A5108005055- COVID-19 Clinical Research Studies
- Long-Term Effects of COVID-19
- SARS-CoV-2 and COVID-19 Research
- Asthma and respiratory diseases
- Respiratory Support and Mechanisms
- Carcinogens and Genotoxicity Assessment
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Allergic Rhinitis and Sensitization
- Phagocytosis and Immune Regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Animal testing and alternatives
- Renal and related cancers
- Neonatal Respiratory Health Research
- Nutrition and Health in Aging
- Proteoglycans and glycosaminoglycans research
- Frailty in Older Adults
- Health, Environment, Cognitive Aging
- Aortic aneurysm repair treatments
- Caveolin-1 and cellular processes
- Synthesis and biological activity
- Dermatological diseases and infestations
- Immune cells in cancer
- Blood disorders and treatments
- Mycotoxins in Agriculture and Food
- Chemokine receptors and signaling
University of Manchester
2018-2024
Manchester Academic Health Science Centre
2020-2023
Institute of Immunology
2020-2021
Centre for Inflammation Research
2018-2019
Gentronix (United Kingdom)
2009-2010
Queen's University
2004
University of Leicester
1995
St George's, University of London
1992
COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal profiling on both whole blood peripheral mononuclear cells (PBMCs) of hospitalized patients during peak pandemic in UK. Here, we report key signatures present shortly after hospital admission that were severity COVID-19. Immune related to shifts neutrophil T...
BackgroundEmerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these presently remains ill-defined.MethodsHere, we describe phenotypic functional characteristics of B T cells hospitalized COVID-19 during acute at 3–6 months convalescence.FindingsWe report alterations cell subsets observed were largely recovered convalescent patients. In...
Summary Background The Th2 immune response in the nasal mucosa of subjects with allergic rhinitis is mediated by allergen‐specific IgE. Moreover, these show positive responses for markers systemic atopy, including skin sensitivity and raised serum IgE titres. In contrast, idiopathic (IR) similar histological mucosal features differ being defined as non‐allergic because they have negative atopic responses. Objective We hypothesized that it possible to an disease pathway localized...
Little is known about the impact of viral infections on lung matrix despite its important contribution to mechanical stability and structural support. The composition also indirectly controls inflammation by influencing cell adhesion, migration, survival, proliferation differentiation. Hyaluronan a significant component extracellular production degradation must be carefully balanced. We have discovered an imbalance in hyaluronan following resolution severe influenza virus infection, driven...
Background COVID-19 is associated with a dysregulated immune response but it unclear how dysfunction contributes to the chronic morbidity persisting in many patients during convalescence (long COVID). Methods We assessed phenotypical and functional changes of monocytes hospitalisation up 9 months following COVID-19, respiratory syncytial virus or influenza A. Patients progressive fibrosing interstitial lung disease were included as positive control for severe, ongoing injury. Results...
Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present different disease severity. Here, we determined 171 microRNAomes from 58 hospitalized (Cohort 1) of 25 in the same samples. Combining microRNA (miRNA) measurements allowed for discrimination severe cases greater accuracy than using miRNA or alone. Severity group-specific associations between miRNAs COVID-19-associated (e.g., IL6, CCL20) clinical hallmarks...
Genotoxicity can be assessed by monitoring expression of a GADD45a–GFP reporter in the human lymphoblastoid cell line TK6. A flow cytometric method has been developed to effectively distinguish GFP fluorescence from coloured and fluorescent test samples as well S9 liver extracts used generate metabolites pro-genotoxins. The includes use propidium iodide exclusion for determination cellular viability. This paper describes development, derivation decision thresholds identification genotoxins...
AIM: To determine the role of intercellular adhesion molecule-1 (ICAM-1) in immune mediated damage glomerulonephritis, and whether its expression correlates with disease activity. METHODS: Fifty three renal biopsy specimens from a range non-immune low grade high glomerulonephritides were stained ICAM-1. Positivity was assessed tubules. Tubular accompanying interstitial inflammation also noted. The ICAM-1 positivity damaged undamaged tubules correlated groups disease. RESULTS: observed this...
