A5007078301- Platelet Disorders and Treatments
- Antiplatelet Therapy and Cardiovascular Diseases
- Atherosclerosis and Cardiovascular Diseases
- Immune Cell Function and Interaction
- Venous Thromboembolism Diagnosis and Management
- Immunodeficiency and Autoimmune Disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Genetic Associations and Epidemiology
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Genomics and Rare Diseases
- Cystic Fibrosis Research Advances
- Lipid metabolism and disorders
- Advanced Neural Network Applications
- Medical Imaging and Pathology Studies
- Mast cells and histamine
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Blood transfusion and management
- Acute Ischemic Stroke Management
- Digital Imaging for Blood Diseases
- Endometrial and Cervical Cancer Treatments
- Genetic factors in colorectal cancer
- Heparin-Induced Thrombocytopenia and Thrombosis
- Blood donation and transfusion practices
- Myeloproliferative Neoplasms: Diagnosis and Treatment
University of Reading
2021-2025
University of Cambridge
2017-2023
NHS Blood and Transplant
2018-2021
National Health Service
2018-2021
Cambridge University Hospitals NHS Foundation Trust
2020
In combination with microspotting, whole-blood microfluidics can provide high-throughput information on multiple platelet functions in thrombus formation. Based assessment of the inter- and intra-subject variability parameters microspot-based formation, we aimed to determine factors contributing this variation. Blood samples from 94 genotyped healthy subjects were analyzed for conventional phenotyping: i.e. hematologic parameters, glycoprotein (GP) expression levels activation markers (24...
Abstract Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step realize GWAS potential in introduction precision medicine. Here we set out determine mechanisms underpinning variant association platelet quantitative using cell type-matched epigenomic data and promoter long-range interactions. We identify regulatory functions for 423 565 (75%) demonstrate, through ex vivo proof principle genome editing validation,...
There is renewed interest in the use of whole blood (WB) for resuscitation trauma patients. Platelet function stored WB compared to platelet concentrates not well established and was assessed vitro this study.Leucocyte-depleted cold-stored (CS-WB) prepared using a Terumo WB-SP Imuflex kit held at 2-6°C alongside: (A) UK standard pooled platelets 20-24°C (RT-PLTS), (B) (CS-PLTS), (C) platelet-rich plasma produced (CS-PRP), 21 days. A series assays were function.Platelet count retained 57 ±...
Objectives Platelet activation underpins thrombus formation in ischemic stroke. The active, dimeric form of platelet receptor glycoprotein (GP) VI plays key roles by binding ligands collagen and fibrin, leading to activation. We investigated whether patients presenting with stroke expressed more GPVI on their surface had active circulating platelets as measured P-selectin exposure. Methods 129 or hemorrhagic were recruited within 8h symptom onset. Whole blood was analyzed for...
Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell methods are often tailored to specific modalities or require manual interventions specify hyper-parameters different experimental settings. Here, we present multi-modality benchmark, comprising over 1500 labeled images derived from more than 50 diverse biological experiments. The top participants developed Transformer-based deep-learning algorithm that not only exceeds existing but...
Accurate and comprehensive assessment of platelet function across cohorts donors may be key to understanding the risk thrombotic events associated with cardiovascular disease, and, hence, help personalize application antiplatelet drugs. However, tests can difficult perform analyze; they also unreliable or uninformative poorly standardized studies. The Platelet Phenomic Analysis (PPAnalysis) assay open-source software platform were developed in response these challenges. PPAnalysis utilizes...
Megakaryocytes (MKs) originate from cells immuno-phenotypically indistinguishable hematopoietic stem (HSCs), bypassing intermediate progenitors. They mature within the adult bone marrow and release platelets into circulation. Until now, there have been no transcriptional studies of primary human MKs.To characterize MKs HSCs using single-cell RNA sequencing, to investigate MK lineage commitment, maturation steps, thrombopoiesis.We show that at different levels polyploidization exhibit...
