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Blood regeneration: de novo development of human hematopoietic stem cells

Objective

Hematopoietic stem cells (HSC) are used in clinical therapies for leukemia and blood-related genetic disorders. Whereas
the number of patients requiring treatment continues to increase, HSC transplantations are limited due to insufficient
patient-matched donor HSCs. The current challenge is to create more matched HSCs. As evidenced by the Nobel Prize
award this year, reprogramming of somatic cells to pluripotent stem cells (iPS) is one of the most important breakthroughs
of recent times. This innovative advance contributes to our ability to reprogram patient-specific cells not only to pluripotency, but also to directly program them to other desired cell lineages. The study of healthy and diseased patient cells in this context will have huge impact on the development of new drug and cell-based treatments. My research is uniquely positioned at the interface of fundamental and translational research at the University of Edinburgh Centre for Inflammation Research and Centre for Regenerative Medicine. Through more than a decade of HSC developmental research, my group has shown that HSCs arise from endothelial cells in a natural reprogramming event. We are one of the few groups worldwide that can isolate these special endothelial cells and show that they yield robust transplantable HSCs (the gold-standard for clinically relevant HSCs). Using our unique expertise I aim to foster new translational strategies to de novo generate human HSCs from patient somatic cells. My aims are to 1) mark and manipulate the program for HSC generation during the endothelial to HSC transition (EHT); 2) define extrinsic molecules affecting EHT and engineer novel niches; 3) reprogram human somatic cells or endothelial derived iPS cells directly to HSCs. These aims will be realized through novel multi-color reporter mouse and ES/iPS lines indicating EHT in real-time, allowing for the isolation and functional validation of de novo HSC generation. These novel models and cultures will significantly advance research and technology, to have major impact on the field.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /medical and health sciences/clinical medicine/transplantation
  • /medical and health sciences/clinical medicine/oncology/leukemia

Call for proposal

ERC-2013-ADG
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Host institution

THE UNIVERSITY OF EDINBURGH
Address
Old College, South Bridge
EH8 9YL Edinburgh
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 500 000
Principal investigator
Elaine Anne Dzierzak (Prof.)
Administrative Contact
Alan Kennedy (Mr.)

Beneficiaries (1)

THE UNIVERSITY OF EDINBURGH
United Kingdom
EU contribution
€ 2 500 000
Address
Old College, South Bridge
EH8 9YL Edinburgh
Activity type
Higher or Secondary Education Establishments
Principal investigator
Elaine Anne Dzierzak (Prof.)
Administrative Contact
Alan Kennedy (Mr.)