Epithelial cell proliferation, division, and differentiation are critical for barrier repair following inflammation, but the initial trigger this process is unknown. Here we define that sensing of apoptotic cells by TAM receptor tyrosine kinase Axl a indicator tracheal basal expansion, cycle reentry, symmetrical division. Furthermore, once pool has expanded, silencing required their differentiation. Genetic depletion triggers asymmetrical leading to epithelial ciliated regeneration. This...
Abstract Background The pathogenesis of COVID-19, caused by a novel strain coronavirus (SARS-CoV-2), involves complex host-virus interaction and is characterised an exaggerated immune response, the specific components which are poorly understood. Here we report outcome longitudinal profiling study in hospitalised patients during peak COVID-19 pandemic UK show relationship between responses severity clinical presentation. Methods Coronavirus Immune Response Clinical Outcomes (CIRCO) was...
Abstract The glucose-6-phosphatase catalytic subunit 3 (G6PC3) encodes a ubiquitously expressed enzyme that regulates cytoplasmic glucose availability. Loss-of-function biallelic G6PC3 mutations cause severe congenital neutropenia and diverse spectrum of extra-hematological manifestations, among which inflammatory bowel disease (IBD) has been anecdotally reported. Neutrophil function clinical response to granulocyte colony-stimulating factor (G-CSF) hematopoietic stem cell transplantation...
The pulmonary extracellular matrix (ECM) is a complex network of proteins which primarily defines tissue architecture and regulates various biochemical biophysical processes. It dynamic system comprising two main structures (the interstitial the basement membrane) undergo continuous, yet highly regulated, remodelling. This remodelling process essential for homeostasis uncontrolled regulation can lead to pathological states including chronic obstructive disease (COPD). Altered expression ECM...
The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types extracellular matrix components. role of immune cells in environment is crucial for dampening inflammation maintaining homeostasis. Macrophages are innate that influenced by their tissue microenvironment. However, the multifunctional macrophages remains unclear. Flow imaging cytometry were used to determine relative expression CD81 CX3CR1 (C-X3-C motif chemokine receptor 1) macrophages....
Emerging studies indicate that some COVID-19 patients suffer from persistent symptoms including breathlessness and chronic fatigue; however the long-term immune response in these presently remains ill-defined. Here we describe phenotypic functional characteristics of B T cells healthy individuals with acute or convalescent COVID-19. We report alterations cell subsets observed were largely recovered patients. In contrast, displayed persistence a cytotoxic programme evident CD8+ as well...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the clinical COVID-19 is associated with an exaggerated immune response and monocyte infiltrates lungs other peripheral tissues. It now increasingly recognised that chronic morbidity persists some patients. We recently demonstrated profound alterations of monocytes hospitalised currently unclear whether these abnormalities resolve or progress following patient discharge. show here blood convalescent...
Abstract Identification of pathways preventing recovery from acute respiratory viral infection is under-studied but essential for long-term health. Using unbiased proteomics, we reveal an unexpected persistent reduction in lung basement membrane proteins mice recovered influenza infection. Basement provides a critical scaffold heterogeneous cell types and the they secrete/express at endothelial epithelial barrier. Further peptide location fingerprinting analysis shows inherent...
Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present different disease severity. Here, we determined 171 microRNAomes from 58 hospitalised (Cohort 1) of 25 in the same samples. Combining microRNA (miRNA) measurements allowed for discrimination severe cases greater accuracy than using miRNA or alone. Severity group-specific associations between miRNAs COVID-19-associated (e.g. IL6, CCL20) clinical hallmarks neutrophilia,...
Exposure to tobacco smoke (TS) for 4 days induces a reproducible steroid-insensitive lung inflammation in the mouse. The effect of adding viral mimetic poly IC (PIC) TS-exposed mice was examined with aim defining translational aspects model human disease.