Mead Group: Haematopoietic Stem Cell Biology
The Haematopoietic Stem Cell Biology (HSCB) Laboratory is focused on understanding how the normal haematopoietic stem/progenitor hierarchy is disrupted during the development of myeloid malignancies. Our overarching aim is to improve the management of myeloproliferative neoplasms and related conditions through better monitoring and therapeutic targeting of malignant stem cell populations.
The major focus of our research programme is to identify and genetically model leukaemic and pre-leukaemic stem cells in myeloid malignancies. Our overarching aim is to better characterise the cellular and molecular biology of these key populations of cells in order to understand how malignant stem cell populations might be more effectively targeted and eradicated. In order to achieve this, we are applying a number of approaches:
1. Development of genetically engineered models of myeloid malignancies in order to study the impact of specific driver mutation(s) on the establishment, evolution and propagation of leukaemic stem cells. These models provide an ideal platform for in vivo pre-clinical development of novel therapies.
2. Analysis of leukaemia stem cells in patients with chronic myeloid leukaemia, myeloproliferative neoplasms, juvenile myelomonocytic leukaemia and related
conditions. We have developed new methods to study the molecular signatures of normal and malignant stem cell populations at the single-cell level. This is crucial in order to unravel the intratumoural heterogeneity within any phenotypically defined malignant stem cell population. 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.
3. Identification of somatic and germline genetic abnormalities associated with the development of myeloid malignancies. Our particular focus is to refine risk stratification of patients using these molecular markers and also to gain a better understanding of how germline mutations might disrupt stem/progenitor cell populations to promote the development of myeloid malignancies.
4. Characterisation of cell-extrinsic regulators of haematopoietic stem/progenitor cells, including bone marrow niche populations, and how they are disrupted during the development of myeloproliferative neoplasms and related conditions.
Clinical Studies and Trials
Professor Mead’s clinical research is based at the Churchill Hospital in Oxford. He leads the clinical service for patients with myeloproliferative neoplasms (MPN) and chronic myeloid leukaemia (CML) in the Thames Valley and is chair of the National Cancer Research Institute MPN Clinical Studies Subgroup which oversees clinical research in the UK focused on these diseases. Professor Mead is the Principal or Chief Investigator of over 28 clinical trials in CML and MPNs.
Learn more about MPN clinical research in the UK.