A5078545864- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Psoriasis: Treatment and Pathogenesis
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- interferon and immune responses
- Inflammasome and immune disorders
- Burkholderia infections and melioidosis
- Asthma and respiratory diseases
- Skin and Cellular Biology Research
- Tracheal and airway disorders
- Mycobacterium research and diagnosis
- Wound Healing and Treatments
- Galectins and Cancer Biology
- Dermatology and Skin Diseases
- Contact Dermatitis and Allergies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune cells in cancer
- Tuberculosis Research and Epidemiology
- Fibroblast Growth Factor Research
- Protein Tyrosine Phosphatases
- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Tryptophan and brain disorders
- PI3K/AKT/mTOR signaling in cancer
Imperial College London
2016-2024
Securboration (United States)
2024
GlaxoSmithKline (United Kingdom)
2021
Lung Institute
2020
The Francis Crick Institute
2014-2016
Tuberculosis, caused by the intracellular bacterium Mycobacterium tuberculosis, currently causes ∼1.4 million deaths per year, and it therefore remains a leading global health problem. The immune response during tuberculosis incompletely understood, particularly regarding factors that are harmful rather than protective to host. Overproduction of type I IFN family cytokines is associated with exacerbated in both mouse models humans, although mechanisms which promotes disease not well...
Inherited and de novo mutations in the CARD14 gene promote development of psoriasis, an inflammatory disease skin. Caspase recruitment domain-containing protein 14 (CARD14) is a member CARMA family that includes structurally related CARD11 adaptor mediates NF-κB activation by antigen receptors. We investigated mechanism which mutation psoriasis activates NF-κB. In contrast with wild-type CARD14, CARD14(E138A) CARD14(G117S) mutants interacted constitutively BCL10 MALT1, triggered BCL10-...
Abstract Pattern recognition receptors detect microbial products and induce cytokines, which shape the immunological response. IL-12, TNF-α, IL-1β are proinflammatory essential for resistance against infection, but when produced at high levels they may contribute to immunopathology. In contrast, IL-10 is an immunosuppressive cytokine, dampens responses, it can also lead defective pathogen clearance. The regulation of these cytokines therefore central generation effective balanced immune this...
The activation of TLRs by microbial molecules triggers intracellular-signaling cascades and the expression cytokines such as IL-10. Il10 is tightly controlled to ensure effective immune responses, while preventing pathology. Maximal TLR-induction transcription in macrophages requires signaling through MAPKs, ERK, p38. Signals via p38 downstream TLR4 also regulate IL-10 at post-transcriptional level, but whether this mechanism operates other not clear. We compared regulation production TLR2...
To investigate how the CARD14E138A psoriasis-associated mutation induces skin inflammation, a knock-in mouse strain was generated that allows tamoxifen-induced expression of homologous Card14E138A from endogenous Card14 locus. Heterozygous rapidly induced acanthosis, immune cell infiltration and pro-inflammatory genes. Homozygous more extensive inflammation severe systemic disease involving myeloid cells in multiple organs, temperature reduction, weight loss organ failure. This phenotype...
The use of human whole blood for transcriptomic analysis has potential advantages over the isolated immune cells studying transcriptional response to pathogens and their products. Whole stimulation can be carried out in a laboratory without expertise or equipment isolate from blood, with added advantage being able undertake experiments using very small volumes blood. Toll like receptors (TLRs) are family pattern recognition which recognise highly conserved microbial Using TLR2 ligand...
Single nucelotide polymorphisms (SNPs) at the
Analysis of the mouse transcriptional response to Listeria monocytogenes infection reveals that a large set genes are perturbed in both blood and tissue these responses enriched for pathways immune response. Further we identified enrichment type I II interferon (IFN) signaling molecules tissues upon infection. Since IFN has been reported widely impair bacterial clearance examined gene expression from wild (WT) IFNαβ receptor-deficient (Ifnar1-/-) mice at basal level with L. monocytogenes....
Rare mutations in CARD14 promote psoriasis by inducing CARD14-BCL10-MALT1 complexes that activate NF-κB and MAP kinases. Here, the downstream signalling mechanism of highly penetrant CARD14E138A alteration is described. In addition to BCL10 MALT1, associated with several proteins important innate immune signalling. Interactions M1-specific ubiquitin E3 ligase HOIP, K63-specific TRAF6 promoted ubiquitination were essential for kinase activation. contrast, binding A20 ABIN1, both genetically...