A5066992499- Hemoglobinopathies and Related Disorders
- Blood groups and transfusion
- Iron Metabolism and Disorders
- Erythrocyte Function and Pathophysiology
- Prenatal Screening and Diagnostics
- Immunodeficiency and Autoimmune Disorders
- Complement system in diseases
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Mosquito-borne diseases and control
- Neonatal Health and Biochemistry
- Malaria Research and Control
- Otitis Media and Relapsing Polychondritis
- CRISPR and Genetic Engineering
- Blood properties and coagulation
- Mitochondrial Function and Pathology
- Peroxisome Proliferator-Activated Receptors
- Autopsy Techniques and Outcomes
- MicroRNA in disease regulation
- Cardiac Health and Mental Health
- Inflammasome and immune disorders
- Sex and Gender in Healthcare
- Abdominal Trauma and Injuries
- Genomic variations and chromosomal abnormalities
- Cardiac Fibrosis and Remodeling
King's College London
2021-2025
Inserm
2016-2025
Institut des Maladies Génétiques Imagine
2024
London Cancer
2023
Hadassah Medical Center
2016-2022
King's College Hospital
2022
Laboratory of Excellence GR-Ex
2017-2021
Institut National de la Transfusion Sanguine
2018-2021
Biologie Intégrée du Globule Rouge
2016-2020
Université Paris Cité
2016-2020
While ineffective erythropoiesis has long been recognized as a key contributor to anemia in thalassemia, its role of sickle cell disease (SCD) not critically explored. Using vitro and vivo derived human erythroblasts we assessed the extent SCD. Modeling bone marrow hypoxic environment, found that hypoxia induces death starting at polychromatic stage, positively selecting cells with high levels fetal hemoglobin (HbF). Cell was associated cytoplasmic sequestration heat shock protein 70 rescued...
Vivax malaria has long been thought to be absent from sub-Saharan Africa owing the high proportion of individuals lacking Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein (PvDBP) and DARC is assumed main pathway used by merozoites invade reticulocytes. However, increasing number reports cases genotypically Duffy-negative (DN) raised questions regarding invasion pathway(s). Here, we show that a subset DN erythroblasts...
Abstract Spleen dysfunction is central to morbidity and mortality in children with sickle cell anemia (SCA). The initiation determinants of spleen injury, including acute splenic sequestration (ASS) have not been established. We investigated function longitudinally a cohort 57 infants SCA enrolled at 3 6 months age followed up 24 explored the respective contribution decreased red blood (RBC) deformability increased RBC adhesion on ASS. was evaluated by sequential 99mTc heated scintigraphy...
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The human red blood cell is a biconcave disc of 6-8 × 2 μm that highly elastic. This capacity to deform enables it stretch while circulating through narrow capillaries ensure its main function gas exchange. Red shape and deformability are altered in membrane disorders because defects skeletal or proteins affecting protein-protein interactions. properties also other pathologies such as sickle disease. Sickle disease genetic hereditary disorder caused by single point mutation the β-globin gene...
α-Thalassemia is one of the most important genetic modulators sickle cell disease (SCD). Both beneficial and detrimental effects have been described previously. We use a 12-year data set on large cohort patients with HbSS (n = 411) HbSC 146) to examine wide range these clinical laboratory associations. Our novel findings are that α-thalassemia strongly reduces erythrocyte potassium chloride co-transporter (KCC) activity in both (p .035 p .00045 respectively), suggesting mechanism through...
Abstract In order to identify very early prognostic factors that can provide insights into subsequent clinical complications, we performed a comprehensive longitudinal multi‐center cohort study on 57 infants with sickle cell anemia (55 SS; 2 Sβ°) during the first years of life ( ClinicalTrials.gov : NCT01207037). Time occurrence severe event—acute splenic sequestration (ASS), vaso‐occlusive (VOC) event requiring hospitalization, transfusion requirement, conditional/ abnormal cerebral...
Abstract While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to red blood (RBC) turnover, SCA is specifically characterized by susceptibility infections. In this study, histological lesions in the spleens pediatric patients with were analyzed, close correlation past clinical history comparatively HS, healthy transfused β‐thalassemia (TDT). An evaluation pulp elementary (red fibrosis, iron deposition, number...
Painful vaso-occlusive crisis (VOC) represents the most frequent complication encountered by patients with sickle cell anaemia (SCA). In animal models, increased red blood (RBC) adhesion to endothelium has been demonstrated initiate VOC increasing RBC transit time through microcirculation, predisposing them sickling and occluding vessels (Kaul et al, 1996). Correlation between disease severity reported (Hebbel 1980) are characterized viscosity compared few (Connes 2016). However, while...
Vaso-occlusive crises are the hallmark of sickle cell disease (SCD). They believed to occur in two steps, starting with adhesion deformable low-dense red blood cells (RBCs), or other such as neutrophils, wall post-capillary venules, followed by trapping denser RBCs leukocytes areas because reduced effective lumen-diameter. In SCD, heterogeneous terms density, shape, deformability and surface proteins, which accounts for differences observed their resistance shear stress. Sickle exhibit...
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Although the protease inhibitor (PI) Lopimune has proven to be effective, no studies have examined side effects of on mitochondrial bioenergetics in hepatocytes. The objective present study is evaluate respiration, production reactive oxygen species (ROS) and expression uncoupling protein-2 (UCP2) mouse hepatocytes following administration. Mitochondria were extracted from liver using differential centrifugation isolated by collagenase perfusion procedure. Mitochondrial respiration was...
This commentary discusses the therapeutic potential of drug repurposing in sickle cell disease, highlighting efficacy hydroxyurea enhancing fetal haemoglobin and work Raz et al. discussing using memantine for improving cognitive function, while emphasizing need further research. Commentary on: Memantine treatment disease: A 1‐year study its effects on functions neural processing. Br J Haematol 2024 (Online ahead print). doi: 10.1111/bjh.19866 .
Abstract VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently discovered autoinflammatory disorder linked to somatic mutations in the UBA1 gene, resulting profound cytoplasm-restricted defect ubiquitylation. The disease characterized by macrocytic anemia that remains poorly understood. To investigate erythroid lineage VEXAS, we conducted comprehensive study combining vivo assessments of patients’ mature red cells and marrow erythroblasts, alongside vitro...