A5084741024- Inflammatory Bowel Disease
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Mast cells and histamine
- MicroRNA in disease regulation
- Zebrafish Biomedical Research Applications
- Nicotinic Acetylcholine Receptors Study
- Immune Response and Inflammation
- High Altitude and Hypoxia
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hemoglobin structure and function
- IL-33, ST2, and ILC Pathways
- Tryptophan and brain disorders
- Neurotransmitter Receptor Influence on Behavior
- Metabolism and Genetic Disorders
- Phagocytosis and Immune Regulation
- Eosinophilic Esophagitis
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Immune Cell Function and Interaction
- Sports injuries and prevention
- Sustainable Finance and Green Bonds
- Pancreatic and Hepatic Oncology Research
- Cancer, Stress, Anesthesia, and Immune Response
- Monoclonal and Polyclonal Antibodies Research
University of Sheffield
2012-2024
Queen Mary University of London
2014-2024
University of Wisconsin–Madison
2024
Leverhulme Trust
2023
Queen's Hospital
2021-2022
Queensland Academy of Sport
2022
Evolva (Denmark)
2021
University College Hospital
2018
University College London
2018
Immunité et Cancer
2016
Abstract Cryptococcus neoformans is a significant fungal pathogen of immunocompromised patients. Many questions remain regarding the function macrophages in normal clearance cryptococcal infection and defects present uncontrolled cryptococcosis. Two current limitations are: 1) The difficulties interpreting studies using isolated context progression infection, 2) use high resolution imaging understanding immune cell behavior during animal infection. Here we describe high-content method...
Intestinal fibrosis with stricture formation is a complication of CD (Crohn's disease) that may mandate surgical resection. Accurate biomarkers reflect the relative contribution to an individual are unmet need in managing patients CD. The miRNA-29 (miR-29) family has been implicated cardiac, hepatic and pulmonary fibrosis. In present study, we investigated expression miR-29a, miR-29b miR-29c mucosa overlying (SCD) paired from non-strictured areas (NSCD). There was significant down-regulation...
Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal essential limiting tissue damage. Here, we have identified a critical role the prolyl hydroxylase enzyme Phd2 in maintaining balance between appropriate, predominantly neutrophil-mediated pathogen clearance resolution of response. We demonstrate that myeloid-specific loss resulted an exaggerated inflammatory response Streptococcus pneumonia, with increases...
Drug-resistant mycobacteria are a rising problem worldwide. There is an urgent need to understand the immune response tuberculosis identify host targets that, if targeted therapeutically, could be used tackle these currently untreatable infections. In this study we use Il-1β fluorescent transgenic line show that there early innate proinflammatory well-established zebrafish models of inflammation and Mycobacterium marinum infection. We demonstrate host-derived hypoxia signaling, mediated by...
Infection outcomes are regulated by neutrophil responses to oxygen and nutrient availability.
We explored the role of Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 pancreatic β cells (Fh1βKO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression mitochondrial or cytosolic FH not deletion Hif1α Nrf2. Progressive hyperglycemia Fh1βKO mice led to dysregulated metabolism cells, a decrease glucose-induced ATP production, electrical activity,...
Development of fibrosis and subsequent stricture formation in Crohn's disease (CD) increases morbidity rates surgery reduces patients' quality life. There are currently no biomarkers intestinal that might allow earlier identification better management patients at increased risk formation. MicroRNA profiling serum from CD was used to identify microRNAs associated with Differential expression miR-19a-3p miR-19b-3p validated by quantitative PCR independent cohort stricturing nonstricturing (n =...
Solid tumours have oxygen gradients and areas of near almost total anoxia. Hypoxia reduces sensitivity to 5-fluorouracil (5-FU)-chemotherapy for colorectal cancer (CRC). MicroRNAs (miRNAs) are hypoxia sensors were altered consistently in six CRC cell lines (colon cancer: DLD-1, HCT116 HT29; rectal HT55, SW837 VACO4S) maintained (1 0.2% oxygen) compared with normoxia (20.9%). also showed amino acid metabolism hypoxia-responsive miRNAs predicted target genes four pathways: beta-alanine;...
Macrophage phenotypes are poorly characterised in disease systems vivo. Appropriate macrophage activation requires complex coordination of local microenvironmental cues and cytokine signalling. If the molecular mechanisms underpinning were better understood, macrophages could be pharmacologically tuned during situations. Here, using zebrafish tnfa:GFP transgenic lines as vivo readouts, we show that physiological hypoxia stabilisation Hif-1 promotes tnfa expression. We demonstrate a new...
