A5044719954- Platelet Disorders and Treatments
- Extracellular vesicles in disease
- Neurogenesis and neuroplasticity mechanisms
- Mesenchymal stem cell research
- MicroRNA in disease regulation
- Blood transfusion and management
- Blood properties and coagulation
- Nuclear Structure and Function
- Antiplatelet Therapy and Cardiovascular Diseases
- Acute Myeloid Leukemia Research
- Periodontal Regeneration and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Blood groups and transfusion
- Immune cells in cancer
- Protease and Inhibitor Mechanisms
- Kruppel-like factors research
- Hematopoietic Stem Cell Transplantation
- Microfluidic and Bio-sensing Technologies
- 3D Printing in Biomedical Research
- Immune Cell Function and Interaction
- Blood donation and transfusion practices
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Cell Adhesion Molecules Research
- Erythrocyte Function and Pathophysiology
University of Cambridge
2018-2025
Wellcome/MRC Cambridge Stem Cell Institute
2019-2024
NHS Blood and Transplant
2021-2024
University of Helsinki
2024
Paracelsus Medical University
2024
Austral University of Chile
2024
University of Westminster
2024
National Health Service
2019-2022
Medical Research Council
2019-2022
Bridge University
2022
Hematopoietic stem cells (HSCs) residing in the bone marrow (BM) accumulate during aging but are functionally impaired. However, role of HSC-intrinsic and -extrinsic mechanisms remains debated. Megakaryocytes promote quiescence neighboring HSCs. Nonetheless, whether megakaryocyte-HSC interactions change pathological/natural is unclear. Premature Hutchinson-Gilford progeria syndrome recapitulates physiological features, these arise from altered or niche unknown. Here, we show that BM...
Adult hematopoietic stem cells (HSCs) are predominantly quiescent and can be activated in response to acute stress such as infection or cytotoxic insults. STAT1 is a pivotal downstream mediator of interferon (IFN) signaling required for IFN-induced HSC proliferation, but little known about the role regulating homeostatic stem/progenitor (HSPCs). Here, we show that loss altered steady state HSPC landscape, impaired function transplantation assays, delayed blood cell regeneration following...
Platelets, small hemostatic blood cells, are derived from megakaryocytes. Both bone marrow and lung principal sites of thrombopoiesis although underlying mechanisms remain unclear. Outside the body, however, our ability to generate large number functional platelets is poor. Here we show that perfusion megakaryocytes ex vivo through mouse vasculature generates substantial platelet numbers, up 3000 per megakaryocyte. Despite their size, able repeatedly passage vasculature, leading enucleation...
This series of illustrated capsules summarizes the presentations made by speakers at first International Advanced Course in Platelet Research held Murcia (Spain) from 27 to 28 September, 2024. is course receive a Fundamental Workshop Grant Society on Thrombosis and Haemostasis (ISTH) was also supported administratively scientifically Spanish (SETH). unique focused new methodologies applied platelet research how these are increasing our understanding formation, their multifunctionality...
Abstract The production of in vitro–derived platelets has great potential for transfusion medicine. Here, we build on our experience the forward programming (FoP) human pluripotent stem cells (hPSCs) to megakaryocytes (MKs) and address several aspects complex challenges bring this technology bedside. We first identify clinical-grade hPSC lines that generate MKs efficiently. design a bespoke media maximize both maturity improve platelet output. Crucially, transition lentiviral-based FoP hPSCs...
The process of platelet production has so far been understood to be a 2-stage process: megakaryocyte maturation from hematopoietic stem cells followed by proplatelet formation, with each phase regulating the peripheral blood count. Proplatelet formation releases into bloodstream beads-on-a-string preplatelets, which undergo fission mature platelets. For first time, we show that preplatelet is third, tightly regulated, critical akin cytokinesis regulates We deficiency in cytokine...
Impaired healing is common in wounds infected with the major human pathogen Staphylococcus aureus, although underlying mechanisms are poorly understood. Here, we show that S. aureus lipoteichoic acid (LTA) inhibits platelet aggregation caused by physiological agonists and reduced thrombus formation vitro. The presence of D-alanine on LTA necessary for full inhibitory effect. Inhibition was blocked using a monoclonal anti-platelet activating factor receptor (PafR) antibody Ginkgolide B,...
Neonatal haemorrhaging is often co-observed with thrombocytopenia; however, no evidence of a causal relationship low platelet count has been reported. Regardless, the administration transfusion based upon this parameter. Accurate measurement function in small volumes adult blood samples by flow cytometry well established and we propose that use same technology could provide complementary information to guide transfusions premature neonates.In 28 neonates born at 27-41 weeks gestation, after...
Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present chronic non-remyelinated lesions MS and an increase circulating platelets has been described experimental autoimmune encephalomyelitis (EAE) mice, animal model MS. However, contribution remains unexplored. Here we show platelet aggregation proximity OPCs areas demyelination....
Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present chronic non-remyelinated lesions MS and an increase circulating platelets has been described experimental autoimmune encephalomyelitis (EAE) mice, animal model MS. However, contribution remains unexplored. Here we show platelet aggregation proximity OPCs areas demyelination....
Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present chronic non-remyelinated lesions MS and an increase circulating platelets has been described experimental autoimmune encephalomyelitis (EAE) mice, animal model MS. However, contribution remains unexplored. Here we show platelet aggregation proximity OPCs areas demyelination....
Infection by Staphylococcus aureus is the leading cause of infective endocarditis (IE). Activation platelets this pathogen results in their aggregation and thrombus formation which are considered to be important steps development pathogenesis IE. Here, we show that a secreted cysteine protease, staphopain A, activates human induces aggregation. The culture supernatant scpA mutant deficient A production was reduced its ability trigger platelet agonist activity purified inhibited staphostatin...
Abstract Platelets are small anucleate blood cells1,2 with critical roles in haemostasis, thrombosis, inflammation, vascularization, innate immunity and tissue regeneration3,4. In vitro-derived platelets, as an alternative to native attractive for fundamental research because of their rapid genetic tractability, vectors drug component delivery5 clinical platelet transfusion. At present, however, very low production rate, poor agonist responsiveness, major obstacles. formed by fragmentation...
Abstract Platelets, small hemostatic blood cells, are derived from megakaryocytes, although the generation process is not clear. Only numbers of platelets have been produced in systems outside body, where bone marrow and lung proposed as sites platelet generation. Here we show that perfusion megakaryocytes ex vivo through mouse vasculature generates very large platelets, up to 3,000 per megakaryocyte. Despite their size, were able repeatedly passage vasculature, leading enucleation...
Abstract Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present chronic non-remyelinated lesions MS and an increase circulating platelets has been described experimental autoimmune encephalomyelitis (EAE) mice, animal model MS. However, contribution remains unexplored. Here we show platelet aggregation proximity OPCs areas...
Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function and remyelination is important to optimise the development regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS an increase circulating platelets has been described experimental autoimmune encephalomyelitis (EAE) mice, animal model MS. However, contribution remains unexplored. Here we show platelet aggregation proximity OPCs areas demyelination....