PhD MRCP FRCPath
Professor of Haematology
- Consultant Physician
- MRC Senior Clinical Fellow
Leukaemia Stem Cell Biology
I trained in medicine and haematology at the University of Oxford and UCL and completed my PhD at UCL in 2007 with Professors Rosemary Gale and David Linch. My PhD was focused on the clinical impact of different types of FLT3 mutation in acute myeloid leukaemia. I then was awarded a LRF (now Bloodwise) Senior Bennett Fellowship to work on the haematopoietic impact of FLT3 mutations with Professor Sten Eirik Jacobsen in Oxford prior to setting up my own research group funded by a MRC Senior Clinical Fellowship in 2014.
My research is focused on understanding how the normal haematopoietic stem/progenitor hierarchy is disrupted during the development of myeloid malignancies. The overarching aim of my research group is to improve the management of myeloproliferative neoplasms (MPN), chronic myeloid leukaemia (CML) and related conditions through better characterisation and therapeutic targeting of malignant stem and progenitor cell populations. My research is closely linked with my clinical practice based at Oxford University Hospitals NHS Trust where I am clinical lead for MPN and CML.
My laboratory has a particular interest in the development and application of single cell genomics techniques to analyse malignant stem cell populations. We have used this approach to analyse leukaemia stem cells in patients with CML, MPN, juvenile myelomonocytic leukaemia (JMML) and related conditions. We are also applying this approach to analyse patients receiving novel targeted therapies in order to better understand mechanisms of resistance to molecularly targeted therapy in stem cell populations and pathways of transformation to more aggressive forms of disease.
We use a variety of other experimental approaches to analyse stem cells in MPNs including:
- Development of genetically engineered models of myeloid malignancies which provide an ideal platform for in vivo pre-clinical development of novel therapies.
- Characterisation of cell-extrinsic regulators of haematopoietic stem/progenitor cells, including bone marrow niche populations, and how these are disrupted in in myeloid malignancies.
- Identification of somatic and germline genetic abnormalities in myeloid malignancies. Our particular focus is to refine risk stratification of patients using these molecular markers.
I lead the NIHR MPN Clinical Studies Subgroup which oversees MPN clinical research in the UK and I am the Principal or Chief Investigator of over 28 clinical trials in MPNs, including access to extensive sample collections linked to these clinical trials.
Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.
Giustacchini A. et al, (2017), Nat Med, 23, 692 - 702
Myeloproliferative neoplasm stem cells.
Mead AJ. and Mullally A., (2017), Blood, 129, 1607 - 1616
Single-cell profiling of human megakaryocyte-erythroid progenitors identifies distinct megakaryocyte and erythroid differentiation pathways.
Psaila B. et al, (2016), Genome Biol, 17
Application of single-cell genomics in cancer: promise and challenges.
Wills QF. and Mead AJ., (2015), Hum Mol Genet, 24, R74 - R84
Germline JAK2 mutation in a family with hereditary thrombocytosis.
Mead AJ. et al, (2012), N Engl J Med, 366, 967 - 969
VALERIE: Visual-based inspection of alternative splicing events at single-cell resolution.
Wen WX. et al, (2020), PLoS Comput Biol, 16
Spliceosome mutations are common in persons with myeloproliferative neoplasm-associated myelofibrosis with RBC-transfusion-dependence and correlate with response to pomalidomide
Chowdhury O., (2020), Leukemia
A British Society for Haematology Guideline on the diagnosis and management of chronic myeloid leukaemia.
Smith G. et al, (2020), Br J Haematol
Artificial intelligence-based morphological fingerprinting of megakaryocytes: a new tool for assessing disease in MPN patients.
Sirinukunwattana K. et al, (2020), Blood Adv, 4, 3284 - 3294
Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort.
Thaventhiran JED. et al, (2020), Nature