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Wilkinson Group: Blood Stem Cell Expansion and Fitness

MRC Molecular Haematology Unit MRC Weatherall Institute of Molecular Medicine

Haematopoietic stem cells (HSCs) support blood cell production throughout life and are also used clinically in cell and gene therapies. We are studying the biology of this important stem cell population with the aim of developing new HSC-based therapies.

Research:

Multipotent and self-renewing HSCs sustain our haematopoietic systems throughout life. In the clinic, HSC transplantation therapy currently represents the only curative treatment option for numerous haematological malignancies. Additionally, HSC-based gene therapies are being developed and used to correct various hereditary blood diseases. However, while potentially curative, these HSC transplantation therapies still represent a high-risk procedure and are not available to all patients. We are aiming to improve the safety, availability, and potential applications of HSC-based therapies through developing new tools to expand and modify HSC fitness and activity ex vivo.

Towards this goal, we recently pioneered new methods to expand transplantable HSCs long-term ex vivo (Wilkinson et al., Nature 2019; Igarashi et al., Blood Advances 2023; Sakurai et al., Nature 2023) and to evaluate the consequences of CRISPR/Cas9 gene editing on functional HSCs in autologous transplant models (Wilkinson et al., Nature Communications 2021; Becker et al., Cell Stem Cell 2023). We are now seeking to build on this technology to better understand the biology of HSC self-renewal and lineage commitment (Haney et a., bioRxiv 2022), and to develop novel HSC-based therapies.

 

Lab funding generously provided by:

Kay Kendall Leukaemia Fund

European Hematology Association

National Institute of Health and Care Research

John Fell Fund

MRC

 

Lab Resources:

https://www.hematopoiesiscrisprscreens.com/

https://bgwebserver2.stemcells.cam.ac.uk/Igarashi2022/

 

Lab alumni:

Hwei Minn Khoo (research assistant) - currently a PhD student at ICR London

Ethan Sip (summer undergraduate) - currently completing MBiochem at Oxford

Our team

DPhil Projects Available

Wilkinson Group - From basic biology to novel translational applications of haematopoietic stem cells

Selected publications

More publications

Related research themes

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Stem Cells and Developmental Biology
A raft of cellular and molecular biology techniques underpin much of the work we do to elucidate the mechanisms of disease. We use established techniques to answer new questions and also develop our own novel and unique methodologies to drive further innovation.
Cellular and Molecular Biology
We use state of the art techniques to interrogate the intricacies of our body’s response to pathogens, cancer and non-communicable diseases. We have particular strengths in T cell signaling, the innate immune system and therapeutic antibody development – particularly in oncology and against pathogens. We have forged strong links with clinical medicine to accelerate translation of laboratory studies into therapeutic strategies.
Immunology and Infection
Employing a range of genetic techniques, we probe the fundamental causes of disease. Our expertise spans identification of causative genes in rare inherited diseases, through to elucidating complex gene regulatory pathways and exploration of susceptibility to common disease through genome-wide association studies. We use cutting edge techniques to manipulate the genome to determine how particular genes work and study how variants in regulatory DNA may contribute to common disease. An important overall aim is to improve the management of human genetic diseases.
Genetics, Genomics and Genome Biology
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Haematology and Pathology