A5017226715- Spondyloarthritis Studies and Treatments
- Cardiomyopathy and Myosin Studies
- Rheumatoid Arthritis Research and Therapies
- Cytokine Signaling Pathways and Interactions
- Psoriasis: Treatment and Pathogenesis
- Autoimmune and Inflammatory Disorders Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- interferon and immune responses
- Immune Cell Function and Interaction
- Cellular Mechanics and Interactions
- Immunodeficiency and Autoimmune Disorders
- Force Microscopy Techniques and Applications
- Fibromyalgia and Chronic Fatigue Syndrome Research
- NF-κB Signaling Pathways
- Inflammasome and immune disorders
- Muscle Physiology and Disorders
- Signaling Pathways in Disease
- Tendon Structure and Treatment
- T-cell and B-cell Immunology
- Immune cells in cancer
- Inflammatory mediators and NSAID effects
- Heat shock proteins research
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Systemic Lupus Erythematosus Research
University of Oxford
2008-2024
Centre Hospitalier Intercommunal de Poissy
2023-2024
MRC Weatherall Institute of Molecular Medicine
2023-2024
Centre for Human Genetics
2022-2023
Nuffield Orthopaedic Centre
2015-2023
John Radcliffe Hospital
2023
National Institute for Health Research
2015-2022
NIHR Oxford Musculoskeletal Biomedical Research Centre
2012-2020
National Health Service
2017
Oxford BioMedica (United Kingdom)
2016
The linear model of Th cell lineage commitment is being revised due to reports that mature cells can trans-differentiate into alternate lineages. This ability reprogram thought be regulated by epigenetic mechanisms control expression transcription factors characteristic opposing It unclear, however, what extent this new plasticity holds true in human subsets develop under physiological conditions vivo. We isolated vivo-differentiated Th1 and Th17 cells, as well intermediate Th1/17 identified...
Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present comprehensive transcriptomic epigenomic map disease-relevant blood immune cell subsets from AS patients healthy controls. We find that, while CD14
To explore the functional basis for association between ankylosing spondylitis (AS) and single-nucleotide polymorphisms (SNPs) in IL23R-IL12RB2 intergenic region. We performed conditional analysis on genetic data used epigenetic chromatin remodelling transcription factor (TF) binding to identify primary AS-associated SNP. Functional effects were tested luciferase reporter assays HEK293T cells allele-specific TF was investigated by electrophoretic mobility gel shift assays. IL23R IL12RB2 mRNA...
<h3>Objectives</h3> To identify the functional basis for genetic association of single nucleotide polymorphisms (SNP), upstream <i>RUNX3</i> promoter, with ankylosing spondylitis (AS). <h3>Methods</h3> We performed conditional analysis data and used ENCODE on chromatin remodelling transcription factor (TF) binding sites to primary AS-associated regulatory SNP in region. The effects this were tested luciferase reporter assays. Its TF investigated by electrophoretic mobility gel shift assays...
Abstract The molecular and cellular basis of health in human tendons remains poorly understood. Among tendons, hamstring tendon has markedly low pathology can provide a prototypic healthy reference. aim this study was to determine the transcriptomes location all cell types tendon. Using single nucleus RNA sequencing, we profiled 10 533 nuclei from four donors identified 12 distinct types. We confirmed presence two fibroblast types, endothelial cells, mural immune previously unreported...
The long terminal repeat (LTR) sequences of endogenous retroviruses and retroelements contain promoter elements are known to form chimeric transcripts with nearby cellular genes. Here we show that an LTR the THE1D retroelement family has been domesticated as alternative human IL2RB, gene encoding β subunit IL-2 receptor. confers expression specifically in placental trophoblast opposed its native transcription hematopoietic system. Rather than sequence-specific determinants, DNA methylation...
A new structural model is advanced to account for the specialized "catch" contraction of molluscan smooth muscles. The myosin thick filaments these muscles pictured as comprising a single layer molecules whose assembly and activity are controlled by underlying core paramyosin. This organization differs from that in other which grouped into bundles. catch state--in lifetime actin-myosin linkage extended--would depend directly on this special allows an interaction entire rod region with...
The relationship between membrane potential (Em) and the potassium equilibrium (EK) was investigated in hypoxic guinea pig papillary muscle. After more than 8 hours of hypoxia, cells with near normal Em (-86.2 +/- 0.9 mV) action potentials were observed. However, intracellular concentration ([K+]i) based on chemical analysis assumption that homogeneously distributed 41.8 4.3 mM; apparent EK -55.7 2.9 mV, significantly positive to Em. Measurements ion-selective microelectrodes revealed...
Abstract Tendon ruptures in humans have regularly been studied during the chronic phase of injury. However, early response to injury remains less investigated. Quadriceps tendons, which require prompt surgical treatment, offer a model investigate this response. Therefore, study aimed explore cellular changes ruptured compared healthy human quadriceps tendons. tendon samples were collected from patients undergoing tibial shaft fracture repair (healthy) or surgery for complete rupture...
Objectives To explore the functions of RUNX3 single nucleotide polymorphisms (SNPs) associated with ankylosing spondylitis (AS). Methods Individual SNP associations were evaluated in 4230 UK cases. Their effects on transcription factor (TF) binding, regulation, chromatin modifications, gene expression and interactions tested by database interrogation, luciferase reporter assays, electrophoretic mobility gel shifts, immunoprecipitation real-time PCR. Results We confirmed independent...
Objective To investigate the functional consequences of single‐nucleotide polymorphism rs4648889 in a putative enhancer upstream RUNX3 promoter associated with susceptibility to ankylosing spondylitis (AS). Methods Using nuclear extracts from Jurkat cells and primary human CD8+ T cells, effects on allele‐specific transcription factor (TF) binding were investigated by DNA pull‐down assay quantitative mass spectrometry (qMS), validation electrophoretic mobility shift (EMSA), Western blotting...
Background: Ankylosing Spondylitis (AS) is a common form of inflammatory spinal arthritis with complex aetiology and high heritability, involving more than 100 genetic associations. These include several AS-associated single nucleotide polymorphisms (SNPs) upstream RUNX3, which encodes the multifunctional RUNT-related transcription factor (TF) 3. The lead associated SNP rs6600247 (p = 2.6 × 10-15) lies ∼13kb RUNX3 promoter adjacent to c-MYC TF binding-site. effect genotype on DNA binding...
Dendritic cells (DCs) not only play a crucial role in activating immune but also suppressing them. We recently investigated SHIP's murine DCs terms of cell activation and found that TLR agonist-stimulated SHIP-/- GM-CSF-derived (GM-DCs) were far less capable than wild type (WT, SHIP+/+) GM-DCs at T proliferation. This was most likely because could up-regulate MHCII and/or co-stimulatory receptors following stimulation. However, the SHIP DC-induced suppression investigated.In this study we...
The IL23R region on chromosome 1 exhibits complex associations with ankylosing spondylitis (AS). We used publicly available epigenomic information and historical genetic association data to identify a putative regulatory element (PRE) in the intergenic between IL12RB2, which includes two single-nucleotide polymorphisms (SNPs) independently associated AS—rs924080 (P=2 × 10−3) rs11578380 10−4). In luciferase reporter assays, this PRE showed silencer activity (P<0.001). Haplotype conditional...
Background: This analysis assessed, on a group level, whether there is long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially placebo (PBO) who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was 78- week, randomized, controlled trial of PBO in MTX-naïve (<1 year) patients. Therapy adjusted at week 26: MTX-responders (R) achieved DAS28 (CRP) <3.2 weeks 22 and 26 (Period 1, P1) were re-randomized withdraw...