A5053302921- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Platelet Disorders and Treatments
- Blood groups and transfusion
- Single-cell and spatial transcriptomics
- Chronic Myeloid Leukemia Treatments
- Eosinophilic Disorders and Syndromes
- Blood properties and coagulation
- Kruppel-like factors research
- Hematological disorders and diagnostics
- Hematopoietic Stem Cell Transplantation
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Erythrocyte Function and Pathophysiology
- Immune cells in cancer
- Chronic Lymphocytic Leukemia Research
- Autoimmune Bullous Skin Diseases
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Hemoglobinopathies and Related Disorders
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Acute Lymphoblastic Leukemia research
- Bone and Joint Diseases
MRC Weatherall Institute of Molecular Medicine
2017-2025
University of Oxford
2017-2025
Oxford University Hospitals NHS Trust
2020-2025
National Heart Lung and Blood Institute
2025
Ludwig Cancer Research
2024-2025
Medical Research Council
2018-2024
National Institute for Health Research
2019-2024
Churchill Hospital
2020-2023
St Thomas' Hospital
2022-2023
Oxford BioMedica (United Kingdom)
2018-2023
The pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP) involves antibody-mediated platelet destruction and reduced production. Stimulation production may be an effective treatment for this disorder.We conducted a trial in which 118 adults with ITP counts less than 30,000 per cubic millimeter who had relapses or whose count was refractory to at least one standard were randomly assigned receive the oral thrombopoietin-receptor agonist eltrombopag (30, 50, 75 mg daily) placebo....
Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for resolving transcriptional heterogeneity. However, its application to studying cancerous tissues is currently hampered by the lack of coverage across key mutation hotspots in vast majority cells; this prevents correlation genetic and readouts from same single cell. To overcome this, we developed TARGET-seq, method high-sensitivity detection multiple mutations within cells both genomic coding DNA, parallel with unbiased...
Abstract A lack of models that recapitulate the complexity human bone marrow has hampered mechanistic studies normal and malignant hematopoiesis validation novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, hematopoietic lineages. These 3D structures capture key features marrow—stroma, lumen-forming sinusoids, myeloid including proplatelet-forming...
Abstract Understanding the genetic and nongenetic determinants of tumor protein 53 ( TP53 ) - mutation-driven clonal evolution subsequent transformation is a crucial step toward design rational therapeutic strategies. Here we carry out allelic resolution single-cell multi-omic analysis hematopoietic stem/progenitor cells (HSPCs) from patients with myeloproliferative neoplasm who transform to TP53- mutant secondary acute myeloid leukemia (sAML). All showed dominant ‘multihit’ HSPC clones at...
<b>Background:</b> Over the past five years, in most hospitals England and Wales, incident reporting has become well established but it remains unclear how reports match clinical adverse events. International epidemiological studies of events are based on retrospective, multi-hospital case record review. In this paper authors describe use reporting, pharmacist surveillance local real-time review for recognition risks associated with hospital inpatient care. <b>Methodology:</b> Data were...
Summary A method for objective quantification of bleeding symptoms in immune thrombocytopenic purpura (ITP) has not been established. The ITP Bleeding Scale (IBLS) is a novel assessment system comprising 11 site‐specific grades. Implementation the IBLS on 100 patient visits revealed that although platelet count and large correlated well with overall, this relationship disappeared marked thrombocytopenia. useful clinical tool monitoring may be used to aid development laboratory parameters...
Recent advances in single-cell techniques have provided the opportunity to finely dissect cellular heterogeneity within populations previously defined by "bulk" assays and uncover rare cell types. In human hematopoiesis, megakaryocytes erythroid cells differentiate from a shared precursor, megakaryocyte-erythroid progenitor (MEP), which remains poorly defined.To clarify pathway erythro-megakaryocyte differentiation, we correlate surface immunophenotype, transcriptional profile,...
Myelofibrosis is a severe myeloproliferative neoplasm characterized by increased numbers of abnormal bone marrow megakaryocytes that induce fibrosis, destroying the hematopoietic microenvironment. To determine cellular and molecular basis for aberrant megakaryopoiesis in myelofibrosis, we performed single-cell transcriptome profiling 135,929 CD34+ lineage− stem progenitor cells (HSPCs), proteomics, genomics, functional assays. We identified bias toward megakaryocyte differentiation apparent...
Human hematopoiesis is a dynamic process that starts in utero 18–21 days post-conception. Understanding the site- and stage-specific variation important if we are to understand origin of hematological disorders, many which occur at specific points human lifespan. To unravel how hematopoietic stem/progenitor cell (HSPC) compartment changes during ontogeny underlying gene regulatory mechanisms, compare 57,489 HSPCs from 5 different tissues spanning 4 developmental stages through lifetime....
Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid (aCML) are rare disorders that challenging with regard to diagnosis clinical management. To study the similarities differences between these disorders, we undertook a multicenter international of one largest case series (CNL, n = 24; aCML, 37 cases, respectively), focusing on mutational profiles (n 53 molecular data) diseases. We found no in presentations or outcomes both entities. As previously described, CNL aCML share...
Abstract Accurate diagnosis and classification of myeloproliferative neoplasms (MPNs) requires integration clinical, morphological, genetic findings. Despite major advances in our understanding the molecular basis MPNs, morphological assessment bone marrow trephines (BMT) is critical differentiating MPN subtypes their reactive mimics. However, heavily constrained by a reliance on subjective, qualitative, poorly reproducible criteria. To improve we have developed machine learning approach for...