A5010755009- Rheumatoid Arthritis Research and Therapies
- Cancer-related molecular mechanisms research
- Cytokine Signaling Pathways and Interactions
- MicroRNA in disease regulation
- NF-κB Signaling Pathways
- Glycosylation and Glycoproteins Research
- Autoimmune and Inflammatory Disorders Research
- Chronic Lymphocytic Leukemia Research
- Mycobacterium research and diagnosis
- Inflammasome and immune disorders
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Chromatin Dynamics
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Endoplasmic Reticulum Stress and Disease
- Dermatological and Skeletal Disorders
- RNA Research and Splicing
- Pharmacological Effects of Natural Compounds
- Epigenetics and DNA Methylation
- Circular RNAs in diseases
- Peroxisome Proliferator-Activated Receptors
- CAR-T cell therapy research
- Biosimilars and Bioanalytical Methods
- interferon and immune responses
- Systemic Sclerosis and Related Diseases
University of Leeds
2012-2019
NIHR Leeds Musculoskeletal Biomedical Research Unit
2012-2019
Leeds Teaching Hospitals NHS Trust
2017-2018
St James's University Hospital
2012-2018
Wellcome Trust
2012-2018
Chapel Allerton Hospital
2015-2018
X-box binding protein 1 (XBP1) is a central regulator of the endoplasmic reticulum (ER) stress response. It induced via activation IRE1 sensor as part unfolded response (UPR) and has been implicated in several diseases processes. XBP1 can also be activated direct to Toll-like receptor (TLR) ligation independently UPR but pathogenic significance this mode not well understood. Here we show that TLR-dependent operative synovial fibroblasts (SF) patients with active rheumatoid arthritis (RA). We...
Individuals at risk of rheumatoid arthritis (RA) demonstrate systemic autoimmunity in the form anti-citrullinated peptide antibodies (ACPA). MicroRNAs (miRNAs) are implicated established RA. This study aimed to (1) compare miRNA expression between healthy individuals and those that develop RA, (2) evaluate change from "at-risk" early RA (3) explore whether these miRNAs could inform a signature predictive progression We performed global profiling 754 per patient on matched serum sample cohort...
TNFAIP3 encodes the NF-κB regulatory protein A20. High-penetrance heterozygous mutations in cause a haploinsufficiency of A20 (HA20), inadequate inhibition pathway, and an early onset autoinflammatory disorder. However, clinical phenotype patients with HA20 varies greatly diagnoses prior to establishing genetic cause, included both autoimmune conditions. Here, we present first patient HA20, who was previously diagnosed AOSD but later found have novel variant successfully treated anti-IL6...
IκB kinase α (IKKα) is part of the cytoplasmic IKK complex regulating nuclear factor-κB (NF-κB) release and translocation into nucleus in response to pro-inflammatory signals. IKKα can also be recruited directly promoter NF-κB-dependent genes by NF-κB where it phosphorylates histone H3 at serine 10, triggering recruitment bromodomain-containing protein 4 positive transcription elongation factor b. Herein, we report that travels with elongating form ribonucleic acid polymerase II together...
Differentiation is a multistep process tightly regulated and controlled by complex transcription factor networks. Here, we show that the rate of differentiation common myeloid precursor cells increases after depletion CTCF, protein emerging as potential key regulating higher-order chromatin structure. We identified CTCF binding in vicinity important factors showed impacts on expression these genes concordance with observed acceleration commitment. Furthermore, loss histone variant H2A.Z...
The transcriptional activation of the chicken lysozyme gene (cLys) by lipopolysaccharide (LPS) in macrophages is dependent on transcription a LPS-Inducible Non-Coding RNA (LINoCR) triggering eviction CCCTC-binding factor (CTCF) from negative regulatory element upstream start site. LINoCR transcribed promoter originally characterized as hormone response enhancer oviduct. Herein, we report characterization this cis-regulatory (CRE). In activated macrophages, 60 bp region bound NF-κB, AP1 and...
