A5088575178- Autoimmune and Inflammatory Disorders Research
- Rheumatoid Arthritis Research and Therapies
- Lymphoma Diagnosis and Treatment
- Systemic Lupus Erythematosus Research
- Adolescent and Pediatric Healthcare
- Coronary Interventions and Diagnostics
- Immune Cell Function and Interaction
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Family and Disability Support Research
- Inflammasome and immune disorders
- Cytokine Signaling Pathways and Interactions
- Acute Lymphoblastic Leukemia research
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Ocular Diseases and Behçet’s Syndrome
- Musculoskeletal Disorders and Rehabilitation
- Mycobacterium research and diagnosis
- Autism Spectrum Disorder Research
- S100 Proteins and Annexins
- DNA Repair Mechanisms
- Cardiac Imaging and Diagnostics
- Immune cells in cancer
- T-cell and B-cell Immunology
- Blood transfusion and management
Versus Arthritis
2014-2025
University of Manchester
2016-2025
NIHR Manchester Biomedical Research Centre
2025
Ochsner Medical Center
2025
Genomics (United Kingdom)
2015-2024
Manchester Academic Health Science Centre
2014-2024
ING Direct
2023
Louisiana State University
1995-2021
University of Bergen
2021
Yale University
2019-2021
Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cells, and mouse model advanced atherosclerosis, investigated intraplaque hemorrhage on function with respect angiogenesis, vascular permeability,...
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...
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region strongly associated with JIA. Fine-mapping was performed look for similarities differences in HLA associations between define correspondences adult inflammatory arthritides.Dense genotype from region, Immunochip array 5043 cases 14...
A single nucleotide polymorphism (SNP) at 10q11 (rs10993994) in the 5′ region of MSMB gene was recently implicated prostate cancer risk two genome-wide association studies. To identify possible causal variants region, we genotyped 16 tagging SNPs and imputed 29 additional ∼65 kb genomic a Swedish population-based case–control study (CAncer Prostate Sweden), including 2899 cases 1722 controls. We found evidence for independent loci, separated by recombination hotspot, associated with risk....
Biologic drug therapies represent a huge advance in the treatment of rheumatoid arthritis (RA). However, very good disease control is achieved only 30% patients, making identification biomarkers response research priority. We undertook this study to test our hypothesis that differential DNA methylation patterns may provide predictive tumor necrosis factor inhibitor (TNFi) therapy patients with RA.An epigenome-wide association was performed on pretreatment whole blood from RA. Patients who...
Juvenile idiopathic arthritis (JIA) comprises 7 heterogeneous categories of chronic childhood arthritides. Approximately 5% children with JIA have rheumatoid factor (RF)-positive arthritis, which phenotypically resembles adult (RA). Our objective was to compare and contrast the genetics RF-positive polyarticular those RA selected other categories, more fully understand pathophysiologic relationships inflammatory arthropathies.Patients (n = 340) controls 14,412) were genotyped using...
Approximately 30-40% of rheumatoid arthritis (RA) patients who are initially started on low-dose methotrexate (MTX) will not benefit from the treatment. To date, no reliable biomarkers MTX inefficacy in RA have been identified. The aim this study was to analyze whole blood samples at 2 time points (pretreatment and 4 weeks following initiation MTX), identify gene expression response.RA were about commence treatment with selected Rheumatoid Arthritis Medication Study. Using European League...
The herpes simplex virus 1 (HSV-1) virion DNA contains nicks and gaps, in this study a novel assay for estimating the size number of gaps was developed. Consistent with previous reports, we estimate that there are approximately 15 per genome, calculate average gap length to be 30 bases. Virion isolated treated DNA-modifying enzymes order fill modify ends. Interestingly, filling blunting ends, or adding random sequences 3' ends DNA, producing flaps, did not impair infectivity following...
Peter Wildy first observed genetic recombination between strains of HSV in 1955. At the time, knowledge DNA repair mechanisms was limited, and it has only been last decade that particular damage response (DDR) pathways have examined context viral infections. One reports addressing interaction a cellular DDR protein HSV-1 observation by Lees-Miller et al. DNA-dependent kinase catalytic subunit levels were depleted an ICP0-dependent manner during Herpes simplex virus 1 infection. Since then,...
Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment early JIA, novel methods machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; iii) compare existing response measures.
