A5003025313- Inflammatory Bowel Disease
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Immune Cell Function and Interaction
- Helicobacter pylori-related gastroenterology studies
- Gut microbiota and health
- Immune Response and Inflammation
- Microscopic Colitis
- Inflammasome and immune disorders
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- Dermatology and Skin Diseases
- Immunodeficiency and Autoimmune Disorders
- Galectins and Cancer Biology
- T-cell and B-cell Immunology
- Probiotics and Fermented Foods
- Ubiquitin and proteasome pathways
- Celiac Disease Research and Management
- Barrier Structure and Function Studies
- Cytokine Signaling Pathways and Interactions
- Ion Transport and Channel Regulation
- Fibroblast Growth Factor Research
- Child Abuse and Related Trauma
- Legionella and Acanthamoeba research
- Intraperitoneal and Appendiceal Malignancies
AstraZeneca (United Kingdom)
2023-2025
John Radcliffe Hospital
2017-2023
MRC Human Immunology Unit
2017-2023
MRC Weatherall Institute of Molecular Medicine
2019-2023
University of Oxford
2017-2023
Sanofi (United Kingdom)
2023
Case Western Reserve University
2011-2021
Medical Research Council
2019-2020
University School
2012-2016
Digestive Health Research Institute
2014
Gasdermin D (GSDMD) induces pyroptosis via the pore-forming activity of its N-terminal domain, cleaved by activated caspases associated with release IL-1β. Here, we report a nonpyroptotic role full-length GSDMD in guiding IL-1β-containing small extracellular vesicles (sEVs) from intestinal epithelial cells (IECs). In response to caspase-8 inflammasome activation, GSDMD, chaperoned Cdc37/Hsp90, recruits E3 ligase, NEDD4, catalyze polyubiquitination pro-IL-1β, serving as signal for cargo...
Background We previously showed that the probiotic mixture, VSL#3, prevents onset of ileitis in SAMP/YitFc (SAMP) mice, and this effect was associated with stimulation epithelial-derived TNF. The aim study to determine mechanism(s) VSL#3-mediated protection on epithelial barrier function further investigate "paradoxical" effects TNF preventing SAMP ileitis. Methods Permeability evaluated mice prior inflammation during established disease by measuring transepithelial electrical resistance...
Abstract Histology is fundamental to assess two-dimensional intestinal inflammation; however, inflammatory bowel diseases (IBDs) are often indistinguishable microscopically on the basis of mucosal biopsies. Here, we use stereomicroscopy (SM) rapidly profile entire topography and inflammation. We examine surface >700 mice (encompassing >16 strains various IBD-models), create a profiling catalogue 3D-stereomicroscopic abnormalities demonstrate that with comparable histological scores...
Significance Here we demonstrate that IL-1α neutralization reduces the severity of disease in a mouse model Crohn’s disease. Unexpectedly, exerts its antiinflammatory effects by modulating gut microbial ecosystem, and corrected mucosal dysbiosis. Although studies report microbiome affects cytokine production, few have shown specific pivotal such as alters composition function microbiome. The study demonstrates predictive relationship between abundance bacterial species. findings...
Innate lymphoid cells (ILCs) are enriched at barrier surfaces, including the gastrointestinal tract. While most studies have focused on balance between pathogenic group 1 ILCs (ILC1s) and protective ILC3s in maintaining gut homeostasis during chronic intestinal inflammation, such as Crohn's disease (CD), less is known regarding ILC2s. Using an established murine model of CD-like ileitis, i.e., SAMP1/YitFc (SAMP) mouse strain, we showed that ILC2s, compared with ILC1s ILC3s, were increased...
Although regulatory T cells (Tregs) have been implicated in inflammatory bowel disease, Tregs from Crohn's disease (CD) patients are increased number and function normally vitro. To clarify this disparity, we studied Treg vivo using a spontaneous model of CD-like ileitis. We first administered anti-CD25-depleting antibodies to SAMP1/YitFc (SAMP) mice assess ileitis; mesenteric lymph node were then transferred into SCID (severe combined immunodeficient) recipients induce colitis. CD25...
