs. Large numbers of HSCs will be targeted with genome-wide lentiviral CRISPR (sgRNA) and short hairpin RNA (shRNA) libraries. Screening assays for HSC self-renewal will be evaluated in a pooled format and de-convoluted using next generation sequencing, allowing thousands of perturbations to be assayed in parallel. Candidate genes from the screens will be studied further using genetic barcoding and transplantations assays in immundeficient mice to test whether they can be targeted to induce expansion of HSCs ex vivo. Finally, based on our findings, we aim to develop GMP compatible conditions for HSC expansion in preparation for clinical trials involving expansion of umbilical cord blood derived stem cells to treat patients with acute leukemia.

 Publications

year authors and title journal last update
List of publications.
2018 Mehrnaz Safaee Talkhoncheh, Agatheeswaran Subramaniam, Mattias Magnusson, Praveen Kumar, Jonas Larsson, Aurélie Baudet
Transient inhibition of NF-κB signaling enhances ex vivo propagation of human hematopoietic stem cells
published pages: 1444-1450, ISSN: 0390-6078, DOI: 10.3324/haematol.2018.188466
Haematologica 103/9 2019-04-18
2017 Justyna Rak, Katie Foster, Katarzyna Potrzebowska, Mehrnaz Safaee Talkhoncheh, Natsumi Miharada, Karolina Komorowska, Therese Torngren, Anders Kvist, Ã…ke Borg, Lena Svensson, Dominique Bonnet, Jonas Larsson
Cytohesin 1 regulates homing and engraftment of human hematopoietic stem and progenitor cells
published pages: 950-958, ISSN: 0006-4971, DOI: 10.1182/blood-2016-06-720649
Blood 129/8 2019-06-07
2016 Roman Galeev, Aurélie Baudet, Praveen Kumar, Alexandra Rundberg Nilsson, Björn Nilsson, Shamit Soneji, Therese Törngren, Åke Borg, Anders Kvist, Jonas Larsson
Genome-wide RNAi Screen Identifies Cohesin Genes as Modifiers of Renewal and Differentiation in Human HSCs
published pages: 2988-3000, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.02.082
Cell Reports 14/12 2019-06-07

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