A5026763709- Erythrocyte Function and Pathophysiology
- Blood groups and transfusion
- Blood properties and coagulation
- Ion Transport and Channel Regulation
- Hemoglobinopathies and Related Disorders
- Neonatal Health and Biochemistry
- Pancreatic function and diabetes
- Phagocytosis and Immune Regulation
- Biomedical Research and Pathophysiology
- SARS-CoV-2 and COVID-19 Research
- Immune cells in cancer
- COVID-19 Clinical Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Amino Acid Enzymes and Metabolism
- Hematopoietic Stem Cell Transplantation
- Blood disorders and treatments
- SARS-CoV-2 detection and testing
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Malaria Research and Control
- RNA Interference and Gene Delivery
- Hemoglobin structure and function
- Pluripotent Stem Cells Research
- Signaling Pathways in Disease
- Cellular transport and secretion
University of Bristol
2016-2025
University of Antwerp
2025
National Institute for Health Research
2016-2024
Bristol Institute for Transfusion Sciences
2013-2022
NHS Blood and Transplant
2013-2022
National Health Service
2011-2020
Southmead Hospital
2011
Gènes, synapses et cognition
2008-2010
The Royal Free Hospital
2002-2007
University College London
2002-2007
Wound angiogenesis is an integral part of tissue repair and impaired in many pathologies healing. Here, we investigate the cellular interactions between innate immune cells endothelial at wounds that drive neoangiogenic sprouting real time vivo Our studies mouse zebrafish indicate macrophages are drawn to wound blood vessels soon after injury intimately associated throughout process macrophage ablation results neoangiogenesis. Macrophages also positively influence by driving resolution...
Abstract With increasing worldwide demand for safe blood, there is much interest in generating red blood cells vitro as an alternative clinical product. However, available methods generation of from adult and cord progenitors do not yet provide a sustainable supply, current systems using pluripotent stem generate viable cells. We have taken approach, immortalizing early erythroblasts stable line, which provides continuous supply The immortalized differentiate efficiently into mature,...
The study of human erythropoiesis in health and disease requires a robust culture system that consistently reliably generates large numbers immature erythroblasts can be induced to differentiate synchronously. We describe method modified from Leberbauer et al. (2005) obtain homogenous population peripheral blood mononuclear cells (PBMC) without prior purification CD34(+) cells. This pure expanded 4x10(8) 1x10(8) PBMC after 13-14 days culture. Upon synchronized differentiation, high levels...
The blood stage malaria parasite, the merozoite, has a small window of opportunity during which it must successfully target and invade human erythrocyte. process invasion is nonetheless remarkably rapid. To date, mechanistic models have focused predominantly on parasite actomyosin motor contribution to energetics entry. Here, we conducted numerical analysis using dimensions for an archetypal merozoite predict respective contributions host-parasite interactions invasion, in particular role...
Cord blood stem cells are an attractive starting source for the production of red in vitro therapy because additional expansion potential compared with adult peripheral progenitors and cord banks usually being more representative national populations than donors. Consequently, it is important to establish how similar RBCs cells. In this study, we used multiplex tandem mass tag labeling combined nano-LC-MS/MS compare proteome reticulocytes. 2838 unique proteins were identified, providing most...
Abstract Mitochondria and peroxisomes are closely related metabolic organelles, both in terms of origin function. can also be turned over by autophagy, processes termed mitophagy pexophagy, respectively. However, despite their close relationship, it is not known if organelles under similar conditions, so, how this might coordinated molecularly. Here, we find that multiple selective autophagy pathways activated upon iron chelation show pexophagy occur a BNIP3L/NIX‐dependent manner. We reveal...
Abstract Barth syndrome (BTHS) is a rare genetic disease caused by mutations in the TAFAZZIN gene. It characterized neutropenia, cardiomyopathy and skeletal myopathy. Neutropenia BTHS associated with life-threatening infections, yet there little understanding of molecular physiological causes this phenomenon. We combined bone marrow analysis, CRISPR/Cas9 genome editing hematopoietic stem cells functional characterization circulating patient neutrophils to investigate role their progenitors....
We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) deletion Val(850) (DeltaV850). The mutationsA858D DeltaV850 are novel; all seem to berestricted South-East Asian populations. Asianovalocytosis (SAO), resulting band residues400-408, occurred many but did not itselfresult dRTA. Compound heterozygotes each dRTA...
The classical central macrophage found in erythroblastic islands plays an important role erythroblast differentiation, proliferation and enucleation the bone marrow. Convenient human vitro models to facilitate study of erythroid-macrophage interactions are desired. Recently, we demonstrated that cultured monocytes/macrophages enhance erythropoiesis by supporting hematopoietic stem progenitor cell survival. Herein, describe these specific macrophages also support erythropoiesis. Human...
