A5051400764- Diabetes and associated disorders
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Diabetes Management and Research
- Circadian rhythm and melatonin
- Mitochondrial Function and Pathology
- Single-cell and spatial transcriptomics
- Pancreatic function and diabetes
- Gene expression and cancer classification
- Photoreceptor and optogenetics research
- Genetic Syndromes and Imprinting
- Genetic Associations and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- T-cell and Retrovirus Studies
- Cancer Genomics and Diagnostics
- Genetic Mapping and Diversity in Plants and Animals
- Metabolism and Genetic Disorders
- Cancer Immunotherapy and Biomarkers
- Cutaneous lymphoproliferative disorders research
- RNA and protein synthesis mechanisms
- Influenza Virus Research Studies
- Bioinformatics and Genomic Networks
- COVID-19 Clinical Research Studies
- Congenital heart defects research
- Birth, Development, and Health
Wellcome Sanger Institute
2022-2024
King's College London
2014-2024
Guy's Hospital
2017-2024
Medical University of Silesia
2016-2023
Górnośląskie Centrum Medyczne
2023
The Francis Crick Institute
2019
Guy's and St Thomas' NHS Foundation Trust
2016-2017
King's College - North Carolina
2017
University College London
2017
Public Library of Science
2017
Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The includes discrete changes in B myelomonocytic cell composition, profoundly altered T phenotypes, selective cytokine/chemokine upregulation SARS-CoV-2-specific...
In development, timing is of the utmost importance, and developmental processes often changes as organisms evolve. human evolution, retardation, or neoteny, has been proposed a possible mechanism that contributed to rise many human-specific features, including an increase in brain size emergence cognitive traits. We analyzed mRNA expression prefrontal cortex humans, chimpanzees, rhesus macaques determine whether neotenic are present at gene level. show transcriptome dramatically remodeled...
Studies in type 1 diabetes indicate potential disease heterogeneity, notably the rate of β-cell loss, responsiveness to immunotherapies, and, limited studies, islet pathology. We sought evidence for different immunological phenotypes using two approaches. First, we defined blood autoimmune response by combinatorial, multiparameter analysis autoantibodies and autoreactive T-cell responses 33 children/adolescents with newly diagnosed diabetes. Multidimensional cluster showed equal-sized...
Abstract During activation, T cells undergo extensive gene expression changes that shape the properties of to exert their effector function. Understanding regulation this process could help explain how genetic variants predispose immune diseases. Here, we mapped effects on (expression quantitative trait loci (eQTLs)) using single-cell transcriptomics. We profiled 655,349 CD4 + cells, capturing transcriptional states unstimulated and three time points cell activation in 119 healthy...
General parameters of selection, such as the frequency and strength positive selection in natural populations or role introgression, are still insufficiently understood. The house mouse (Mus musculus) is a particularly well-suited model system to approach questions, since it has defined history splits into subspecies extensive genome information available. We have used high-density single-nucleotide polymorphism (SNP) typing arrays assess genomic patterns introgression alleles two each M. m....
An innate-like γδ T cell compartment in healthy human breast is described and shown to correlate with remission triple-negative cancer.
Defects in T cell receptor (TCR) repertoire are proposed to predispose autoimmunity. Here we show, by analyzing >2 × 108 TCRB sequences of circulating naive, central memory, regulatory and stem cell-like memory CD4+ subsets from patients with type 1 diabetes healthy donors, that have shorter complementarity-determining region 3s (CDR3), all subsets, introduced increased deletions/reduced insertions during VDJ rearrangement. High frequency short CDR3s is also observed unproductive sequences,...
Identifying cellular functions dysregulated by disease-associated variants could implicate novel pathways for drug targeting or modulation in cell therapies. However, follow-up studies can be challenging if disease-relevant types are difficult to sample. Variants associated with immune diseases point toward the role of CD4+ regulatory T cells (Treg cells). We mapped genetic regulation (quantitative trait loci [QTL]) gene expression and chromatin activity Treg cells, we identified 133...
A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01186-5
In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they implicated destruction of insulin-secreting cells. contrast, disease relevance cell–reactive that detectable circulation, and their relationship to function, not known. Here, we tracked multiple, circulating subsets measured function longitudinally 2 years, starting immediately after diagnosis diabetes. We change cell–specific effector memory expressing CD57 was...
Abstract Person-to-person transmission of SARS-CoV-2 virus has triggered a global emergency because its potential to cause life-threatening Covid-19 disease. By comparison paucisymptomatic clearance by most individuals, been proposed reflect insufficient and/or pathologically exaggerated immune responses. Here we identify consensus peripheral blood signature across 63 hospital-treated patients who were otherwise highly heterogeneous. The core conspicuously blended adaptive B cell responses...
Abstract Motivation Identification of cell populations in flow cytometry is a critical part the analysis and lays groundwork for many applications research discovery. The current paradigm manual time consuming subjective. A common goal users to replace with automated methods that replicate their results. Supervised tools provide best performance such use case, however they require fine parameterization obtain Hence, there strong need are fast setup, accurate interpretable. Results flowLearn...
Type 1 diabetes is characterized by a loss of tolerance to pancreatic β-cell autoantigens and defects in regulatory T-cell (Treg) function. In preclinical models, immunotherapy with MHC-selective, autoantigenic peptides restores immune tolerance, prevents diabetes, shows greater potency when multiple are used. To translate this strategy into the clinical setting, we administered mixture six HLA-DRB1*0401–selective, intradermally patients recent-onset type possessing genotype randomized...
Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at cost broader cell repertoire disruption. We applied genomic DNA-based approach concurrently study the immunoglobulin-heavy (IGH) receptor (TCR) β δ chain loci 95 individuals. Our detected anticipated focusing for IGH repertoire, including expansions clusters related sequences temporally aligned with SARS-CoV-2–specific...
Abstract Aim To examine the hypothesis that quality, magnitude and breadth of helper T‐lymphocyte responses to β cells differ in Type 1 diabetes according diagnosis childhood or adulthood. Methods We studied reactivity against β‐cell autoantigens by measuring production pro‐inflammatory cytokine interferon‐γ anti‐inflammatory interleukin‐10, using enzyme‐linked immunospot assays 61 people with (within 3 months diagnosis, positive for HLA DRB 1*0301 and/or *0401 ), whom 33 were...
Introduction: Location of malignant melanoma lesions depends on environmental, genetic, sociological and demographical factors. Available sources do not provide enough information such dependencies in various populations. There is no data concerning the role socio-demographic factors for population Central Eastern Europe. Aim: The aim this work was to evaluate anatomical location primary lesion correlation patients’ gender age. Material methods: A retrospective analysis medical documentation...
Abstract Aims/hypothesis Antigen-specific therapy aims to modify inflammatory T cell responses in type 1 diabetes and restore immune tolerance. One strategy employs GAD65 conjugated aluminium hydroxide (GAD-alum) take advantage of the helper (Th)2-biasing adjuvant properties alum thereby regulate pathological Th1 autoimmunity. We explored cellular molecular mechanism GAD-alum action setting a previously reported randomised placebo-controlled clinical trial conducted by Type Diabetes...