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Normal and Leukaemic Haemopoiesis: Understanding the fundamental biological processes underlying normal and malignant haematopoiesis and translate this to improve patient outcomes through new rational therapies.


Project Description

Understanding the fundamental biological processes underlying normal and malignant haematopoiesis and translate this to improve patient outcomes through new rational therapies.

The main focus of the laboratory is understand human haemopoiesis, both normal and leukaemic. Our work also uses mouse models when appropriate. We focus on purifying normal and leukaemic human stem and progenitor populations[1-3] as this is a required base to the molecular mechanisms of how different leukaemogenic mutations cause differentiation arrest. We also study the mechanistic basis of clonal response and resistance to novel anti-leukaemic therapy[4]. Our expertise is complex flow cytometry, single cell analysis of RNA, chromatin and mutational profile in normal and leukaemic cells. We have particular expertise in study of primary human cells. Finally, we are developing novel models to study niche function and the immune response to leukaemia.

The type of projects a candidate may work on include: (i) defining the heterogeneity of normal human stem cells by purifying the most potent stem cells and understanding if they have lineage bias (a collaborative project with Professor Claus Nerlov). We also study mechanisms involved in the differentiation of early normal haemopoietic progenitors and in this regard we are undertaking in vivo bar-coding and single cell systems approaches. We collaborate with the Nerlov and Gottgens laboratories on these projects. We have projects on transcriptional deregulation in acute myeloid leukaemia (some in collaboration with Professor Irene Roberts), clonal haemopoiesis and understanding the role of the niche in clonal haemopoiesis and in acute myeloid leukaemia. Much of the work is focussed on specific mechanistic questions.

The projects and laboratory will provide high quality training in stem/progenitor purification and cell biology, single cell analysis of RNA, chromatin and DNA, cancer biology (using leukaemia as a model) and immune responses in cancer. Successful applicants will develop transferable skills in bench science and computational biology (including coding), as well critical ability to evaluate scientific data and place that data in the context of a field. Presentational and writing skills are also highly valued. We have weekly laboratory meetings and a separate journal club.

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

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold 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.

Funding Notes

Our main deadline for applications for funded places has now passed. Supervisors may still be able to consider applications from students who have alternative means of funding (for example, charitable funding, clinical fellows or applicants with funding from a foreign government or equivalent). Prospective applicants are strongly advised to contact their prospective supervisor in advance of making an application.

Please note that any applications received after the main funding deadline will not be assessed until all applications that were received by the deadline have been processed. This may affect supervisor availability.

References

Goardon, N., E. Marchi, A. Atzberger, L. Quek, A. Schuh, S. Soneji, P. Woll, A. Mead, K.A. Alford, R. Rout, S. Chaudhury, A. Gilkes, S. Knapper, K. Beldjord, S. Begum, S. Rose, N. Geddes, M. Griffiths, G. Standen, A. Sternberg, J. Cavenagh, H. Hunter, D. Bowen, S. Killick, L. Robinson, A. Price, E. Macintyre, P. Virgo, A. Burnett, C. Craddock, T. Enver, S.E. Jacobsen, C. Porcher, and P. Vyas, Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell, 2011. 19(1): p. 138-52.

Quek, L., G.W. Otto, C. Garnett, L. Lhermitte, D. Karamitros, B. Stoilova, I.J. Lau, J. Doondeea, B. Usukhbayar, A. Kennedy, M. Metzner, N. Goardon, A. Ivey, C. Allen, R. Gale, B. Davies, A. Sternberg, S. Killick, H. Hunter, P. Cahalin, A. Price, A. Carr, M. Griffiths, P. Virgo, S. Mackinnon, D. Grimwade, S. Freeman, N. Russell, C. Craddock, A. Mead, A. Peniket, C. Porcher, and P. Vyas, Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage. J Exp Med, 2016. 213(8): p. 1513-35.

Karamitros, D., B. Stoilova, Z. Aboukhalil, F. Hamey, A. Reinisch, M. Samitsch, L. Quek, O. G., E. Repapi, J. Doondeea, B. Usukhbayar, J. Calvo, S. Taylor, N. Goardon, E. Six, F. Pflumio, C. Porcher, R. Majeti, B. Gottgens, and P. Vyas, Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells. Nature Immunology, 2018. 19: p. 85-97.

Quek, L., M.D. David, A. Kennedy, M. Metzner, M. Amatangelo, A. Shih, B. Stoilova, C. Quivoron, M. Heiblig, C. Willekens, V. Saada, S. Alsafadi, M.S. Vijayabaskar, A. Peniket, O.A. Bernard, S. Agresta, K. Yen, K. MacBeth, E. Stein, G.S. Vassiliou, R. Levine, S. De Botton, A. Thakurta, V. Penard-Lacronique, and P. Vyas, Clonal heterogeneity of acute myeloid leukemia treated with the IDH2 inhibitor enasidenib. Nat Med, 2018. 24(8): p. 1167-1177.

How good is research at University of Oxford in Clinical Medicine?

FTE Category A staff submitted: 238.51

Research output data provided by the Research Excellence Framework (REF)

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