A5062739895- Lymphoma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- Celiac Disease Research and Management
- Viral-associated cancers and disorders
- Acute Myeloid Leukemia Research
- Genetic factors in colorectal cancer
- HIV Research and Treatment
- Microscopic Colitis
- Autophagy in Disease and Therapy
- CAR-T cell therapy research
- Cutaneous lymphoproliferative disorders research
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Mast cells and histamine
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- SARS-CoV-2 and COVID-19 Research
- Reproductive System and Pregnancy
- Cancer, Hypoxia, and Metabolism
- Influenza Virus Research Studies
- Cell Image Analysis Techniques
- Ubiquitin and proteasome pathways
University of Cambridge
2001-2025
Cambridge University Hospitals NHS Foundation Trust
2021-2024
Addenbrooke's Hospital
2001-2021
University of Oxford
2010-2020
John Radcliffe Hospital
2008-2019
Oxford University Hospitals NHS Trust
2015-2019
Royal Hallamshire Hospital
2017
Sheffield Teaching Hospitals NHS Foundation Trust
2017
Nuffield Orthopaedic Centre
2015-2016
University of Liverpool
2016
The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) can be proteolytically activated by cathepsins B and L upon viral uptake into target cell endosomes. In contrast, it is largely unknown whether host proteases located in secretory pathway infected cells and/or on surface cleave SARS S. We along with others could previously show that type II transmembrane protease TMPRSS2 activates influenza virus hemagglutinin human metapneumovirus F cleavage. Here, we...
The role of autophagy, a lysosomal degradation pathway which prevents cellular damage, in the maintenance adult mouse hematopoietic stem cells (HSCs) remains unknown. Although normal HSCs sustain life-long hematopoiesis, malignant transformation leads to leukemia. Therefore, mechanisms protecting from damage are essential prevent malignancies. In this study, we crippled autophagy by conditionally deleting gene Atg7 system. This resulted loss HSC functions, severe myeloproliferation, and...
DC-SIGN is a C-type lectin, highly expressed on the surface of immature dendritic cells (DCs), that mediates efficient infection T in trans by its ability to bind HIV-1, HIV-2, and SIV. In addition, adhesion molecules surfaces naïve endothelium also suggests involvement T-cell activation DC trafficking. To gain further insights into range expression potential functions DC-SIGN, we performed detailed analysis adult fetal tissues analyzed regulated cultured DCs macrophages. First, show...
The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses the SARS-coronavirus (TMPRSS2) in cell culture may play an important role viral spread pathogenesis infected host. However, it is at present largely unclear to what extent these are expressed target cells human tissues. Here, we show that both coexpressed with 2,6-linked sialic acids, major receptor determinant of viruses, throughout respiratory tract. Similarly, coexpression ACE2, receptor, was frequently...
The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) poses a constant threat to human health. viral spike protein (SARS-S) mediates host cell entry and is potential target for antiviral intervention. Activation of SARS-S by proteases essential SARS-CoV infectivity but remains incompletely understood. Here, we analyzed the role type II transmembrane serine (TTSPs) airway trypsin-like protease (HAT) protease, 2 (TMPRSS2), in activation. We found that HAT activates...
DC-SIGN, a C-type lectin expressed on the surface of dendritic cells (DCs), efficiently binds and transmits HIVs simian immunodeficiency viruses to susceptible in trans. A DC-SIGN homologue, termed DC-SIGNR, has recently been described. Herein we show that like can bind multiple strains HIV-1, HIV-2, virus transmit these both T cell lines human peripheral blood mononuclear cells. Binding DC-SIGNR was dependent carbohydrate recognition. Immunostaining with DC-SIGNR-specific antiserum showed...
Abstract DC-SIGN is a C-type lectin, expressed on dendritic cell subset. It able to bind ICAM3 and HIV gp120 in calcium-dependent manner. Here we report the genomic organization of map it chromosome 19p13 adjacent lectin CD23 (FcεRII). We also novel, closely linked gene, DC-SIGNR, which shows 73% identity at nucleic acid level similar organization. Proteins encoded by both genes have tracts repeats 23 aa, predicted form coiled coil neck region. They possess motifs that are known mannose...
Platelets can engulf human immunodeficiency virus type 1 (HIV-1), and a significant amount of HIV-1 in the blood infected individuals is associated with these cells. However, it unclear how platelets capture whether platelet-associated remains infectious. DC-SIGN other lectins contribute to by dendritic cells (DCs) facilitate spread DC/T-cell cocultures. Here, we show that express both C-type lectin-like receptor 2 (CLEC-2) low levels DC-SIGN. CLEC-2 bound HIV-1, irrespective presence viral...
ABSTRACT Proteolysis of influenza virus hemagglutinin by host cell proteases is essential for viral infectivity, but the responsible are not well defined. Recently, we showed that engineered expression type II transmembrane serine (TTSPs) TMPRSS2 and TMPRSS4 allows (HA) cleavage. Here analyzed whether expressed in target cells support spread absence exogenously added protease (trypsin). We found transient resulted HA cleavage trypsin-independent spread. Endogenous lines correlated with...
