A5085653682- Neuroinflammation and Neurodegeneration Mechanisms
- Malaria Research and Control
- Acute Ischemic Stroke Management
- Single-cell and spatial transcriptomics
- Mosquito-borne diseases and control
- Sepsis Diagnosis and Treatment
- Immune Cell Function and Interaction
- Barrier Structure and Function Studies
- Immune cells in cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Bacillus and Francisella bacterial research
- Neurofibromatosis and Schwannoma Cases
- Meningioma and schwannoma management
- Complement system in diseases
- Adipose Tissue and Metabolism
- Ear and Head Tumors
- Immune responses and vaccinations
- Intracerebral and Subarachnoid Hemorrhage Research
- Trypanosoma species research and implications
- Inflammasome and immune disorders
- Cytomegalovirus and herpesvirus research
- Long-Term Effects of COVID-19
- COVID-19 Clinical Research Studies
- Drug Transport and Resistance Mechanisms
- Extracellular vesicles in disease
University of Manchester
2016-2025
Manchester Academic Health Science Centre
2017-2025
AbbVie (United States)
2025
Institute of Immunology
2024
Centre for Inflammation Research
2023
Roslin Institute
2023
Queen Mary University of London
2023
Weatherford College
2023
University of Glasgow
2023
National Institute of Biomedical Research
2023
Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that prone to intracranial bleeding. We aimed determine whether presence can identify patients at high risk symptomatic haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient attack.
Blood–brain barrier breakdown worsens ischaemic damage, but it is unclear how molecules breach the blood–brain in vivo. Using obese ob/ob mouse as a model of enhanced breakdown, we investigated stroke-induced structural changes to microvasculature related permeability. Ob/ob mice underwent middle cerebral artery occlusion, followed by 4 or 24 h reperfusion. integrity was assessed using IgG and horseradish peroxidase staining, structure two-dimensional three-dimensional electron microscopy....
The development of effective therapies for stroke continues to face repeated translational failures. Brain endothelial cells form paracellular and transcellular barriers many blood-borne therapies, the efficient delivery strategies is highly warranted. Here, in a mouse model stroke, we show selective recruitment clinically used liposomes into ischemic brain that correlates with biphasic blood barrier (BBB) breakdown. Intravenous administration mice exposed transient middle cerebral artery...
Myeloid cells are highly prevalent in glioblastoma (GBM), existing a spectrum of phenotypic and activation states. We now have limited knowledge the tumor microenvironment (TME) determinants that influence localization functions diverse myeloid cell populations GBM. Here, we utilized orthogonal imaging mass cytometry with single-cell spatial transcriptomic approaches to identify map various human GBM (TME). Our results show different distinct reproducible compartmentalization patterns TME is...
Although circulatory shock related to lethal toxin (LeTx) may play a primary role in lethality due Bacillus anthracis infection, its mechanisms are unclear. We investigated whether LeTx-induced is associated with inflammatory cytokine and nitric oxide (NO) release. Sprague-Dawley rats central venous arterial catheters received 24-h infusions of LeTx (lethal factor 100 microg/kg; protective antigen 200 microg/kg) that produced death beginning at 9 h 7-day mortality rate 53%. By h, mean blood...
The murine model of experimental cerebral malaria (ECM) has been utilised extensively in recent years to study the pathogenesis human (HCM). However, it proposed that aetiologies ECM and HCM are distinct, and, consequently, no useful mechanistic insights into can be obtained from studying model. Therefore, order determine similarities differences pathology HCM, we have performed first spatial quantitative histopathological assessment syndrome. We demonstrate accumulation parasitised red...
Obesity increases the risk for ischaemic stroke and is associated with worse outcome clinically experimentally. Most experimental studies have used genetic models of obesity. Here, a more relevant model, diet-induced obesity, was to study impact obesity over time on inflammatory response after stroke.Male C57BL/6 mice were maintained high-fat (60% fat) or control (12% diet 2, 3, 4 6 months when induced by transient occlusion middle cerebral artery (MCAo) either 20 (6-month diet) 30 min (2-,...
Intravenous immunoglobulin (IVIG) with high titers to West Nile virus was used as an adjuvant therapy for a patient encephalitis that did not respond supportive care. We present this case report and review the evidence supporting use of high-titer IVIG.
Significance Cerebral malaria (CM) is a neurological complication of infection that, despite antimalarial drug treatment, results in fatality or neurodisability approximately 25% cases. Thus, there an urgent clinical need to develop therapies that can improve the efficacy drugs prevent reverse cerebral pathology. Here, we show experimental mouse model CM (ECM) IL33 administration survival and reduce pathology brain over alone. Mechanistically, demonstrate enhances recovery from ECM by...