CRISPR-based DNA editing technologies enable rapid and accessible genome engineering of eukaryotic cells. However, the delivery genetically encoded CRISPR components remains challenging sustained Cas9 expression correlates with higher off-target activities, which can be reduced via Cas9-protein delivery. Here we demonstrate that baculovirus, alongside its cargo, used to package deliver proteins human Using protein-loaded baculovirus (pBV), or base editors proteins, leading efficient in By...
Distal renal tubular acidosis (dRTA) is characterised by defective acid secretion kidney α-intercalated cells. Some dominantly inherited forms of dRTA result from anion exchanger 1 (AE1) mutations. We have developed a stably transfected cell model for the expression human AE1 (kAE1) and mutant kAE1 proteins in MDCKI Normal was delivered to plasma membrane non-polarised cells basolateral polarised The N-glycan processed complex form. Surprisingly, increased permeability paracellular barrier...
The human electrogenic renal Na-HCO(3) cotransporter (NBCe1-A; SLC4A4) is localized to the basolateral membrane of proximal tubule cells. Mutations in SLC4A4 gene cause an autosomal recessive tubular acidosis (pRTA), a disease characterized by impaired ability reabsorb HCO(3)(-) from glomerular filtrate. Other symptoms can include mental retardation and ocular abnormalities. Recently, novel homozygous missense mutant (R881C) NBCe1-A was reported patient with severe pRTA phenotype. protein...
Report26 April 2018Open Access Transparent process Enhancement of red blood cell transfusion compatibility using CRISPR-mediated erythroblast gene editing Joseph Hawksworth School Biochemistry, University Bristol, UK Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Search more papers by this author Timothy J Satchwell NIHR Research Unit, Marjolein Meinders Deborah E Daniels Fiona Regan Imperial College Healthcare NHS Trust, London, &...
Induced pluripotent stem cells (iPSC) are an attractive progenitor source for the generation of in vitro blood products. However, before iPSC-derived erythroid can be considered therapeutic use their similarity to adult must confirmed. We have analysed proteome differentiated from iPSC fibroblast derived line (C19) and showed they express hallmark RBC proteins, including all those ankyrin 4.1R complex. next compared three lines (C19, OCE1, OPM2) with that cord progenitors. Of 1989 proteins...
Severe COVID-19 appears rare in children. This is unexpected, especially young infants, who are vulnerable to severe disease caused by other respiratory viruses. We evaluate convalescent immune responses 4 infants under 3 months old with confirmed presented mild febrile illness, alongside their parents, and adult controls recovered from COVID-19. Although not statistically significant, compared seropositive adults, have high serum levels of IgG IgA SARS-CoV-2 spike protein, a corresponding...
Abstract Background Saliva is easily obtainable non-invasively and potentially suitable for detecting both current previous SARS-CoV-2 infection, but there limited evidence on the utility of salivary antibody testing community surveillance. Methods We established 6 ELISAs IgA IgG antibodies to whole spike protein, its receptor binding domain region nucleocapsid protein in saliva. evaluated diagnostic performance, using paired saliva serum samples, correlated mucosal systemic responses. The...
Enucleation is the step in erythroid terminal differentiation when nucleus expelled from developing erythroblasts creating reticulocytes and free nuclei surrounded by plasma membrane. We have studied protein sorting during human erythroblast enucleation using fluorescence activated cell (FACS) to obtain pure populations of produced vitro culture. Nano LC mass spectrometry was first used determine distribution profile obtained purified reticulocyte extruded populations. In general...
Despite the identification of high-incidence red cell antigen Era nearly 40 years ago, molecular background this antigen, together with other 2 members Er blood group collection, has yet to be elucidated. Whole exome and Sanger sequencing individuals serologically defined alloantibodies identified several missense mutations within PIEZO1 gene, encoding amino acid substitutions extracellular domain Piezo1 mechanosensor ion channel. Confirmation as carrier molecule for antigens was...
Macrophages have previously been characterized based on phenotypical and functional differences into suggested simplified subtypes of MØ, M1, M2a M2c. These macrophage can be generated in a well-established primary monocyte culture model that produces cells expressing accepted subtype surface markers. To determine how these retain similarities better understand their formation, we all four from the same donors. Comparative whole-cell proteomics confirmed distinct could induced donor...
Abstract Background Neutrophils are granulocytes with essential antimicrobial effector functions and short lifespans. During infection or sterile inflammation, emergency granulopoiesis leads to release of immature neutrophils from the bone marrow, serving boost circulating neutrophil counts. Steady state incompletely understood, partly due a lack genetically amenable models development. Methods We optimised method for ex vivo production human CD34 + haematopoietic progenitors. Using flow...