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Mead Group: Haematopoietic Stem Cell Biology

MRC Molecular Haematology Unit MRC Weatherall Institute of Molecular Medicine Nuffield Division of Clinical Laboratory Sciences

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 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. The image shows single cell RNA-sequencing analysis of haematopoietic stem/progenitor cells from a patient with a myeloproliferative neoplasm. Each dot represents a single cell. The colour of each dot represents expression of myeloid (blue), erythroid (red) and platelet (green) lineage-associated genes.

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

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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.

Our team

DPHIL SUPERVISOR PROFILE

Haematopoietic Stem Cell Biology

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Selected publications

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.

Related research themes

We seek to understand the causes of diseases of the blood and other malignancies, from a molecular to systems level, with a focus on blood cancers, rare inherited conditions and the tumour microenvironment. We use and develop innovative techniques to drive research in this area, and are committed to bringing about change in clinical diagnosis and practice. Our pathologists discovered many of the biomarkers now used routinely in clinical practice, translate laboratory findings into clinical tests and are developing digital pathology initiatives.
Haematology and Pathology
We are committed to translating our innovative research into clinical benefit. From new methods of diagnosing chronic conditions, to finding the latest treatments for diabetes, cancer, heart disease, stroke and rare diseases, our department is involved in hundreds of clinical studies every year.
Clinical Studies and Trials
Our research is focused on both blood cancers (myeloid and lymphoid malignancies) and solid tumours, such as breast, colorectal, endocrine and lung cancers, with a number of drug discovery efforts and clinical trials taking place within the department. By understanding the basic biology and underlying disease mechanisms we aim to find effective new biomarkers and treatment approaches.
Cancer Biology
Understanding the fundamental biology that drives embryonic development and tissue maintenance provides the basis of much of our research into blood diseases, the cardiovascular system and rare genetic conditions.
Stem Cells and Developmental Biology
Employing a range of genetic techniques, we probe the fundamental causes of disease. Our expertise spans identification of causative genes in rare inherited diseases, through to elucidating complex gene regulatory pathways and exploration of susceptibility to common disease through genome-wide association studies. We use cutting edge techniques to manipulate the genome to determine how particular genes work and study how variants in regulatory DNA may contribute to common disease. An important overall aim is to improve the management of human genetic diseases.
Genetics, Genomics and Genome Biology
We have cutting edge expertise in a range of statistical and mathematical modelling techniques that allow us to interrogate large data sets – from the ‘big data’ of genomics through to magnetic resonance imaging and clinical trials. We are also home to the Medical Research Council WIMM Centre for Computational Biology – a hub for accelerating progress in genomics analysis and single cell biology.
Computational Biology, Statistics and Bioinformatics
A raft of cellular and molecular biology techniques underpin much of the work we do to elucidate the mechanisms of disease. We use established techniques to answer new questions and also develop our own novel and unique methodologies to drive further innovation.
Cellular and Molecular Biology