Abstract Adoptive cell therapy (ACT) using ex vivo expanded tumor infiltrating lymphocytes (TIL) has shown great promise as a treatment for metastatic melanoma and the potential to deliver durable responses in other solid tumors. Clonal neoantigens, which are derived from mutations occurring very early development, present all cancer cells within patient therefore could be optimal targets TIL-based therapies. Recently it was that number of clonal neoantigens is associated with improved...
<h3>Background and Objectives</h3> Rheumatoid arthritis (RA) is a polygenic disorder usually arising from combined genetic predisposition environmental influences with associated dysfunctional immune responses. The X-box binding protein 1 (XBP1) transcription factor central regulator of the endoplasmic reticulum (ER) stress response. It induced via activation IRE1 sensor as part unfolded response (UPR) has been implicated in several diseases processes including RA. XBP1 can also be activated...
<h3>Background and objectives</h3> Recent EULAR recommendations for terminology of rheumatoid arthritis (RA) at-risk groups recognise those with systemic autoimmunity associated pre-clinical RA, characterised by the presence ACPA. Identification predictors progression from this pre-RA state to RA syndrome would have clinical utility. MicroRNA (miRNA) are highly conserved small, non-coding RNA that serve as transcriptional negative regulators; growing evidence they contribute pathogenesis...
<h3>Background and objectives</h3> Rheumatoid arthritis (RA) arises in individuals with a genetic predisposition, triggered by environmental influences, leading to dysfunctional immune responses. The importance of pro-inflammatory cytokines, such as TNF IL-6, RA is well recognised, the successful use biologic agents inhibiting their action widely established. study intracellular effect cytokine ligation receptors interest elucidating mechanisms potentially response prediction. This project...
<h3>Background</h3> Recent EULAR [1] recommendations for terminology of rheumatoid arthritis (RA) at-risk groups recognise those with systemic autoimmunity associated pre-clinical RA, characterised by the presence ACPA. Identification predictors progression from this pre-RA state to RA syndrome would have clinical utility. We reported on a number potential and imaging markers [2]. MicroRNA (miRNA) are highly conserved small, non-coding RNA that serve as transcriptional negative regulators;...
<h3>Background</h3> We previously reported increased constitutive but unchanged induced CD4+ p-STAT3 in established RA versus healthy control (HC).<sup>1</sup> This study aims to evaluate early (ERA) (i) cell-subset and Cis (IL-6) Trans (IL-6/sIL6R)-induced IL-6 signalling (ii) effect of tocilizumab (TCZ; +/-MTX) (iii) for an association between baseline phosphorylation intensities TCZ (+/- MTX) response. <h3>Materials methods</h3> Multiparameter phosphoflow cytometry was performed on 20...
<h3>Introduction</h3> B-cells have a well-established role in the pathogenesis of rheumatoid arthritis (RA), illustrated by successful treatment RA with B-cell depletion therapy.<sup>1</sup>Sialic acid (SA) is 9-carbon backbone sugar involved many immune system functions including cell migration, adhesion and activation.<sup>2</sup> In RA, sialylation surface, membrane bound IgM, has been found to differ from healthy control B-cells. These changes attributed alterations antibody...
<h3>Introduction</h3> Rheumatoid arthritis (RA) is a chronic, inflammatory that evolves along an immunological and disease continuum. The era of targeted biological therapies has been transformative; however, significant unmet need the effective tailoring therapy to deliver optimal treatment responses. In addition, concept window opportunity well-recognised whereby early commencement confers improved outcomes compared delayed treatment. importance pro-inflammatory cytokines TNF IL-6 in...
<h3>Career situation of first and presenting author</h3> Student for a master or PhD. <h3>Introduction</h3> Sialic acids are family 9-carbon sugars, added to the termini glycoprotein chains, which present on surface many cells, secreted proteins.<sup>1</sup> glycan chains Fc fragment IgG molecules can affect how binds receptors.<sup>2</sup> In RA other autoimmune conditions, disease specific auto-antibodies display decreased sialylation compared with normal IgG.<sup>3</sup> It has also been...