Decreased autophagy contributes to malignancies, however it is unclear how impacts on tumour growth. Acute myeloid leukemia (AML) an ideal model address this as (i) patient samples are easily accessible, (ii) the hematopoietic stem and progenitor population (HSPC) where transformation occurs well characterized, (iii) loss of key gene Atg7 in cells (HSPCs) leads a lethal pre-leukemic phenotype mice. Here we demonstrate that Atg5 results identical HSPC Atg7, confirming general role for...
Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal TRM remains undefined. Here, we investigate functional through study donor-derived from transplant recipients. Single-cell profiling identifies two states CD8+ cells, delineated by ITGAE ITGB2 expression. We define a signature discriminating these populations, including differential expression cytotoxicity-...
Abstract Autophagy is an important cellular degradation pathway with a central role in metabolism as well basic quality control, two processes inextricably linked to ageing. A decrease autophagy associated increasing age, yet it unknown if this causal the ageing process, and whether restoration can counteract these effects. Here we demonstrate that systemic inhibition induces premature acquisition of age-associated phenotypes pathologies mammals. Remarkably, provides near complete recovery...
Objectives To investigate whether people with coeliac disease are at increased risk of cardiovascular disease, including ischaemic heart myocardial infarction, and stroke. Design Prospective analysis a large cohort study. Setting UK Biobank database. Participants 469 095 adults, which 2083 had aged 40-69 years from England, Scotland, Wales between 2006 2010 without baseline. Main outcome measure A composite primary was relative stroke in compared who do not have assessed using Cox...
Abstract MYC translocation occurs in 8–14% of diffuse large B-cell lymphoma (DLBCL), and may concur with BCL2 and/or BCL6 translocation, known as double-hit (DH) or triple-hit (TH). DLBCL- / -DH/TH are largely germinal centre like subtype, but show variable clinical outcome, IG :: fusion significantly associated inferior survival. While -DH their cell-of-origin subtypes outcome. Intriguingly, only 40-50% DLBCL high protein expression (>70%). We studied 186 DLBCLs including 32...
BackgroundThe diagnosis of celiac disease (CD), an autoimmune disorder with estimated global prevalence around 1%, generally relies on the histologic examination duodenal biopsies. However, interpathologist agreement for CD is at no more than 80%. We aim to improve by developing accurate, machine-learning-based diagnostic classifier.MethodsWe present a machine learning model that diagnoses presence or absence from set biopsies representative real-world clinical data. Our was trained diverse...
ABSTRACT DC-SIGN is a C-type lectin expressed on dendritic cells and restricted macrophage populations in vivo that binds gp120 acts trans to enable efficient infection of T by human immunodeficiency virus type 1 (HIV-1). We report here DC-SIGN, when cis with CD4 coreceptors, allowed more both HIV simian (SIV) strains, although the extent varied from 2- 40-fold, depending strain. Expression target did not alleviate requirement for or coreceptor viral entry. Stable expression multiple...
Abstract Mechanisms of transplacental transmission human immunodeficiency virus (HIV) are poorly understood. DC‐SIGN is a C‐type lectin able to bind HIV gp120 with high affinity, mediating adsorption the surface dendritic cells for up several days. Via this mechanism, significantly enhances infection CD4 + co‐receptor (CCR5 or CXCR4) T lymphocytes in trans . In study, DC‐SIGN‐specific serum was developed investigate cell type responsible level RNA expression previously observed placenta....
The role of DC-SIGN on human rectal mucosal dendritic cells is unknown. Using highly purified DC-SIGN+ and an ultrasensitive real-time reverse transcription-PCR assay to quantify virus binding, we found that HLA-DR+/DC-SIGN+ can bind transfer more than the HLA-DR+/DC-SIGN- cells. Greater 90% bound total mononuclear (MMCs) was accounted for by cells, which comprise only 1 5% MMCs. Significantly, anti-DC-SIGN antibodies blocked binding when more-physiologic amounts inoculum were used....
Genome-wide association studies (GWAS) have identified over 40 loci that affect risk of coronary artery disease (CAD) and the causal mechanisms at majority are unknown. Recent suggested many GWAS variants influence through altered transcriptional regulation in disease-relevant cell types. We explored changes during a key pathophysiological event CAD, environmental lipid-induced transformation macrophages to lipid-laden foam cells. used combination open chromatin mapping with...
Dendritic cells are potent antigen-presenting that express several membrane lectins, including the mannose receptor and DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin). To identify highly specific ligands for these dendritic cell receptors, oligosaccharides were converted into glycosynthons (Os1) used to prepare oligolysine-based glycoclusters, Os-[Lys(Os)]n-Ala-Cys-NH2. Clusters containing two six dimannosides as well clusters four or five pentasaccharides (Lewisa Lewisx)...
The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis FOXP1-silenced DLBCL cell lines identified differential regulation immune response signatures and major histocompatibility complex class II (MHC II) genes as some the most significant differences between germinal center (GCB)-like with full-length protein expression versus activated (ABC)-like expressing predominantly short isoforms. In an...