Abstract Platelets mediate arterial thrombosis, a leading cause of myocardial infarction and stroke. During injury, platelets adhere spread over exposed subendothelial matrix substrates the damaged blood vessel wall. The mechanisms which govern platelet activation their interaction with range are therefore regularly investigated using spreading assays. These assays often use differential interference contrast (DIC) microscopy to assess morphology analysis performed manual annotation. Here,...
Abstract The interindividual variation in the functional response of platelets to activation by agonists is heritable. Genome-wide association studies (GWASs) quantitative measures platelet function have identified fewer than 20 distinctly associated variants, some with unknown mechanisms. Here, we report GWASs pathway-specific responses agonism adenosine 5′-diphosphate, a glycoprotein VI–specific collagen mimetic, and thrombin receptor-agonist peptides, each specific 1 G protein–coupled...
Genetic studies of platelet reactivity (PR) phenotypes may identify novel antiplatelet drug targets. However, such have been limited by small sample sizes (n < 5000) because the complexity measuring PR. We trained a model to predict PR from complete blood count (CBC) scattergrams. A genome-wide association study this phenotype in 29 806 donors identified 21 distinct associations implicating 20 genes, which 6 previously. The effect size estimates were significantly correlated with flow...
Abstract Background This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature. Methods/results We combined classic plasma biochemistry biomarkers transcriptional epigenetic characterisation cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese lipodystrophy) lean individuals to identify molecular mechanisms play, highlighting patterns...
Introduction Atrial fibrillation (AF) increases the risk of ischemic stroke (IS). We hypothesized that functional form platelet receptor glycoprotein (GP) VI, GPVI-dimer, which binds to collagen and fibrin causing activation, is overexpressed in patients with AF who have not had a stroke. Methods A total 75 inpatients were recruited. None admitted or previously thrombotic events, including IS myocardial infarction. Platelet surface expression GPVI, activation marker P-selectin quantitated by...
<h3>Abstract</h3> Infections by nonsegmented negative-strand RNA viruses (NNSV) are widely thought to entail gradient gene expression from the well-established existence of a single promoter at 3’ end viral genome and assumption constant transcriptional attenuation between genes. But multiple recent studies show mRNA levels in infections respiratory syncytial virus (RSV), major human pathogen member NNSV, that inconsistent with simple gradient. Here we integrate known newly predicted...
Abstract In the current understanding of adult bone marrow hematopoiesis, megakaryocytes (MKs) originate from cells immuno-phenotypically indistinguishable hematopoietic stem (HSCs), bypassing intermediate progenitors. Here, we use single cell RNA sequencing to characterize HSCs and MKs human marrow, investigate MK lineage commitment maturation. We identify two primed HSC clusters exhibiting unique differentiation kinetics, at least one which is used in steady state stress thrombopoiesis. By...
Abstract Improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis are ongoing healthcare challenges. Using plasma biomarkers analysis coupled transcriptional epigenetic characterisation cell types involved in thrombosis, obtained from two extreme phenotype groups (obese lipodystrophy) comparing these to lean individuals blood donors, present study identifies molecular mechanisms at play, highlighting patterns abnormal activation innate...
Abstract Genetic studies of platelet reactivity (PR) phenotypes may identify novel antiplatelet drug targets. However, discoveries have been limited by small sample sizes ( n <5,000) due to the complexity measuring PR. We trained a model predict PR from complete blood count (CBC) scattergrams. A GWAS this phenotype in 29,806 donors identified 21 distinct associations implicating 20 genes, which six previously. The effect size estimates were significantly correlated with study...
Bone marrow residing hematopoietic stem cells provide lifelong blood homeostasis. In the current understanding of hematopoiesis HSCs all mature via a multipotent compartment and unipotent progenitors. Megakaryocytes are polyploid precursors that release platelets into bloodstream to maintain hemostasis. adult bone marrow, MKs exclusively originate from immuno-phenotypically in compartment, bypassing intermediate Here we used single cell RNA sequencing characterise human order investigate MK...