A5056840086- Asthma and respiratory diseases
- Neonatal Respiratory Health Research
- IL-33, ST2, and ILC Pathways
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Kruppel-like factors research
- T-cell and B-cell Immunology
- Chronic Myeloid Leukemia Treatments
- T-cell and Retrovirus Studies
- Pediatric health and respiratory diseases
- Genomics and Chromatin Dynamics
- Allergic Rhinitis and Sensitization
- Systemic Sclerosis and Related Diseases
- Dermatology and Skin Diseases
- NF-κB Signaling Pathways
- Inflammatory Bowel Disease
- Eosinophilic Esophagitis
- Helicobacter pylori-related gastroenterology studies
- Hops Chemistry and Applications
- Microscopic Colitis
- Mycobacterium research and diagnosis
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Osteoarthritis Treatment and Mechanisms
- Immunotherapy and Immune Responses
- Pulmonary Hypertension Research and Treatments
Helmholtz Zentrum München
2023-2024
Genomics (United Kingdom)
2024
Manchester Academic Health Science Centre
2011-2023
University of Manchester
2011-2023
Manchester University NHS Foundation Trust
2008-2023
Salford Royal NHS Foundation Trust
2019-2020
National Health Service
2008
BackgroundFilaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy. Household consumption is allergy, and allergen in household dust correlates consumption.ObjectiveWe sought determine whether environmental exposure increases the odds of allergy FLG modulate these odds.MethodsExposure antigen within first year life was measured a population-based birth cohort. Peanut sensitization (defined by using oral food challenges or component-resolved...
Few genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel variants associated with asthma, see whether previously identified for all types of contribute and provide mechanistic insights using expression analyses in patients asthma.In this genome-wide association study, we used a two-stage case-control design. In stage 1, genotyped patient-level data from two UK cohorts (the Genetics Asthma Severity Phenotypes [GASP] initiative the Unbiased BIOmarkers...
Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening physical barrier FLG-deficient individuals may potentiate effect environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with exposures (pets and dust mites) relation to development eczema.We used data obtained early life a high-risk birth cohort Denmark replicated findings unselected United Kingdom....
Osteoarthritis is a complex disease with huge public health burden. Genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated sequence variants, but the effector genes underpinning these signals remain largely elusive. Understanding chromosome organisation in three-dimensional (3D) space essential for identifying long-range contacts between distant genomic features (e.g., and regulatory elements), tissue-specific manner. Here, we generate first whole genome...
Chromatin looping between regulatory elements and gene promoters presents a potential mechanism whereby disease risk variants affect their target genes. In this study, we use H3K27ac HiChIP, method for assaying the active chromatin interactome in two cell lines: keratinocytes skin lymphoma-derived CD8+ T cells. We integrate public datasets lymphoblastoid line primary CD4+ cells identify targets at loci skin-related disorders. Interacting genes enrich pathways of known importance each trait,...
Given the role of vascular endothelial growth factor (VEGF) in lung development, we hypothesized that polymorphisms VEGF-A may be associated with function.The current study was designed to assess genetic variants as determinants airway function from infancy through early adulthood.Association between five single-nucleotide (SNPs) and were assessed longitudinally two unselected birth cohorts cross-sectionally among infants. Replication SNPs conducted adults children asthma. We investigated...
The IL1RL1 (ST2) gene locus is robustly associated with asthma; however, the contribution of single nucleotide polymorphisms (SNPs) in this to specific asthma subtypes and functional mechanisms underlying these associations remain be defined. We tested for association between region SNPs characteristics as defined by clinical immunological measures addressed effects genetic variants lung tissue airway epithelium. Utilizing 4 independent cohorts (Lifelines, Dutch Asthma GWAS [DAG], Genetics...
