A5083637761- Platelet Disorders and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Adenosine and Purinergic Signaling
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Nutrition, Genetics, and Disease
- Chronic Lymphocytic Leukemia Research
- Molecular Biology Techniques and Applications
- Cell Adhesion Molecules Research
- Pharmacological Effects of Natural Compounds
- Antiplatelet Therapy and Cardiovascular Diseases
- Blood Coagulation and Thrombosis Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Biotin and Related Studies
- Lipid metabolism and disorders
- RNA Research and Splicing
- Medicinal Plants and Bioactive Compounds
- Venous Thromboembolism Diagnosis and Management
- Wnt/β-catenin signaling in development and cancer
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Primary Care and Health Outcomes
- Mast cells and histamine
- Blood properties and coagulation
Massachusetts Institute of Technology
2025
Cincinnati Children's Hospital Medical Center
2025
MRC University of Glasgow Centre for Virus Research
2024
The University of Western Australia
2023
UK Research and Innovation
2023
Medical Research Council
2023
University of Bristol
2013-2023
University College London
2014-2022
Northern Devon Healthcare NHS Trust
2022
University College London Hospitals NHS Foundation Trust
2022
Glycogen synthase kinase-3 is a Ser/Thr kinase, tonically active in resting cells but inhibited by phosphorylation of an N-terminal Ser residue (Ser(21) GSK3α and Ser(9) GSK3β) response to varied external stimuli. Recent work suggests that GSK3 functions as negative regulator platelet function, how regulated platelets has not been examined detail. Here, we show early thrombin-mediated (0-30 s) was blocked PKC inhibitors largely absent from PKCα knock-out mice. In contrast, late (2-5 min)...
Abstract P2X7 receptors (P2X7Rs) are ATP-gated ion channels that trigger caspase-1 activation in the presence of TLR ligands. Inflammatory is responsible for proteolytic IL-1β. However, signaling events couple P2X7Rs to remain undefined. In this study we demonstrate ATP-induced cellular oxidation critical and subsequent IL-1β processing. Purinergic receptor stimulation, including P2X7Rs, endotoxin-primed human monocytes augments NADPH oxidase activity whereas concurrent purinergic...
Protein kinase B (PKB, Akt) is a Ser/Thr involved in the regulation of cell survival, proliferation, and metabolism activated by dual phosphorylation on Thr308 activation loop Ser473 hydrophobic motif. It plays contributory role to platelet function, although little known about its regulation. In this study, we investigated mammalian target rapamycin complex (mTORC)-2 Akt using recently identified small molecule ATP competitive mTOR inhibitors PP242 Torin1. Both Torin1 blocked thrombin...
The phagocytic NADPH oxidase (NOX2) plays a fundamental role in host defense and innate immunity. Here we demonstrate that external ATP triggers rapid cellular oxidation inhibited by diphenyleneiodonium endotoxin-primed J774 macrophages primary murine bone marrow-derived macrophages. To identify the source of reactive oxygen species (ROS), compared responses between wild-type NOX2-deficient ATP-mediated ROS production was strongly attenuated where were comparable to inhibition with...
AimsPatients with conditions that are associated insulin resistance such as obesity, type 2 diabetes mellitus, and polycystic ovary syndrome have an increased risk of thrombosis a concurrent hyperactive platelet phenotype. Our aim was to determine whether megakaryocytes/platelets promotes hyperactivation.
RNA is a central molecule for viruses; however, the interactions that viral (vRNA) establishes with host cell only starting to be elucidated. Here, we determine ribonucleoprotein (RNP) composition of prototypical arthropod-borne Sindbis virus (SINV). We show SINV RNAs engage hundreds cellular proteins, including group nuclear RNA-binding proteins (RBPs) unknown roles in infection. demonstrate these RBPs are selectively translocated cytoplasm after infection, where they accumulate replication...
