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.
A Randomized, Phase 3, Trial of Interferon-α versus Hydroxyurea in Polycythemia Vera and Essential Thrombocythemia.
Mascarenhas J. et al, (2022), Blood
Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors.
Neo WH. et al, (2021), Nat Commun, 12
A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program.
Rice S. et al, (2021), Nat Commun, 12
CPI-0610, A BROMODOMAIN AND EXTRATERMINAL DOMAIN (BET) PROTEIN INHIBITOR, IN COMBINATION WITH RUXOLITINIB, IN JAK INHIBITOR-NAIVE MYELOFIBROSIS PATIENTS: UPDATE OF MANIFEST PHASE 2 STUDY
Palandri F. et al, (2021), HAEMATOLOGICA, 106, 5 - 6
THE BET INHIBITOR, CPI-0610, PROMOTES MYELOID DIFFERENTIATION IN MYELOFIBROSIS (MF) PATIENT BONE MARROW AND PERIPHERAL CD34+HEMATOPOIETIC STEM CELLS
Vannucchi A. et al, (2021), HAEMATOLOGICA, 106, 51 - 51