Abstract Background We investigated the association between genetic variation in chromosomal region 20p13‐p12 ( ADAM 33 and flanking genes ATRN , GFRA 4 SIGLEC 1 HSPA 12 B ) asthma. Amongst asthmatics, we then variants asthma severity. evaluated effect of environmental tobacco smoke ETS exposure context variants. Methods In a case–control study, recruited 423 asthmatic children 414 non‐asthmatic controls (age 5–18 yr). measured lung function extracted data on hospitalisation for exacerbation...
Abstract Background Genome-wide association studies (GWAS) have uncovered many genetic risk loci for psoriasis, yet remain uncharacterised in terms of the causal gene and their biological mechanism disease. This is largely a result findings that over 90% GWAS variants map outside protein-coding DNA instead are enriched cell type- stimulation-specific regulatory regions. Results Here, we use disease-focused Capture Hi-C (CHi-C) experiment to link psoriasis-associated with target genes...
We investigated the interaction between genetic variants in endotoxin signalling pathway and domestic exposure relation to asthma presence, amongst children with asthma, we explored association of these hospital admissions due exacerbations.In a case-control study, analysed data from 824 (417 asthmatics, 407 controls; age 5-18 yr). Amongst extracted on hospitalization for exacerbation medical records. Endotoxin was measured dust samples collected homes. included 26 single-nucleotide...
Abstract Background Genetic susceptibility to colonic inflammation is poorly defined at the gene level. Although Genome Wide Association studies (GWAS) have identified loci in human genome which confer Inflammatory Bowel Disease (Crohn’s and Ulcerative Colitis), it not clear if precise exist specific locations within gut e.g. small versus large intestine. Susceptibility for colitis particular been mouse, although candidate genes date. We previously shown that infection with Trichuris muris (...
Systemic sclerosis (SSc) is a complex autoimmune disease with strong genetic component. However, most of the genes associated are still unknown because variants affect mostly noncoding intergenic elements genome. We used functional genomics to translate findings into better understanding disease.
Abstract Background Maternal smoking increases the risk of respiratory symptoms in children. Glutathione S ‐transferases ( GST s) detoxify xenobiotics from tobacco smoke, and functional polymorphism gene(s) could predispose children to detrimental effects maternal smoking. Our objective was investigate interactions between variants relation development wheezing during childhood whether any such interaction changes with time. Methods In a population‐based birth cohort, we assessed current...
Immune-specific genes as well responsible for the formation and integrity of epidermal barrier have been implicated in pathogeneses allergic sensitization. This study sought to determine whether an epistatic effect (gene-gene interaction) between genetic variants within interleukin 4 receptor (IL4R) filaggrin (FLG) predispose development Data from two birth cohort studies were analyzed, namely Isle Wight (IOW; n = 1,456) Manchester Asthma Allergy Study (MAAS; 1,058). In IOW study, one...
Abstract The lung is a dynamic mucosal surface constantly exposed to variety of immunological challenges including harmless environmental antigens, pollutants, and potentially invasive microorganisms. Dysregulation the immune system at this crucial site associated with range chronic inflammatory conditions asthma Chronic Pulmonary Obstructive Disease (COPD). However, due its relative inaccessibility, our fundamental understanding human compartment limited. To address this, we performed flow...
Functional enrichment analysis of genome-wide association study (GWAS)-summary statistics has suggested that CD4+ T-cells play an important role in asthma pathogenesis. Despite this, are under-represented transcriptome studies. To fill the gap, 3'-RNA-Seq was used to generate gene expression data on (isolated within 2 h from collection) peripheral blood participants with well-controlled (n = 32) and healthy controls 11). Weighted Gene Co-expression Network Analysis (WGCNA) identify sets...
Abstract Background/Aims Osteoarthritis is a complex disease with huge public health burden. Genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated sequence variants, but the effector genes underpinning these signals remain largely elusive. Understanding chromosome organisation in 3D space essential for identifying long-range contacts between distant genomic features (e.g., and regulatory elements), tissue-specific manner. Here, we generate first whole...