A5062786810- Platelet Disorders and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Antiplatelet Therapy and Cardiovascular Diseases
- Angiogenesis and VEGF in Cancer
- Advanced biosensing and bioanalysis techniques
- Diabetes Treatment and Management
- Advanced Glycation End Products research
- Cell Adhesion Molecules Research
- Advanced Biosensing Techniques and Applications
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Nitric Oxide and Endothelin Effects
- Protease and Inhibitor Mechanisms
- Periodontal Regeneration and Treatments
- Mast cells and histamine
- Blood Coagulation and Thrombosis Mechanisms
- Extracellular vesicles in disease
- Advanced Proteomics Techniques and Applications
- Inflammatory Biomarkers in Disease Prognosis
- Ion channel regulation and function
- Adipokines, Inflammation, and Metabolic Diseases
- Cellular Mechanics and Interactions
- Monoclonal and Polyclonal Antibodies Research
Hull York Medical School
2022-2025
University of Exeter
2017-2025
University of Hull
2024-2025
University Medical Center Hamburg-Eppendorf
2020-2024
Universität Hamburg
2020-2024
King's College London
2008-2021
International Neuromodulation Society
2018
University of Bath
2012-2017
University of Pavia
2015
University of Manchester
2010
Coagulopathy and inflammation are hallmarks of Coronavirus disease 2019 (COVID-19) associated with increased mortality. Clinical experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19 disease. The mechanisms that drive thrombo-inflammation poorly understood.
Endothelial progenitor cell (EPC) cultures and colony-forming units (CFUs) have been extensively studied for their therapeutic diagnostic potential. Recent data suggest a role EPCs in the release of proangiogenic factors. To identify factors secreted by EPCs, conditioned medium from EPC CFUs was analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometer combined with offline peptide separation nanoflow liquid chromatography. Results were verified...
Abstract Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from platelets able to support proliferation endothelial colony forming cells (ECFCs) in 2D cultures formation microvascular network vitro 3D cultures. Existing preparations require addition high concentrations recombinant growth factors allow only limited capillary-like structures. Additional...
NADPH oxidases (NOXs) contribute to platelet activation by a largely unknown mechanism. Here, we studied the effect of novel NOX inhibitor 2-acetylphenothiazine (2-APT) on human functional responses and intracellular signaling pathways.The generation superoxide ions was assessed single cell imaging adhering platelets using dihydroethidium (DHE), while other reactive oxygen species (ROS) were detected with 5-(and-6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate (CM-H(2)-DCFDA). Whole...
Abstract Contact activation refers to the process of surface-induced factor XII (FXII), which initiates blood coagulation and is captured by activated partial thromboplastin time (aPTT) assay. Here, we show mechanism diagnostic implications FXII contact activation. Screening recombinant mutants identified a continuous stretch residues Gln317–Ser339 that was essential for surface binding activation, thrombin generation coagulation. Peptides spanning these 23 competed with Although lacking...
At present, little is known regarding the mechanism of metabotropic glutamate receptor (mGluR) trafficking. To facilitate this characterization we inserted a haemagglutinin (HA) epitope tag in extracellular N‐terminal domain rat mGluR1a. In human embryonic kidney cells (HEK293), transiently transfected with HA‐mGluR1a, epitope‐tagged was primarily localized to cell surface prior agonist stimulation. Following stimulation (10 µ m ; 30 min) HA‐mGluR1a underwent internalization endosomes....
VASP (vasodilator-stimulated phosphoprotein) is an actin- and profilin-binding protein that expressed in platelets at high levels plays a major role negatively regulating secretory adhesive events these cells. substrate for cAMP- cGMP-regulated kinases it has been shown to be directly phosphorylated on Ser157 by PKC (protein kinase C). In the present paper, we show that, human platelets, Ser157, but not Ser239, response phorbol ester stimulation, manner blocked inhibitor BIM I...
Alzheimer's disease is associated with the accumulation of Aβ (amyloid β)-peptides in brain. Besides their cytotoxic effect on neurons, Aβ-peptides are thought to be responsible for atherothrombotic complications disease, which collectively known as cerebrovascular disease. In present study, we investigated human platelet signal transduction and function. We discovered that 25-35 domain induce an increase intracellular Ca2+ stimulates α-granule dense granule secretion leads release secondary...
Abstract Cell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex essential Arp2/3 mediated lamellipodia formation during mesenchymal cell several coinciding signals activate it. However, so far, no direct negative regulators are known. Here we identify Nance-Horan Syndrome-like 1 protein (NHSL1) as a binding partner of the complex, which co-localise at protruding lamellipodia. This interaction by Abi SH3 domain two sites in...
In the vascular system, pathological conditions that cause hypoxia are associated with increased platelet activity and thrombosis. Using a spreading assay, we show severe (i.e., 1%), venous 5%), and, surprisingly, arterial 12%) oxygen concentrations significant reduction in surface area coverage on fibrinogen comparison to atmospheric condition 21% oxygen), whilst adhesion collagen CRP were not affected. Importantly, addition of thrombin or zinc restored full fibrinogen, indicating...
There is a high degree of cross-talk between tyrosine phosphorylation and the serine/threonine signaling pathways. Here we show physical functional interaction classical protein kinase C isoform (cPKC), PKCalpha, two major nonreceptor kinases in platelets, Syk Src. In presence cPKC-selective inhibitor Go6976, platelet 5-hydroxytryptamine release was abolished response to co-activation glycoproteins VI Ib-IX-V by snake venom alboaggregin A, whereas aggregation substantially inhibited. Of...
Abstract Phosphorylation by kinases is an important post-translational modification of proteins. It a critical control for the regulation vital cellular activities and its dysregulation implicated in several diseases. A common drug discovery approach involves, therefore, time-consuming screenings large libraries candidate compounds to identify novel inhibitors protein kinases. In this work, we propose method that combines localized surface plasmon resonance (LSPR) electrolyte insulator...
Aims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human Results: Live cell imaging, electron paramagnetic resonance, pull-down dRP-interacting proteins, followed immunoblotting, gene silencing different NADPH oxidases (NOXs), their regulatory cosubunits small interfering RNA (siRNA) transfection,...
The progression of Alzheimer’s dementia is associated with neurovasculature impairment, which includes inflammation, microthromboses, and reduced cerebral blood flow. Here, we investigate the effects β amyloid peptides on function platelets, cells driving haemostasis. Amyloid peptide 1-42 (A 1-42), A 1-40, 25-35 were tested in static adhesion experiments, it was found that platelets preferentially adhere to compared other peptides. In addition, significant platelet spreading observed over...
Platelets release platelet-derived extracellular vesicles (PDEVs) upon activation - in a process that is regulated by generation of reactive oxygen species (ROS). Platelet NADPH oxidase-1 (Nox-1) contributes to ROS and thrombus formation downstream the collagen receptor GPVI.We aimed investigate whether PDEVs contain Nox-1 this relevant for PDEV-induced platelet activation.PDEVs were isolated through serial centrifugation after with thrombin agonist TRAP-6 (activated PDEVs) or absence...