Abstract Single cell RNA sequencing of human full thickness Crohn's disease (CD) small bowel resection specimens was used to identify potential therapeutic targets for stricturing (S) CD. Using an unbiased approach, 16 lineages were assigned within 14,539 sequenced cells from patient‐matched SCD and non‐stricturing (NSCD) preparations. NSCD contained identical types. Amongst immune cells, B plasma selectively increased in samples. subsets suggested formation tertiary lymphoid tissue compared...
Intestinal fibrosis and stricture formation is an aggressive complication of Crohns disease (CD), linked to increased morbidity costs. The present study investigates the contribution Wingless-Int-1 (Wnt) signalling intestinal fibrogenesis, considers potential cross-talk between Wnt transforming growth factor β1 (TGFβ) pathways, assesses therapeutic small-molecule inhibitors. β-catenin expression was explored by immunohistochemistry (IHC) in formalin-fixed paraffin embedded (FFPE) tissue from...
Abstract Intestinal mesenchymal cells deposit extracellular matrix in fibrotic Crohn's disease (CD). The contribution of epithelial to transition (EMT) the cell pool CD fibrosis remains obscure. miR‐200 family regulates fibrosis‐related EMT organs other than gut. E‐cadherin, cytokeratin‐18 and vimentin expression was assessed using immunohistochemistry on paired strictured (SCD) non‐strictured (NSCD) ileal resections correlated with grade. MiR‐200 measured SCD NSCD tissue compartments laser...
Mast cells (MC) are immune located next to the intestinal epithelium with regulatory function in maintaining homeostasis of mucosal barrier. We have investigated MC activities colon inflammation and cancer mice either wild-type (WT) or MC-deficient (Kit(W-sh)) reconstituted not bone marrow-derived MCs. Colitis was chemically induced dextran sodium sulfate (DSS). Tumors were by administering azoxymethane (AOM) intraperitoneally before DSS. Following DSS withdrawal, Kit(W-sh) showed reduced...
By the capillary-flow method viscosity of liquid tin has been measured over a range temperature just above melting-point. The kinetic-energy correction determined independently by use Knibbs's graphical method. values are in good agreement with measurements Stott, and confirm general accuracy work Sauerwald Töpler. variation value at freezing-point can be adequately represented Andrade's theory liquids.
No effective therapeutic intervention exists for intestinal fibrosis in Crohn's disease [CD]. We characterized fibroblast subtypes, epigenetic and metabolic changes, signalling pathways CD to inform future strategies.
Primary ciliary dyskinesia is an autosomal recessive disorder affecting the motility of cilia. There are a range ultrastructural defects that lead to associated clinical symptoms including ineffective mucus clearance, reduced lung function, infertility, and left-right isomerism. Mutations in radial spoke head proteins known cause primary dyskinesia. Ultrastructually these identified by portion cilia lacking central pair transposed outer microtubular doublets. We have repeatedly observed...
Background It has been suggested that inhibition of monoamine oxidase (MAO) activity by components cigarette smoke may impact on smoking addiction, but it is unclear to what extent the known MAO inhibitors in tobacco cause this inhibition. Methods inhibitory was measured a series particulate matter preparations from different brands and loose-leaf commonly available New Zealand. Results When extracts were diluted contain physiologically relevant nicotine concentration 0.2 μM, all samples...
Multi-drug-resistant tuberculosis is a worldwide problem, and there an urgent need for host-derived therapeutic targets, circumventing emerging drug resistance. We have previously shown that hypoxia-inducible factor-1α (Hif-1α) stabilisation helps the host to clear mycobacterial infection via neutrophil activation. However, Hif-1α has also been implicated in chronic inflammatory diseases caused by prolonged neutrophilic inflammation. Comorbid inflammation can be found together disease...
ABSTRACT Innate immune responses to inflammation and infection are complex represent major challenges for developing much needed new treatments chronic inflammatory diseases drug-resistant infections. To be ultimately successful, the response must balanced allow pathogen clearance without excess tissue damage, processes controlled by pro- anti-inflammatory signals. The roles of signalling in raising an appropriate underappreciated, representing overlooked potential drug targets. This is...