Early identification and antimicrobial susceptibility testing (AST) of bloodstream pathogens are important for promptly determining the appropriate therapy. Currently, positive blood culture results (identification AST) reported in 2 to 4 days. The T2Resistance (T2R) Panel (T2 Biosystems, Inc) uses DNA amplification with magnetic resonance from 3 mL whole direct detection 13 antibiotic resistance genes: bla KPC, NDM, VIM, IMP, OXA-48, CTX-M-14/15, AmpC CMY/DHA, vanA/B, mecA/C. We compared...
Acetaldehyde is known to form covalent adducts with tubulin and inhibit microtubule formation. Available evidence indicates that lysine residues are prominently involved in adduct Previous work has shown lysines on can be divided into two general classes based upon their reactivity toward acetaldehyde; those of normal ("bulk" lysines) a highly reactive (HRL) located the alpha-polypeptide subunit. We took advantage fact HRL unreactive when differentiate effects bulk from polymerization. Under...
7012 Background: Isocitrate dehydrogenase-1 ( IDH1 + ) mutations are present in 5-15% of myeloid malignancies, promoting leukemogenesis through production the oncometabolite 2-hydroxyglutarate resulting arrested differentiation. malignancies demonstrate increased reliance on anti-apoptotic protein BCL-2, enhancing susceptibility to BCL-2 inhibitor venetoclax (VEN). We report an interim safety and efficacy analysis ivosidenib (IVO; 500 mg PO daily D15-continuous) combined with VEN (D1-14) +/-...
ABSTRACT Herpes simplex virus 1 (HSV-1) is a double-stranded DNA that replicates in the nucleus of host cell and known to interact with several components cellular DNA-damage-signaling machinery. We have previously reported damage response kinase, ATR, specifically inactivated HSV-1-infected cells. On other hand, we also shown ATR its scaffolding protein, ATRIP, are recruited viral replication compartments, where they play beneficial roles during HSV-1 replication. In order better understand...
The "very late" clinical outcomes for durable polymer drug-eluting stents and bare metal (BMSs) have been shown to be dissimilar in studies. Conceptually, the long-term vascular compatibility of BMSs is still regarded superior stents; however, no pathologic study date has specifically addressed this issue. We evaluated very late (≥1 year) responses (cobalt-chromium [CoCr] everolimus-eluting [EESs] stainless steel sirolimus-eluting [SS-SESs]) versus (CoCr-BMSs).From CVPath stent registry, we...
Objective- Drug-eluting stents eluting canonical mTOR (mammalian target of rapamycin) inhibitors are widely used to treat coronary artery disease but accelerate the development atherosclerosis within stent (neoatherosclerosis)-a leading cause late failure. We recently showed that bind FKBP12.6 (12.6-kDa FK506-binding protein 12), displace it from calcium release channels, resulting in activation PKCα (protein kinase Cα) and dissociation p-120-catenin (p120) VE-CAD (vascular endothelial...
Abstract CD4+ T-cells represent a heterogeneous collection of specialised sub-types and are key cell type in the pathogenesis many diseases due to their role adaptive immune system. By investigating at single level, using RNA sequencing (scRNA-seq), there is potential identify specific states driving disease or treatment response. However, impact depth numbers, two important factors scRNA-seq, has not been determined for complex population such as T-cells. We therefore generated high depth,...
Juvenile idiopathic arthritis (JIA) is a heterogeneous disease, the signs and symptoms of which can be summarised with use composite disease activity measures, including clinical Arthritis Disease Activity Score (cJADAS). However, clusters children young people might experience different global patterns in their run parallel or diverge over time. We aimed to identify such 3 years after diagnosis JIA. The identification these would allow for greater understanding progression JIA, how...
Herpes Simplex Virus type 1 (HSV-1) has evolved to disable the cellular DNA damage response kinase, ATR. We have previously shown that HSV-1-infected cells are unable phosphorylate ATR substrate Chk1, even under conditions in which replication forks stalled. Here we report HSV-1 single stranded binding protein (ICP8), and helicase/primase complex (UL8/UL5/UL52) form a nuclear transfected is necessary sufficient signaling. This localizes sites of colocalizes with ATR/ATRIP RPA, but these...
Background Ossabaw pigs are unique miniature swine with genetic predisposition to develop metabolic syndrome and coronary atherosclerosis after extended periods receiving atherogenic diets. We have hypothesized that transgenic expressing chimp PCSK9 (proprotein convertase subtilisin‐like/kexin type 9) containing the D374Y gain of function would familial hypercholesterolemia artery plaques more rapidly than Landrace same transgene. Methods Results gain‐of‐function founders were generated by...