A5074849755- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- CRISPR and Genetic Engineering
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- Iron Metabolism and Disorders
- Metabolism, Diabetes, and Cancer
- CNS Lymphoma Diagnosis and Treatment
- Glioma Diagnosis and Treatment
- CAR-T cell therapy research
- Genomics and Chromatin Dynamics
- Acute Lymphoblastic Leukemia research
- Prenatal Screening and Diagnostics
- RNA and protein synthesis mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Telomeres, Telomerase, and Senescence
- Heparin-Induced Thrombocytopenia and Thrombosis
- Trace Elements in Health
- Clinical practice guidelines implementation
- Acute Myeloid Leukemia Research
- Acute Ischemic Stroke Management
- Virus-based gene therapy research
- Intramuscular injections and effects
- Chronic Lymphocytic Leukemia Research
- Pancreatic function and diabetes
MRC Weatherall Institute of Molecular Medicine
2017-2025
University of Oxford
2017-2025
John Radcliffe Hospital
2019-2025
Queen Mary University of London
2024-2025
Barts Health NHS Trust
2015-2024
Imperial College Healthcare NHS Trust
2023
St Mary's Hospital
2023
St. Mary's Hospital
2023
Medical Research Council
2017-2020
Creative Electron (United States)
2018
β-Thalassemia is one of the most common inherited anemias, with no effective cure for patients. The pathophysiology reflects an imbalance between α- and β-globin chains excess free α-globin causing ineffective erythropoiesis hemolysis. When α-thalassemia co-inherited β-thalassemia, are reduced significantly ameliorating clinical severity. Here we demonstrate use CRISPR/Cas9 genome editing primary human hematopoietic stem/progenitor (CD34+) cells to emulate a natural mutation, which deletes...
Haemoglobin E (HbE) β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE is due a point mutation in codon 26 the human HBB gene on one allele (GAG; glutamatic acid → AAG; lysine, E26K), and any causing other. When inherited together compound heterozygosity these mutations can cause thalassaemic phenotype. However, if only mutated individuals are carriers for respective have an asymptomatic phenotype (β-thalassaemia...
Red blood cell development from erythroid progenitors requires profound reshaping of metabolism and gene expression. How these transcriptional metabolic alterations are coupled is unclear. Nprl3 (an inhibitor mTORC1) has remained in synteny with the α-globin genes for >500 million years, harbours most a-globin enhancers. However, whether serves an role unknown. We found that while haematopoietic require basal expression, expression further boosted by This lineage-specific upregulation...
Diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL) is a rare condition carrying poor prognosis. No optimal therapeutic regimen has been identified. We retrospectively analysed 23 patients SCNS-DLBCL treated R-IDARAM (rituximab 375 mg/m(2) IV day 1; methotrexate 12·5 mg by intrathecal injection idarubicin 10 /day days 1 and 2; dexamethasone 100 mg/day infusion over 12 h 1-3; cytosine arabinoside 1000 2000 2 3. Ten out (44%) had CNS at initial...
Abstract Generation of mature cells from progenitors requires tight coupling differentiation and metabolism. During erythropoiesis, erythroblasts are required to massively upregulate globin synthesis then clear extraneous material enucleate produce erythrocytes 1–3 . Nprl3 has remained in synteny with the α-globin genes for >500 million years 4 , harbours majority enhancers 5 is a highly conserved inhibitor mTORC1, which controls cellular However, whether itself serves an erythroid role...
Nil.
Development of red blood cells from progenitors requires profound reshaping both gene expression and metabolism. How these processes are coupled is unclear. Nprl3, an inhibitor mTORC1, has remained in synteny with α-globin for >500 million years, harbours enhancers. We show that Nprl3 promoter-deleted mice, which retain all enhancers, exhibit severe erythropoietic-specific developmental defects. Loss disrupts autophagy, glycolysis redox control, required to complete erythropoiesis. Human...
MRC Weatherall Institute of Molecular Medicine, University Oxford, UK This is an open access Abstract Book distributed under the Attribution-NonCommercial-NoDerivs (CCBY-NC-ND), which allows third parties to download abstracts and share them with others as long they credit author abstract book, but cannot change content in any way or use commercially. http://creativecommons.org/licenses/by-nc-nd/4.0
Aims: HbE/β-thalassemia is the commonest form of severe β-thalassemia, and comprises approximately 50% all cases worldwide1. caused by HbE codon 26 G>A mutation on one allele any β0-thalassemia other. There a reduction in β-globin production, resulting relative excess α-globin chains that leads to ineffective erythropoiesis. Importantly, individuals with one, but not two, alleles have β-thalassemia trait, carrier state normal phenotype shared 1.5% world’s population2. Recent gene therapy...