Haematopoietic stem cells (HSCs) support blood system homeostasis 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.
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. 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 established methods to expand transplantable HSCs long-term ex vivo (Wilkinson et al., Nature 2019) and to evaluate the consequences of CRISPR/Cas9 gene editing on functional HSCs in autologous transplant models (Wilkinson et al., Nature Communications 2021). We are now seeking to build on this technology to better understand the biology of HSC self-renewal and lineage commitment, and to develop novel HSC-based therapies.