A5011330442- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pediatric health and respiratory diseases
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- IL-33, ST2, and ILC Pathways
- Protein Degradation and Inhibitors
- Respiratory Support and Mechanisms
- Immune Cell Function and Interaction
- Neonatal Respiratory Health Research
- Respiratory and Cough-Related Research
- Peptidase Inhibition and Analysis
- MicroRNA in disease regulation
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Genetics and Neurodevelopmental Disorders
- T-cell and B-cell Immunology
- Respiratory viral infections research
- Cardiac and Coronary Surgery Techniques
- Cancer-related gene regulation
- Parathyroid Disorders and Treatments
- Macrophage Migration Inhibitory Factor
- Glutathione Transferases and Polymorphisms
- Congenital Diaphragmatic Hernia Studies
- Cardiac Fibrosis and Remodeling
Imperial College London
2009-2020
Queen Mary University of London
2020
King's College London
2018
Lung Institute
2013-2017
Royal Brompton & Harefield NHS Foundation Trust
2015-2017
British Airways (United Kingdom)
2011-2015
National Institute for Health Research
2015
National Institutes of Health
2009-2014
Asthma UK
2009
Guy's Hospital
2009
In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses their role in driving pulmonary inflammation stable COPD is unknown.To investigate immunity pathways bronchial mucosa bronchoalveolar lavage (BAL) patients with different severity control healthy smokers non-smokers.Innate mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ...
Respiratory virus infections are commonly associated with COPD exacerbations, but little is known about the mechanisms linking infection to exacerbations. Pathogenic in stable include oxidative and nitrosative stress reduced activity of histone deacetylase-2 (HDAC2), their roles exacerbations unknown. We investigated (O&NS) HDAC2 using experimental rhinovirus infection.Nine subjects (Global Initiative for Chronic Obstructive Lung Disease stage II), 10 smokers, 11 nonsmokers were successfully...
Persistent hepatitis B virus infection is a major risk factor for hepatocellular carcinoma, the most frequent cancer in some developing countries. Up to 95% of those infected at birth and 15% after neonatal period fail clear virus, together resulting approximately 350 million persistent carriers worldwide. Via whole genome scan Gambian families, we have identified susceptibility locus as cluster class II cytokine receptor genes on chromosome 21q22. Coding changes two these genes, type I IFN...
About 5-10% of patients with asthma suffer from poorly-controlled disease despite corticosteroid (CS) therapy.We determined whether there were any differences in inflammatory biomarkers between severe and non-severe patients.Nineteen 20 recruited underwent collection induced sputum, bronchoalveolar lavage (BAL) fluid bronchial biopsies.Biopsy results showed no eosinophils (major basic protein positive), neutrophils, macrophages, T cells mast the submucosa. However, subbasement membrane (SBM)...
Airway smooth muscle (ASM) mass is increased in asthma, and ASM cells from patients with asthma are hyperproliferative release more IL-6 CXCL8. The BET (bromo- extra-terminal) family of proteins (Brd2, Brd3, Brd4) govern the assembly histone acetylation-dependent chromatin complexes. We have examined whether they modulate proliferation cytokine expression asthmatic by studying effect bromodomain mimics JQ1/SGCBD01 I-BET762. healthy individuals nonsevere severe asthmatics were pretreated...
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic disorders corticosteroid insensitivity. Its expression in the airways of patients obstructive pulmonary disease (COPD), a relatively steroid insensitive unclear, however. Sputum, bronchoalveolar lavage (BAL) macrophages serum were obtained from non-smokers, smokers COPD patients. To mimic oxidative stress-induced COPD, mice exposed to ozone for six-weeks treated ISO-1, MIF inhibitor,...
We investigated changes in gene expression that occur chronic obstructive pulmonary disease (COPD) after corticosteroid treatment and sought to identify the mechanisms regulate these changes. Biopsy samples were taken from patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage I II) before fluticasone propionate (FP)/salmeterol (SM) (50/500, 4 wk). Gene was measured by microarray confirmed real-time reverse transcription-quantitative PCR (RT-qPCR). The effect of FP...
We have generated a set of plasmids, based on the mobilizable shuttle vector pMIDG100, which can be used as tools for genetic manipulation Actinobacillus pleuropneumoniae and other members Pasteurellaceae. A tandem reporter plasmid, pMC-Tandem, carrying promoterless xylE gfpmut3 genes downstream multiple-cloning site (MCS), identification transcriptional regulators conditions favor gene expression from different cloned promoters. The ability to detect using system was validated in A. rpoE...
Chronic obstructive pulmonary disease (COPD) is associated with persistent inflammation and oxidative stress in susceptible individuals. Using microarray analysis of bronchial biopsy samples from patients COPD controls, we identified Wnt4 as being up-regulated COPD. Analysis showed a very strong correlation between IL8 gene expression, suggesting that plays role chronic lung inflammation. In vitro, induced proliferation human epithelial cells (BEAS-2B) normal primary concentration-dependent...
Progressive pulmonary fibrosis is the main cause of death in patients with systemic sclerosis (SSc) interstitial lung disease (ILD) and those idiopathic (IPF). Transforming growth factor-β (TGF-β) NADPH oxidase- (NOX-) derived reactive oxygen species (ROS) are drivers fibrosis. We aimed to determine role epigenetic readers, bromodomain extraterminal (BET) proteins regulation redox balance activated myofibroblasts.In TGF-β-stimulated fibroblasts, we investigated effect BET inhibitor JQ1 on...
In chronic obstructive pulmonary disease (COPD), oxidative stress regulates the inflammatory response of bronchial epithelium and monocytes/macrophages through kinase modulation has been linked to glucocorticoid unresponsiveness. Glycogen synthase-3β (GSK3β) inactivation plays a key role in mediating signaling processes upon reactive oxygen species (ROS) exposure. We hypothesized that GSK3β is involved stress-induced insensitivity COPD. studied levels phospho-GSK3β-Ser9, marker inactivation,...
Compared to females, males are more susceptible acute viral and other respiratory tract infections that display greater severity higher mortality. In contrast, females tend fare worse with chronic inflammatory diseases. Circulating 17β-estradiol (E2) is a female-specific factor may influence the progression of human lung Here we hypothesize E2 modulates response monocytes through microRNA (miRNA)-based modulation secretory leucoprotease inhibitor (SLPI), an antiprotease immunomodulatory...