The use of modern endoscopy for research purposes has greatly facilitated our understanding gastrointestinal pathologies. In particular, experimental been highly useful studies that require repeated assessments in a single laboratory animal, such as those evaluating mechanisms chronic inflammatory bowel disease and the progression colorectal cancer. However, methods used across are variable. At least three endoscopic scoring systems have published murine colitis protocols assessment tumors...
Background: Oral involvement is often associated with inflammatory bowel disease (IBD). Recent evidence suggests a high incidence of periodontal in patients Crohn (CD). To the best authors’ knowledge, no animal model IBD that displays was reported previously. The aim this study to investigate occurrence and progression SAMP1/YitFc (SAMP) mice spontaneously develop CD‐like ileitis. In addition, temporal correlation between onset ileitis SAMP studied. Methods: At different time points,...
The use of modern endoscopy for research purposes has greatly facilitated our understanding gastrointestinal pathologies. In particular, experimental been highly useful studies that require repeated assessments in a single laboratory animal, such as those evaluating mechanisms chronic inflammatory bowel disease and the progression colorectal cancer. However, methods used across are variable. At least three endoscopic scoring systems have published murine colitis protocols assessment tumors...
Abstract Background Single-cell technologies enable the fine mapping of disease and treatment mechanisms in inflammatory bowel (IBD). We sought to leverage these insights discover novel drug targets with precise therapeutic hypotheses. To this end, we previously constructed one largest integrated single-cell atlas IBD patient-derived tissue samples1. then used Immunai’s ImmunoDynamics EngineTM, a proprietary machine learning (ML) framework, identify transcriptional signatures inflammation...
Abstract Background Crohn’s Disease (CD) is a chronic condition that can impact any part of the gastrointestinal tract. The sustained inflammation driven by continuous influx inflammatory leukocytes into gut mucosa, which regulated through chemokine gradients and adhesion molecules, including integrins. In gut, migration cells to specific segments thought be mediated selected integrins and/or axes. CCL25/CCR9 axis has been identified as key pathway for immune cell small bowel segments, such...
Abstract Background Recently, we investigated Low-Intensity Pulsed Ultrasound (LIPUS) as a non-invasive and safe method to identify circulating biomarkers that reflect the colonic mucosal status in experimental colitis models. Here, evaluate capability of LIPUS reveal wide spectrum tissue-derived proteins metabolites potential colitis. Methods Acute was induced 10 female C57B6N mice by ad-libitum administration 2,5% dextran sodium sulfate (DSS) for 7 days. Colon-focused stimulation (38 kHz,...
Significance We discovered that SAMP1/YitFc (SAMP) mice, which develop spontaneous Crohn’s disease (CD)-like ileitis in the absence of nucleotide-binding oligomerization domain-containing 2 ( NOD2 ) genetic mutations, fail to respond muramyl dipeptide and display impaired bacterial clearance. These results support concept a dysregulated SAMP mice predisposes them chronic intestinal inflammation. believe our study provides paradigm shift by demonstrating CD-like is caused an innate immune...
Increasing evidence suggests that a deficit in innate immunity may play causative role the pathogenesis of inflammatory bowel disease. The most compelling support for this hypothesis comes from genetic association Crohn disease (CD) with carriage polymorphisms within NOD2 gene, which represent frequent defect CD. Our findings suggest SAMP1/YitFc mice, develop CD-like ileitis absence mutations, fail to respond MDP administration by displaying decreased cytokine production and impaired...
NOD2 and TLR2 recognize components of bacterial cell wall peptidoglycan direct defense against enteric pathogens. CD8+ T cells are important for immunity to such pathogens but how induce antigen specific responses is unknown. Here, we define these pattern recognition receptors (PRRs) signal in primary dendritic (DCs) influence MHC class I presentation. We show phosphorylate PI31 via TBK1 following activation DCs. interacts with Sec16A at endoplasmic reticulum exit sites (ERES), which...