A5001054225- Inflammasome and immune disorders
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Gut microbiota and health
- IL-33, ST2, and ILC Pathways
- Nanoplatforms for cancer theranostics
- RNA modifications and cancer
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- Helicobacter pylori-related gastroenterology studies
- Virus-based gene therapy research
- Eosinophilic Esophagitis
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Digestive system and related health
- Nanoparticle-Based Drug Delivery
- Kawasaki Disease and Coronary Complications
- COVID-19 Clinical Research Studies
- Clostridium difficile and Clostridium perfringens research
- Exercise and Physiological Responses
- Vitamin D Research Studies
- Cancer Cells and Metastasis
- Pediatric health and respiratory diseases
- Hemoglobinopathies and Related Disorders
- RNA regulation and disease
University of Birmingham
2019-2024
Cancer Research UK
2024
University of Glasgow
2023-2024
Cancer Research UK Scotland Institute
2023
RIKEN Center for Integrative Medical Sciences
2014-2021
University of Lausanne
2011-2018
Garvan Institute of Medical Research
2009-2015
Ludwig Cancer Research
2015
St Vincent's Clinic
2011
UNSW Sydney
2011
Host-microbial interactions are central in health and disease. Monosodium urate monohydrate (MSU) crystals cause gout by activating the NLRP3 inflammasome, leading to interleukin-1β (IL-1β) production neutrophil recruitment. This study was undertaken investigate relevance of gut microbiota, acetate, metabolite-sensing receptor GPR43 regulating inflammation a murine model gout.Gout induced injection MSU into knee joints mice. Macrophages from various animals were stimulated determine...
Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result growth retardation, vitamin A deficiency, anemia poor cognitive function. Such chronicity results co-evolution between helminths their mammalian hosts; however, the molecular mechanisms by these organisms avert immune rejection not clear. We have found that natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits secretion of IL-1β vivo vitro...
The intestinal epithelium resides at the interface of gut microbiota and plays a pivotal role in shaping ecosystem.1Maslowski K.M. Clin Exp Immunol. 2019; 197: 193-204Crossref PubMed Scopus (29) Google Scholar Owing to lack tractable coculture systems, cell biological understanding host–microbe interactions remains elusive. Organoid technology allows propagation colonic under normoxia; however, conflicting oxygen demands between anaerobes makes their difficult. We established simple...
NLR family apoptosis inhibitory proteins (NAIPs) belong to both the Nod-like receptor (NLR) and inhibitor of (IAP) families. NAIPs are known form an inflammasome with NLRC4, but other in vivo functions remain unexplored. Using mice deficient for all NAIP paralogs (Naip1-6Δ/Δ), we show that key regulators colorectal tumorigenesis. Naip1-6Δ/Δ developed increased tumors, epithelial-intrinsic manner, a model colitis-associated cancer. Increased tumorigenesis, however, was not driven by...
How T cell receptor (TCR) signal strength modulates function and to what extent this is modified by immune checkpoint blockade (ICB) are key questions in immunology. Using Nr4a3-Tocky mice, we characterized early quantitative qualitative changes that occur CD4+ cells relation TCR signaling strength. We captured how dose- time-dependent programming of distinct co-inhibitory receptors rapidly recalibrates activation thresholds visualized the immediate effects ICB on re-activation. Our findings...
Disruption of cellular activities by pathogen virulence factors can trigger innate immune responses. Interferon-γ (IFN-γ)-inducible antimicrobial factors, such as the guanylate binding proteins (GBPs), promote cell-intrinsic defense attacking intracellular pathogens and inducing programmed cell death. Working in human macrophages, we discovered that GBP1 expression absence IFN-γ killed cells induced Golgi fragmentation. exposure improved macrophage survival through activity kinase PIM1. PIM1...
Abstract In lymphocytes, Nr4a gene expression is specifically regulated by antigen receptor signalling, making them ideal targets for use as distal T cell (TCR) reporters. Nr4a3-Timer of kinetics and activity (Tocky) mice are a ground-breaking tool to report TCR-driven Nr4a3 using Fluorescent Timer protein (FT). FT undergoes time-dependent shift in its emission spectrum following translation, allowing the temporal reporting transcriptional events. Our recent work suggested that Nr4a1/Nur77...
Inflammasomes are cytosolic innate immune sensors of pathogen infection and cellular damage that induce caspase-1–mediated inflammation upon activation. Although is protective, uncontrolled excessive can cause inflammatory diseases be detrimental, such as in coronavirus disease (COVID-19). However, the underlying mechanisms control inflammasome activation incompletely understood. Here we report leucine-rich repeat (LRR) protein ribonuclease inhibitor (RNH1), which shares homology with LRRs...
Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anemia and 5q– syndrome, mutations RP genes lead to a defect erythroid translation cause anemia. Little is known about the molecular mechanisms selective mRNA involvement ribosomal-associated factors this process. Ribonuclease inhibitor 1 (RNH1) ubiquitously expressed protein that binds inhibits pancreatic-type ribonucleases. Here, we report RNH1 ribosomes...
Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that binds to partners mediate responses environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with lysozyme M-Cre recombinase animals generate M-ARNT (LAR) reduced expression. Myeloid cells of LAR had altered mRNA expression and delayed wound healing. Interestingly, when rendered diabetic, difference healing between their littermate controls was no longer present,...
Abstract In CD4 + T helper cells, the active form of vitamin D 3 , 1,25‐dihydroxyvitamin (1,25D) suppresses production inflammatory cytokines, including interferon‐gamma (IFN‐γ), but mechanisms for this are not yet fully defined. innate immune response to 1,25D has been linked metabolic reprogramming. It is unclear whether similar effects on although it known that antigen stimulation these cells promotes an anabolic phenotype, characterized by high rates aerobic glycolysis support clonal...
Bacterial cancer therapy (BCT) shows great promise for treatment of solid tumors, yet basic mechanisms bacterial-induced tumor suppression remain undefined. Attenuated strains Salmonella enterica serovar Typhimurium (STm) have commonly been used in mouse models BCT xenograft and orthotopic transplant models. We aimed to better understand the epithelium–targeted by using autochthonous intestinal organoid cultures assess effectiveness consequences oral with aromatase A–deficient STm...
Abstract Bacterial cancer therapy (BCT) shows great promise for treatment of solid tumors, yet basic mechanisms bacterial-induced tumor suppression remain undefined. The intestinal epithelium is the natural route infection Salmonella and thus harbors innate immune defenses which protect against infection. Attenuated strains enterica serovar Typhimurium ( S Tm) have commonly been used in mouse models BCT, largely with use xenograft orthotopic transplant models. We aimed to better understand...
Innate immune cells sense pathogen and danger-associated molecular patterns (PAMPs DAMPs) through a range of innate pattern recognition receptors (PRRs). One type PRRs are the Nod-like (NLRs), which form inflammasomes; platform required for recruitment activation Caspase-1, in turn cleaves activates IL-1β, IL-18. Examples inflammasome forming NLRs NLRP3, NLRP1, NAIP NLRC4. We can easily identify new activators by performing following protocol.
After activation, T cells differentiate into different helper (Th) subsets, namely Th1, Th2, and Th17. These Th subsets are associated with the production of particular cytokines endowing them functions. In immunity against helminth infections Th2 cell subset plays an important role. typically produce IL-4, IL-5, IL-13, IL-9 resulting in antibody-isotype switching to IgE, eosinophilia, basophilia, mucin production, smooth muscle hyperactivity. Here we analyze development pathogen specific...