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The overarching focus of my research group is to characterise genetic and cellular heterogeneity in myeloproliferative neoplasms (MPN) with the ultimate goal to improve the diagnosis, risk-stratification and treatment of these largely incurable forms of blood cancer.


About the Research

We have developed a transformational new technology (TARGET-seq) that enables high-sensitivity detection of multiple mutations in single cells, in parallel with single-cell RNA-seq (scRNA-seq) and cell surface proteomics (Molecular Cell 2019, STAR Protocols, 2020, Patents 1914266.0 and 2007884.6). We applied this and related scRNA-seq approaches to study chronic myeloid leukaemia (Nature Medicine 2017), MPN (Molecular Cell 2019 & 2020) and a rare form of childhood leukaemia, juvenile myelomonocytic leukaemia (Journal of Experimental Medicine, 2021). These studies revealed hitherto unrecognised heterogeneity of cancer stem cells which underlie resistance to therapy and disease progression, leading to the identification of tractable therapeutic targets in MPN. Through additional genetic studies of sporadic and familial MPN, we were the first to describe germline mutations in JAK2 as a cause of hereditary thrombocytosis (NEJM, 2012). We used genetic lineage tracing in monozygotic twins to experimentally demonstrate the prolonged evolutionary dynamics of MPN, which remarkably develop over many decades and may arise in utero despite presenting clinically in adults (Nature Medicine, 2022). I also led genetic analyses of multiple clinical trial cohorts to refine risk-stratification in myeloid malignancies (Blood, 2007, 2008, 2013 & 2019; Leukemia, 2020). Our single-cell genomics work led to the formation of a spin out company with £6M seed investment (Alethiomics). 

We complement our studies of patient samples through the application of cutting-edge mouse models. We described how leukaemia-associated FLT3-ITD mutations subvert lineage commitment and cell-extrinsically suppress normal haematopoietic stem cells by disrupting the bone marrow niche (Cell Reports 2013, J Exp Med 2017). We developed a novel mouse model of early thymic progenitor leukaemia, demonstrating for the first time the cell type that propagates this poor-prognosis leukaemia and also how these leukaemias can be targeted using a novel, epigenetic therapy (Cancer Cell, 2018). We have also demonstrated that the epigenetic regulator Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors (Nature Communications, 2021) and can affect early haematopoiesis through a cell-extrinsic mechanism (Blood 2018).

My scientific programme closely interfaces with my clinical work in Oxford. I am clinical and scientific lead for a number of key MPN clinical trials in the UK and internationally, with extensive associated banking of serial samples by my group at the MRC MHU. We genetically characterise these MPN cohorts to understand how mutation status influences outcome of therapy (Blood 2019, Leukemia 2020) and these studies underpin our single-cell genomics work. 

Students interested in joining the laboratory will have the opportunity to apply the above approaches to study TP53 mutant MPN which has progressed to acute myeloid leukaemia, a blood cancer associated with a very poor prognosis.

Training Opportunities

The Mead laboratory leads on single-cell research at the WIMM and the student will gain a state of the art training in this exciting field. Prof Mead maintains close links with the clinical NHS haematology department in Oxford, key to obtain patient samples and enable the translation of scientific research into clinical practice. Previous students in the Mead Laboratory have conducted highly successful DPhils. For example, Christopher Booth (completed Jan 2018) was awarded the Ita Askonas Medal for best DPhil student presentation at the WIMM day in 2016, the RDM Graduate Prize in 2018 and published a first author paper in Cancer Cell. Alba Rodriguez-Meira (year 4 DPhil student in the Mead Lab) developed TARGET-seq, was awarded the Ita Askonas Medal for best DPhil student presentation in 2018 and has a paper in Molecular Cell in year 3 of her studies. I have supervised students through wet-lab and computationally focused PhDs, or a combination of the two!

Students will be enrolled on the MRC WIMM 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 MRC 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 MRC 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.




Louka E*, Povinelli B*, Rodriguez-Meira A, Buck G, Wen WX, Wang G, Sousos N, Ashley N, Hamblin A, Booth CAG, Roy A, Elliott N, Iskander D, de la Fuente J, Fordham N, O'Byrne S, Inglott S, Norfo R, Salio M, Thongjuea S, Rao A, Roberts I+,Mead AJ+. Heterogeneous disease-propagating stem cells in juvenile myelomonocytic leukemia. J Exp Med. 2021;218(2).  +,* Equal contribution. Cover image and featured article with commentary ‘Stem cell origins of JMML’.


Psaila B*, Wang G*, Rodriguez-Meira A, Li R, Heuston EF, Murphy L, Yee D, Hitchcock IS, Sousos N, O'Sullivan J, Anderson S, Senis YA, Weinberg OK, Calicchio ML, Center NIHIS, Iskander D, Royston D, Milojkovic D, Roberts I, Bodine DM, Thongjuea SMead AJ. Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets. Mol Cell. 2020;78(3):477-92 e8. *Equal contribution.


Rodriguez-Meira A, Buck G, Clark SA, Povinelli BJ, Alcolea V, Louka E, McGowan S, Hamblin A, Sousos N, Barkas N, Giustacchini A, Psaila B, Jacobsen SEW, Thongjuea S, Mead AJ. Unravelling Intratumoral Heterogeneity through High-Sensitivity Single-Cell Mutational Analysis and Parallel RNA Sequencing. Mol Cell. 2019;73(6):1292-305 e8. Cover image and featured article.


Booth CAG, Barkas N+, Neo WH+, Boukarabila H, Soilleux EJ, Giotopoulos G, Farnoud N, Giustacchini A, Ashley N, Carrelha J, Jamieson L, Atkinson D, Bouriez-Jones T, Prinjha RK, Milne TA, Teachey DT, Papaemmanuil E, Huntly BJP, Jacobsen SEW*Mead AJ*à. Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors. Cancer Cell. 2018;33(2):274-91 e8.+,* Equal contribution. àLead corresponding author


Mead AJ, Neo WH, Barkas N, Matsuoka S, Giustacchini A, Facchini R, Thongjuea S, Jamieson L, Booth CAG, Fordham N, Di Genua C, Atkinson D, Chowdhury O, Repapi E, Gray N, Kharazi S, Clark SA, Bouriez T, Woll P, Suda T, Nerlov C, Jacobsen SEW. Niche-mediated depletion of the normal hematopoietic stem cell reservoir by Flt3-ITD-induced myeloproliferation. J Exp Med. 2017;214(7):2005-21. Featured article.


Giustacchini A+, Thongjuea S+, Barkas N, Woll PS, Povinelli BJ, Booth CAG, Sopp P, Norfo R, Rodriguez-Meira A, Ashley N, Jamieson L, Vyas P, Anderson K, Segerstolpe A, Qian H, Olsson-Stromberg U, Mustjoki S, Sandberg R, Jacobsen SEW*, Mead AJ*. Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. Nat Med. 2017;23(6):692-702. +,* Equal contribution. Cover image and featured article.


Psaila B, Barkas N+, Iskander D+, Roy A, Anderson S, Ashley N, Caputo VS, Lichtenberg J, Loaiza S, Bodine DM, Karadimitris A, Mead AJ*, Roberts I*. Single-cell profiling of human megakaryocyte-erythroid progenitors identifies distinct megakaryocyte and erythroid differentiation pathways. Genome Biol. 2016;17:83.. +,* Equal contribution.