A5090516247- Immune Cell Function and Interaction
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- Immune responses and vaccinations
- SARS-CoV-2 and COVID-19 Research
- IL-33, ST2, and ILC Pathways
- Autoimmune and Inflammatory Disorders Research
- Inflammasome and immune disorders
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Long-Term Effects of COVID-19
- CAR-T cell therapy research
- Spondyloarthritis Studies and Treatments
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Viral gastroenteritis research and epidemiology
- RNA Research and Splicing
- Macrophage Migration Inhibitory Factor
- Agriculture and Biological Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nanoplatforms for cancer theranostics
- interferon and immune responses
- Adenosine and Purinergic Signaling
University of Oxford
2017-2025
Churchill Hospital
2020-2025
MRC Weatherall Institute of Molecular Medicine
2018-2024
Centre for Human Genetics
2018-2024
Nuffield Orthopaedic Centre
2021
Cancer Research UK Oxford Centre
2021
Cardiff University
2020-2021
Oxford BioMedica (United Kingdom)
2020
MRC Human Immunology Unit
2017
John Radcliffe Hospital
2017
Neutrophils are critical and short-lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic nuclear remodeling, but processes governing these energy-consuming changes unknown. While previous studies show autophagy is required for other blood cell lineages, its function during granulopoiesis has remained elusive. Here, we have shown metabolism developmentally programmed essential neutrophil vivo....
Abstract IL-7 is a key factor in T cell immunity and common variants at IL7R , encoding its receptor, are associated with autoimmune disease susceptibility. mRNA induced stimulated monocytes, yet function for monocyte biology remains unexplored. Here we characterize genetic regulation of the protein level healthy individuals, find that surface soluble (sIL7R) markedly by lipopolysaccharide. In both sIL7R expression strongly associate allelic carriage rs6897932, disease-associated...
Abstract Membrane ion channels of the calcium homeostasis modulator (CALHM) family promote cell–cell crosstalk at neuronal synapses via ATP release, where acts as a neurotransmitter. CALHM6, only CALHM highly expressed in immune cells, has been linked to induction natural killer (NK) cell anti‐tumour activity. However, its mechanism action and broader functions system remain unclear. Here, we generated Calhm6 −/− mice report that CALHM6 is important for regulation early innate control...
Significance The NLRP3 inflammasome is an innate sensor activated by signals released from pathogens or injured tissues. Activation of the can be beneficial during infection and vaccination. Nonetheless, when activity uncontrolled chronic it becomes detrimental contributes to inflammation-driven pathology in several diseases. Licensing mechanisms must exist that prevent unwanted responses. Here, we characterize one such mechanism. We describe TBK1 IKKε, two closely related kinases upon TLR...
Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and implicated autoimmune pathogenesis. The degree to which regulatory variants affect cell gene expression is poorly understood. Here we perform quantitative trait locus mapping of negatively selected from a population healthy Europeans (n = 245). We find significant subset genes demonstrate loci specific these highly informative human disease, particular autoimmunity. A transcriptome-wide association study...
Abstract Cytomegalovirus (CMV) is a globally endemic latent herpes virus that profoundly impacts T cell immunity. We investigated the oncological consequences of CMV infection across 341 prospectively recruited patients receiving immune checkpoint blockade (ICB) for melanoma. + with metastatic melanoma (MM) have higher lymphocyte counts, reduced neutrophil to ratio and divergent CD8 gene expression. Combination anti-CTLA-4/anti-PD-1 ICB, but not single-agent anti-PD-1 induces cytotoxicity...
Abstract IL-7 is a key factor in T-cell immunity and IL7R polymorphisms are implicated autoimmune pathogenesis. mRNA induced stimulated monocytes genetically determined manner, yet role for monocyte biology remains unexplored. Here we characterize genetic regulation of at the protein level across multiple cell subsets conditions healthy individuals. We find surface soluble (sIL7R) markedly expressed response to lipopolysaccharide (LPS). further demonstrate alleles rs6897932, non-synonymous...
ABSTRACT Clinical responses to immune checkpoint blockade (ICB) for metastatic melanoma (MM) are variable, with patients frequently developing related adverse events (irAEs). The role played by myeloid populations in modulating ICB remains poorly defined. We explored the effect of MM and response across a cohort (n=116) healthy donors (n=45) using bulk single cell RNA-seq, flow cytometry. Monocytes from exhibit highly dysregulated baseline transcriptional profiles, whilst treatment elicits...
<title>Abstract</title> Insights into variation in monocyte context-specific splicing and transcript usage are limited. We have performed paired gene QTL mapping across distinct immune states using RNA-seq of monocytes isolated from a cohort 185 healthy Europeans incubated alone or the presence IFNγ lipopolysaccharide (LPS). identify regulatory variants to 5,749 genes 8,727 transcripts, with 291 tQTL colocalising GWAS loci (PP.H4 > 0.8). Notable disease relevant associations 0.99) include...
Summary Paragraph The relationship between chronic viral infection and cancer response to immune checkpoint blockade (ICB) is poorly understood. Cytomegalovirus (CMV) globally endemic causes severe disease in the immunocompromised. In immunocompetent individuals clinical effects of CMV are an area active investigation. Here, analysis 396 patients receiving ICB for cancer, we investigate oncological immunological consequences seropositivity. We find that with leads profound skewing CD8 + T...
Abstract Natural Killer (NK) cells are innate lymphocytes with central roles in immunosurveillance and implicated autoimmune pathogenesis. The degree to which regulatory variants affect NK gene expression is poorly understood. We performed quantitative trait locus (eQTL) mapping of negatively selected from a population healthy Europeans (n=245). find significant subset genes demonstrate eQTL specific these highly informative human disease, particular autoimmunity. An cell transcriptome-wide...
Abstract DNA methylation (DNAm) has pervasive effects on gene expression and associations with ageing-related traits. Here we describe monocyte DNAm responses to inflammatory stimuli across 192 individuals. We find that, unlike the similarly widespread changes in elicited by LPS IFN γ , is markedly more sensitive LPS. Exposure caused differential at 20,858 immune-modulated CpGs (imCpGs) which display distinct genomic localisation transcription factor usage, dependent upon whether lost or...
<h3>Background</h3> Interleukin 7 (IL-7) plays a key role in T cell survival and proliferation. Both cell-surface expressed soluble forms of the IL-7 receptor (sIL7R) are recognised. sIL7R has been shown to prolong activity inflammation(.<sup><sup>1</sup></sup> IL7R polymorphisms associated with multiple inflammatory diseases including ankylosing spondylitis(AS). Higher levels circulating present those carrying risk variant but cellular sources unclear. Expression quantitative trait loci...