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Haematopoietic stem cells (HSCs) support blood system homeostasis and are also used clinically in cell and gene therapies. We are interested in studying the biology of this important stem cell population and developing new HSC-based therapies.

Ex vivo haematopoietic stem cell expansion graphic

ABOUT THE 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. We are aiming to improve the safety, availability, and potential applications of HSC-based therapies through developing new tools to expand and modify HSCs 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., bioRxiv 2020). We are now seeking to build on this technology to develop novel HSC-based therapies. These methods also provide new opportunities to better understand the biology of HSC self-renewal and lineage commitment. We are looking for an enthusiastic student to build our team working on:

  1. Characterizing ex vivo self-renewing HSCs at the molecular and genetic levels
  2. Developing novel HSC gene editing and transplantation technologies
  3. Establishing and characterising long-term ex vivo human HSC expansion cultures

Informal enquiries are welcome and can be directed to Adam Wilkinson (adamcw@stanford.edu).

TRAINING OPPORTUNITIES

Training in haematopoietic stem cell biology and experimental haematology available. This may include ex vivo HSC expansion methodologies, functional HSC transplantation assays, CRISPR/Cas9 genome engineering, genetic screening, genomic approaches, single cell assays, flow cytometry and fluorescence activated cell sorting (FACS), molecular cloning, and mouse modelling. Opportunities to work with collaborators in Oxford and elsewhere (UK, Japan, USA) available.

Students will be enrolled on the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

All WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework. The RDM also holds an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

 

PUBLICATIONS

Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M, Crisostomo RV, Yamamoto R, Loh KM, Nakamura Y, Watanabe M, Nakauchi H, Yamazaki S. Long-term ex vivo hematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature 2019. 571(7763):117-121.

Wilkinson AC, Dever DP, Baik R, Camarena J, Hsu I, Charlesworth CT, Morita C, Nakauchi H, Porteus MH. Cas9-AAV6 Gene Correction of Beta-Globin in Autologous HSCs Improves Sickle Cell Disease Erythropoiesis in Mice. bioRxiv. 2020; DOI:10.1101/2020.10.13.338319

Wilkinson AC, Ishida R, Nakauchi H, Yamazaki S. Long-term ex vivo expansion of mouse hematopoietic stem cells. Nature Protocols 2020. 15(2):628-648.

Nishimura T, Hsu I, Martinez-Krams DC, Nakauchi Y, Majeti R Yamazaki S, Nakauchi H, Wilkinson AC. Use of polyvinyl alcohol for CAR T cell expansion. Experimental Hematology 2019. 80:16-20.

Wilkinson AC, Igarashi KJ, Nakauchi H. Haematopoietic stem cell self-renewal in vivo and ex vivo. Nature Reviews Genetics. 2020; 21(9):541-554.

Wilkinson AC, Ballabio E, Geng H, North P, Tapia M, Kerry J, Biswas D, Roeder RG, Allis CD, Melnick A, de Bruijn MF, Milne TA. RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction. Cell Reports. 2013; 3(1):116-27.