A5103069228- T-cell and B-cell Immunology
- Rheumatoid Arthritis Research and Therapies
- Autoimmune and Inflammatory Disorders Research
- Cytokine Signaling Pathways and Interactions
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Genomics and Chromatin Dynamics
- Heart Rate Variability and Autonomic Control
- NF-κB Signaling Pathways
- Adolescent and Pediatric Healthcare
- Genetic Associations and Epidemiology
- IL-33, ST2, and ILC Pathways
- Nutrition, Genetics, and Disease
- Dermatology and Skin Diseases
- Cardiac electrophysiology and arrhythmias
- Acute Lymphoblastic Leukemia research
- Kruppel-like factors research
- Celiac Disease Research and Management
- Genomics and Rare Diseases
- Psoriasis: Treatment and Pathogenesis
- T-cell and Retrovirus Studies
University of Manchester
2015-2025
Versus Arthritis
2010-2025
Genomics (United Kingdom)
2015-2023
Henry Royce Institute
2023
Manchester Academic Health Science Centre
2010-2020
Institute of Immunology
2020
MRC Epidemiology Unit
2009-2019
Babraham Institute
2015
Pfizer (United States)
2013
Eli Lilly (United States)
2013
Abstract Genome-wide association studies have been tremendously successful in identifying genetic variants associated with complex diseases. The majority of signals are intergenic and evidence is accumulating that a high proportion lie enhancer regions. We use Capture Hi-C to investigate, for the first time, interactions between four autoimmune diseases their functional targets B- T-cell lines. Here we report numerous looping provide only minority common both lines, suggesting may be highly...
Abstract Human natural killer (NK) cells in peripheral blood perform many functions, and classification of specific subsets has been a longstanding goal. We report single-cell RNA sequencing NK cells, comparing gene expression unstimulated interleukin (IL)-2–activated from healthy cytomegalovirus (CMV)-negative donors. Three cell resembled well-described populations; CD56brightCD16−, CD56dimCD16+CD57−, CD56dimCD16+CD57+. CD56dimCD16+CD57− subdivided to include population with higher...
Abstract Early passage mouse embryo fibroblasts, 3T3 cell lines, and early diploid human fibroblasts grew to higher densities in tissue culture medium supplemented with serum than defibrinogenated platelet‐poor plasma (PPP). Unlike the cells, displayed this differential growth response only presence of hypophysiologic concentrations calcium. The addition heat‐treated extracts platelets PPP‐supplemented stimulated replication both normal cells fibroblasts. Human or transformed by either...
The composition of the skin microbiome is predicted to play a role in development conditions such as atopic eczema and psoriasis. 16S rRNA gene sequencing allows investigation bacterial microbiota. A significant challenge this field cost effective high throughput methodologies for robust interrogation microbiota, where biomass low. Here we describe validation (ribosomal ribonucleic acid) from microbiome, using Illumina MiSeq platform, selection primer amplify regions compare results with...
The identification of causal genes from genome-wide association studies (GWAS) is the next important step for translation genetic findings into biologically meaningful mechanisms disease and potential therapeutic targets. Using novel chromatin interaction detection techniques allele specific assays in T B cell lines, we provide compelling evidence that redefines at 6q23 locus, one most loci confers autoimmunity risk.Although function disease-associated non-coding single nucleotide...
Study Objective: To determine the efficacy of allogeneic bone marrow transplantation for severe myelodysplasia, and to identify variables predictive outcome. Design: Case series study. Setting: A referral-based transplant center. Patients: Consecutive 59 patients with myelodysplasia or closely related disorders either life-threatening cytopenia a progressive increase in blast percentage. Intervention: Patients were treated high-dose cyclophosphamide total body irradiation followed by from an...
Abstract Introduction Genome wide association studies, replicated by numerous well powered validation have revealed a large number of loci likely to play role in susceptibility many multifactorial diseases. It is now established that some these are shared between diseases with similar aetiology. For example, autoimmune been associated variants the PTPN22, TNFAIP3 and CTLA4 genes. Here we attempted define overlapping genetic rheumatoid arthritis (RA), type 1 diabetes (T1D) coeliac disease...
The most consistent finding derived from the WTCCC GWAS for rheumatoid arthritis (RA) was association to a SNP at 6q23. We performed fine-mapping of region in order search 6q23 additional disease variants. 3962 RA patients and 3531 healthy controls were included study. found 18 SNPs associated with RA. showing strongest rs6920220 [P = 2.6 × 10−6, OR (95% CI) 1.22 (1.13–1.33)]. next strongly rs13207033 0.0001, 0.86 (0.8–0.93)] which perfectly correlated rs10499194, previously US/European...
Abstract Objective To define interactions between the HLA–DRB1 shared epitope (SE), PTPN22 , and smoking in cyclic citrullinated peptide (CCP) antibody– rheumatoid factor (RF)–positive –negative arthritis (RA). Methods Data on ∼5,000 RA patients ∼3,700 healthy controls recruited from 6 centers UK were analyzed; not all had both genotype data available for study. The magnitude of association was assessed autoantibody‐positive ‐negative subgroups. effect antibody status among cases following...
In canine, isovolumetric, left ventricle preparations, stimulation of the cardiac end a cut cervical vagus nerve evokes biphasic change ventricular systolic pressure (LVSP). Characteristically, there is definite reduction LVSP during stimulus, followed by slight increase after cessation stimulation. The magnitude vagal considerably augmented when sympathetic activity increased either directly (by electrical stellate ganglion) or reflexly lowering carotid sinus pressure). These results...
Genome-wide association studies have identified genetic variation contributing to complex disease risk. However, assigning causal genes and mechanisms has been more challenging because disease-associated variants are often found in distal regulatory regions with cell-type specific behaviours. Here, we collect ATAC-seq, Hi-C, Capture Hi-C nuclear RNA-seq data stimulated CD4+ T cells over 24 h, identify functional enhancers regulating gene expression. We characterise changes DNA interaction...
Abstract Background Genome-wide association studies have reported more than 100 risk loci for rheumatoid arthritis (RA). These are shown to be enriched in immune cell-specific enhancers, but the analysis so far has excluded stromal cells, such as synovial fibroblasts (FLS), despite their crucial involvement pathogenesis of RA. Here we integrate DNA architecture, 3D chromatin interactions, accessibility, and gene expression FLS, B T cells with genetic fine mapping RA loci. Results We identify...
The concept of susceptibility genes common to different autoimmune diseases is now firmly established with previous studies demonstrating overlap loci conferring type 1 diabetes (T1D) both Coeliac disease and multiple sclerosis. Rheumatoid arthritis (RA) an archetypal we, therefore, targeted putative T1D for genotyping in UK RA cases unrelated controls. A novel locus at AFF3 was identified convincing evidence association a combined sample cohort 6819 12 650 controls [OR 1.12 95% confidence...
Juvenile idiopathic arthritis (JIA) is an umbrella term for all chronic childhood arthropathies and can be divided into seven subtypes. It includes the enthesitis related (ERA) subtype which displays symptoms similar to ankylosing spondylitis (AS) juvenile-onset psoriatic has similarities (PsA) psoriasis (Ps). We, therefore, hypothesized that two well-established susceptibility loci AS Ps, ERAP1 IL23R, could also confer these JIA Single nucleotide polymorphisms (SNPs) in (rs30187) IL23R...
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,...