A5032647168- Glioma Diagnosis and Treatment
- Bioinformatics and Genomic Networks
- Prion Diseases and Protein Misfolding
- RNA Research and Splicing
- Barrier Structure and Function Studies
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Single-cell and spatial transcriptomics
- Circular RNAs in diseases
- Protein Degradation and Inhibitors
- Neuroinflammation and Neurodegeneration Mechanisms
- Alcoholism and Thiamine Deficiency
- Microtubule and mitosis dynamics
- Clusterin in disease pathology
- Cell Adhesion Molecules Research
- Neurological Disease Mechanisms and Treatments
- Biomarkers in Disease Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Chromatin Remodeling and Cancer
- Cardiac Ischemia and Reperfusion
- CRISPR and Genetic Engineering
- Skin and Cellular Biology Research
- Amino Acid Enzymes and Metabolism
- Anesthesia and Neurotoxicity Research
- FOXO transcription factor regulation
University College London
2013-2020
National Hospital for Neurology and Neurosurgery
2013-2020
Brain Tumour Research
2013
Queen's Medical Centre
2013
Queen Mary University of London
2013
Cerebral blood flow is reduced early in the onset of Alzheimer's disease (AD). Because most vascular resistance within brain capillaries, this could reflect dysfunction contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish relevance, rodent experiments define mechanism. found that humans with cognitive decline, amyloid β (Aβ) constricts capillaries at pericyte locations. This was caused by Aβ generating reactive oxygen species, which...
<b>Objectives</b> To carry out a further survey of archived appendix samples to understand better the differences between existing estimates prevalence subclinical infection with prions after bovine spongiform encephalopathy epizootic and see whether broader birth cohort was affected, implications for management blood products handling surgical instruments. <b>Design</b> Irreversibly unlinked anonymised large scale samples. <b>Setting</b> Archived from pathology departments 41 UK hospitals...
Abstract Widespread dietary exposure of the population Britain to bovine spongiform encephalopathy (BSE) prions in 1980s and 1990s led emergence variant Creutzfeldt-Jakob Disease (vCJD) humans. Two previous appendectomy sample surveys (Appendix-1 -2) estimated prevalence abnormal prion protein (PrP) British exposed BSE be 237 per million 493 million, respectively. The Appendix-3 survey was recommended measure PrP groups thought have been unexposed BSE. Immunohistochemistry for performed on...
Neuronal pentraxin 1 (NPTX1) has been implicated in Alzheimer's disease, being present and around dystrophic neurons plaques, affecting glutamatergic transmission postsynaptically mediating effects of amyloidβ. Here, we confirm the presence NPTX1 plaques postmortem disease brain report that acutely applied human increases paired-pulse ratio at mouse CA3-CA1 hippocampal synapses, indicating a decrease glutamate release. In contrast, chronic exposure to NPTX1, NPTX2, or NPTX receptor decreases...
Abstract Human astrocytomas and oligodendrogliomas are defined by mutations of the metabolic enzymes isocitrate dehydrogenase (IDH) 1 or 2, resulting in production abnormal metabolite D-2 hydroxyglutarate. Here, we studied effect mutant IDH on cell proliferation apoptosis a glioma mouse model. Tumors were generated inactivating Pten p53 forebrain progenitors compared with tumors additionally expressing Idh1 R132H mutation. Idh-mutant cells proliferated less vitro mice survived significantly...
Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance human pathogenesis, most do not recapitulate the histogenesis of disease. Recently, a large series gliomas and medulloblastomas were analyzed for signatures prognosis therapeutic response. Using mouse model system generates three distinct types intrinsic brain tumors, we correlated RNA protein expression levels with tumors. A...
To identify biomarkers for glioma growth, invasion and progression, we used a candidate gene approach in mouse models with two complementary brain tumour phenotypes, developing either slow-growing, diffusely infiltrating gliomas or highly proliferative, non-invasive primitive neural tumours. In microRNA screen first identified microRNA-449a as most significantly differentially expressed between these types. miR-449a has target dependent effect, inhibiting cell growth migration by...
Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated development and disease. In brain, targeted has become a mainstream approach to study neurodegeneration tumourigenesis. The use Cre-loxP system tumourigenesis adult CNS can be limited, when promoter (such as GFAP) also transiently expressed during development, which result progenies different lineages. Engineering transgenic mice expressing Cre recombinase fused mutant human...
Vascular compromise occurs early in Alzheimer’s disease (AD) and other dementias 1–3 . Amyloid β (Aβ) reduces cerebral blood flow 4–6 and, as most of the vasculature resistance is capillaries 7 , Aβ might mainly act on contractile pericytes capillary walls 8–10 Employing human tissue to establish disease-relevance, rodent experiments define mechanism, we now show that constricts brain at pericyte locations subjects with cognitive decline. Applying soluble 1-42 oligomers live cortical...
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<p>PDF file, 929K, Derivation and testing of a human sPNET-specific gene signature.</p>
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<p>PDF file, 1557K, Expression patterns of tumours generated in a p53/PTEN/Rb background.</p>
<p>PDF file, 1105K, Derivation and testing of a human oligodendroglial gene signature.</p>
<p>PDF file, 736K, Derivation of a human ATRT-specific gene set.</p>
<p>PDF file, 1743K, p53 sequencing of Rb/Pten tumours and in vitro recombined neurospheres.</p>