A5026966620- Platelet Disorders and Treatments
- Acute Myeloid Leukemia Research
- Hematological disorders and diagnostics
- Cancer, Hypoxia, and Metabolism
- Antiplatelet Therapy and Cardiovascular Diseases
- Blood properties and coagulation
- Venous Thromboembolism Diagnosis and Management
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Heme Oxygenase-1 and Carbon Monoxide
- Lung Cancer Treatments and Mutations
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Advanced Biosensing Techniques and Applications
- Medical Imaging and Pathology Studies
- Blood groups and transfusion
- Neonatal Health and Biochemistry
- Hemoglobinopathies and Related Disorders
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Vasculitis and related conditions
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Fibroblast Growth Factor Research
- Sepsis Diagnosis and Treatment
- Magnolia and Illicium research
University of Birmingham
2018-2024
Maastricht University Medical Centre
2022
Maastricht University
2018-2022
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 S100A8/A9, also known as “calprotectin” or “MRP8/14,” is an alarmin primarily secreted by activated myeloid cells with antimicrobial, proinflammatory, and prothrombotic properties. Increased plasma levels of S100A8/A9 in thrombo-inflammatory diseases are associated thrombotic complications. We assessed the presence lung autopsies from patients COVID-19 investigated molecular mechanism which affects platelet function thrombosis. were increased sustained high during hospitalization...
The role of glycoprotein VI (GPVI) in platelets was investigated 3 families bearing an insertion within the GP6 gene that introduces a premature stop codon prior to transmembrane domain, leading expression truncated protein cytoplasm devoid region. Western blotting and flow cytometry GP6hom (homozygous) confirmed loss full protein. level Fc receptor γ-chain, which associates with GPVI membrane, partially reduced, but other receptors signaling proteins not altered. Spreading on collagen von...
GPVI is the major signalling receptor for collagen on platelets. Dimerization of required binding and initiation through associated FcR-γ chain. Recently, fibrin fibrinogen have been identified as ligands shown to induce in support thrombus formation stabilization. Contrasting observations reported whether binds monomeric or dimeric GPVI, neither form. In this article, we discuss reasons contradictory results how reconcile these. We conclude that a lack structural knowledge regarding...
Losartan and honokiol are small molecules which have been described to inhibit aggregation of platelets by collagen. has proposed block clustering GPVI but not affect binding Honokiol reported bind directly only at a concentration that is three orders magnitude higher than needed for inhibition aggregation. The mechanism action both inhibitors so far unclear. In the present study, we confirm inhibitory effects agents on platelet collagen show also induced activation CLEC-2 or low affinity...
Fibrin is considered to strengthen thrombus formation via integrin αIIbβ3, but recent findings indicate that fibrin can also act as ligand for platelet glycoprotein VI. Approach and Results: To investigate the thrombus-forming potential of roles receptors herein, we generated a range immobilized surfaces, some which were cross-linked with factor XIIIa contained VWF-BP (von Willebrand factor-binding peptide). Multicolor microfluidics assays whole-blood flowed at high shear rate (1000 s-1)...
Understanding the pathways involved in formation and stability of core shell regions a platelet-rich arterial thrombus may result new ways to treat thrombosis. The distinguishing feature between these two is absence fibrin which indicates that vitro flow-based assays over thrombogenic surfaces, coagulation, can be used resemble this region. In study, we have investigated contribution Syk tyrosine kinase platelet aggregates (or thrombi) formed on collagen or atherosclerotic plaque homogenate...
Charge interactions play a critical role in the activation of innate immune system by damage- and pathogen-associated molecular pattern receptors. The ability these receptors to recognize wide spectrum ligands through common mechanism is host defense. In this article, we argue that platelet glycoprotein signal conserved tyrosine-based motifs function as recognition (PRRs) for charged endogenous exogenous ligands, including sulfated polysaccharides, proteins nanoparticles. This exemplified...
Low plasma levels of protein C or S are associated with venous thromboembolism rather than myocardial infarction. The high coagulant activity in patients thrombophilia a (familial) defect is explained by defective activation, involving thrombomodulin and S. This causes increased plasmatic thrombin generation.
Free labile hemin acts as a damage-associated molecular pattern during acute and chronic hemolysis muscle injury, supporting platelet activation thrombosis.
Abstract Sickle cell disease (SCD) leads to hemolytic anemia, vaso-occlusive crisis (VOC), hypoperfusion, and progressive organ damage. Hemin, released during hemolysis in SCD, induces platelet activation through CLEC-2, endothelial TLR4, neutrophil adhesion NETosis, all of which are regulated by spleen tyrosine kinase (Syk). In this study, we assessed recruitment the pulmonary, renal, splenic, hepatic microvasculature control SCD mice following hemin injection effect Syk inhibition on...
<div>Abstract<p>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...
<p>MM ALL Donor Details</p>
<p>Supplementary Materials and Methods, Supplementary Figures S1-S12</p>
<p>Supplementary Materials and Methods, Supplementary Figures S1-S12</p>
<p>Supplementary Table 7 NGS Panel</p>
<p>MM ALL Donor Details</p>
<p>Supplementary Table 2 Gene sets for GSEA</p>
<p>Supplementary Table 3 HD and MPN samples.</p>
<p>Supplementary Table 1 VEGFAC Top Differentially Expressed Genes by Cluster</p>
<p>Supplementary Table 1 VEGFAC Top Differentially Expressed Genes by Cluster</p>
<div>Abstract<p>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...