Objective— Platelet hyperactivity is a contributing factor in the pathogenesis of cardiovascular disease and can be induced by elevated levels circulating growth factors, such as insulin-like factor-1 (IGF-1). IGF-1 primer that cannot stimulate platelet activation itself, but combination with physiological stimuli potentiate functional responses via phosphoinositide 3-kinase–dependent mechanism. In this study, we explored role 3-kinase p110α isoform IGF-1–mediated enhancement function....
Key Points We present the first in-depth analysis of platelet PtdIns(3,4,5)P3-binding proteins, providing a valuable resource for future studies. The protein, DAPP1, negatively regulates glycoprotein VI–driven activation and thrombus formation.
In response to collagen stimulation, platelets use a coordinated system of fluid entry undergo membrane ballooning, procoagulant spreading, and microvesiculation. We hypothesized that water was mediated by the channel aquaporin-1 (AQP1) aimed determine its role in platelet thrombosis. established human mouse express AQP1 localize internal tubular structures. However, deletion had minimal effects on collagen-induced granule secretion, aggregation, or ballooning. Conversely, microvesiculation,...
ABSTRACT Pulmonary hypertension (PH) is a rare, complex disease affecting both children and adults. Efforts to provide health education are imperative as literacy impacts patient caregiver capacity acquire, process, understand information make informed decisions. The current study sought family perception of “Hank the Heart”, an animation used for enhancing literacy, preferred learning methods future educational preferences. A qualitative was conducted assess Heart” using focus groups...
Aspirin and P2Y12 antagonists are antiplatelet compounds that used clinically in patients with thrombosis. However, some 'resistant' to therapy, which increases their risk of developing acute coronary syndromes. These often present an underlying condition is associated altered levels circulating platelet primers hyperactivity. Platelet cannot stimulate activation, but, combination physiologic stimuli, significantly enhance function.To explore the role resistance evaluate whether...
Podocytes are crucial for preventing the passage of albumin into urine and, when lost, associated with development albuminuria, renal failure and cardiovascular disease. have limited capacity to regenerate, therefore pro-survival mechanisms critically important. Insulin-like growth factor-II (IGF-II) is a potent survival factor; however, its major function thought be in prenatal development, circulating levels high. IGF-II has only previously been reported continue expressed discrete regions...
Rapamycin, an inhibitor of mammalian target rapamycin complex-1 (mTORC1), reduces platelet spreading, thrombus stability, and clot retraction. Despite important role mTORC1 in function, little is known about how it regulated. The objective this study was to determine the signaling pathways that regulate human platelets.Mammalian activation assessed by measuring phosphorylation its downstream substrate ribosomal S6 kinase 1 (p70S6K).Thrombin or protein C (PKC) activator phorbal 12-myristate...
One of the mechanisms by which PI3 kinase can regulate platelet function is through phosphorylation downstream substrates, including glycogen synthase kinase-3 (GSK3)α and GSK3β. Platelet activation results in an N-terminal serine residue GSK3α (Ser21) GSK3β (Ser9), competitively inhibits substrate phosphorylation. However, role these paralogs still largely unknown. Here, we employed GSK3α/β phosphorylation-resistant mouse models to explore this inhibitory regulating activation. Expression...
Abstract Sphingosine 1-phosphate (S1P) is a bioactive signalling sphingolipid that increased in diseases such as obesity and diabetes. S1P can modulate platelet function, however the direction of effect receptors (S1PRs) involved are controversial. Here we describe role regulating human function identify receptor subtypes responsible for priming. Human platelets were treated with protease-activated 1 (PAR-1)-activating peptide presence or absence S1P, S1PR agonists antagonists, sphingosine...
Abstract Thrombopoietin (TPO) enhances platelet activation through of the tyrosine kinase; JAK2 and lipid kinase phosphatidylinositide 3-kinase (PI3K). The aim our study was to identify PI3K isoforms involved in mediating effect TPO on function elucidate underlying mechanism. We found that p110β plays an essential role TPO-mediated (i) priming protease-activated receptor (PAR)-mediated integrin α IIb β 3 α-granule secretion, (ii) synergistic enhancement PAR-mediated small GTPase RAP1, a...