Background and Purpose- A major process contributing to cell death in the ischemic brain is inflammation. Inflammasomes are multimolecular protein complexes that drive inflammation through activation of proinflammatory cytokines, such as IL (interleukin)-1β. Preclinical evidence suggests IL-1β contributes a worsening injury. Methods- Using mouse middle cerebral artery thrombosis model, we examined inflammatory response after stroke contribution NLRP3 (NACHT, LRR PYD domains-containing 3)...
Abstract Bilateral vestibular schwannoma is the hallmark of NF2-related schwannomatosis, a rare tumour predisposition syndrome associated with lifetime surgical interventions, radiotherapy and off-label use anti-angiogenic drug bevacizumab. Unilateral develops sporadically in non-NF2-related schwannomatosis patients for which there are no treatment options available. Tumour-infiltrating immune cells such as macrophages T-cells correlate increased growth, suggested to be similar sporadic...
CD8+ T cells have been shown to play a critical role in the pathogenesis of experimental cerebral malaria (ECM) mice, but their development human (HCM) remains unclear. Thus, this study we provided first direct contrast accumulation brain during HCM and ECM. cases were from children who died Plasmodium falciparum at Queen Elizabeth Central Hospital (Malawi) between 2003 2010. ECM was induced by infecting C57BL/6J mice with P. berghei ANKA. We demonstrate similarities intracerebral cell...
In animal models, treatment with 5H3, a fully human protective antigen-directed monoclonal antibody (PA-MAb), improved survival when administered close to the time of Bacillus anthracis lethal toxin (LeTx) bolus or live bacterial challenge. However, PA-MAb would be most valuable clinically if it were beneficial even after onset shock and lethality due LeTx.We investigated effects versus placebo in rats (n=324) at 3, 6, 9, 12 h initiation 24-h LeTx infusion.In receiving placebo, mean arterial...
Abstract During recovery, stroke patients are at risk of developing long-term complications that impact quality life, including changes in body weight and composition, depression anxiety, as well an increased subsequent vascular events. The aetiologies time-course these post-stroke have not been extensively studied poorly understood. Therefore, we assessed metabolic markers behaviour after middle cerebral artery occlusion mice. These outcomes were also the context obesity, a common...
Background Stroke is a major cause of disability and mortality. Poorer outcome after stroke associated with concomitant inflammatory infectious disease. Periodontitis chronic disease the dental supporting structures prominent risk factor for many systemic disorders, including cardiovascular stroke. While epidemiological studies suggest that periodontitis increases likelihood stroke, its impact on severity poorly understood. Here, we sought to determine contribution acute pathology. Methods...
Open-angle glaucoma (OAG) is a chronic and degenerative disorder that causes optic nerve damage potential blindness. The objective of this review to provide brief overview on OAG, with emphasis the importance β-blockers α2-agonists for eye care. Timolol maleate (1) brimonidine tartrate (2) are an important β-blocker α2-agonist, respectively. Both used in several medications treatment open-angle glaucoma. A literature various synthetic approaches timolol (1), drug substances presented. In...
Abstract NF2 -related Schwannomatosis ( SWN) is a rare disease characterised by the growth of multiple nervous system neoplasms, including bilateral vestibular schwannoma (VS). VS tumours are extensive leucocyte infiltration. However, immunological landscape in and spatial determinants within tumour microenvironment that shape trajectory presently unknown. In this study, to elucidate complex networks across VS, we performed imaging mass cytometry (IMC) on clinically annotated samples from...
Abstract Liver fibrosis is a major cause of death worldwide. As progressive step in chronic liver disease, almost always diagnosed too late with limited treatment options. Here, we uncover the spatial transcriptional landscape driving human using single nuclei RNA and Assay for Transposase-Accessible Chromatin (ATAC) sequencing to deconvolute multi-cell transcriptomic profiling cirrhosis. Through multi-modal data integration, define molecular signatures cell state transitions disease an...
Chronic consumption of diets high in fat leads to obesity and can negatively affect brain function. Rodents made obese by long-term maintenance on a high-fat diet have worse outcome after experimental stroke. High-fat for only three days does not induce but has rapid effects the including memory impairment. However, effect brief periods feeding or absence stroke is unknown. We therefore tested an acute period (three days) C57B/6 mice middle cerebral artery occlusion (MCAo). In contrast...
Inflammation is an established contributor to disease and the NLRP3 inflammasome emerging as a potential therapeutic target. A number of small molecule inhibitors pathway have been described. Here we analysed most promising these inhibitor classes side by assess relative potency selectivity for their respective putative targets. Assessed using ASC inflammasome-speck formation, release IL-1β, in both human monocyte/macrophage THP1 cells primary mouse microglia, compared P2X7 inhibitors,...
Haemorrhagic stroke represents a significant public health burden, yet our knowledge and ability to treat this type of are lacking. Previously we showed that can target ischaemic-stroke lesions by selective translocation lipid nanoparticles through the site blood-brain barrier (BBB) disruption. The data presented in study provide compelling evidence haemorrhagic mice induces BBB injury mimics key features human pathology and, more importantly, provides gate for entry nanoparticles-based...