A5028674889- IL-33, ST2, and ILC Pathways
- Asthma and respiratory diseases
- Eosinophilic Esophagitis
- Parasites and Host Interactions
- Macrophage Migration Inhibitory Factor
- Immune Cell Function and Interaction
- Mast cells and histamine
- Optimism, Hope, and Well-being
- Biochemical Analysis and Sensing Techniques
- Aquaculture disease management and microbiota
- Protease and Inhibitor Mechanisms
- Parasite Biology and Host Interactions
- Occupational exposure and asthma
- T-cell and B-cell Immunology
- Selenium in Biological Systems
- Genetics, Aging, and Longevity in Model Organisms
- Ubiquitin and proteasome pathways
- Helminth infection and control
- Allergic Rhinitis and Sensitization
- Antimicrobial Peptides and Activities
- Galectins and Cancer Biology
- FOXO transcription factor regulation
University of Glasgow
2018-2025
GlaxoSmithKline (Germany)
2025
Wellcome Centre for Molecular Parasitology
2018-2022
Imperial College London
2016-2017
Philipps University of Marburg
2012-2013
Max Planck Institute of Neurobiology
2010
BackgroundGenome-wide association studies have identified the ORM (yeast)-like protein isoform 3 (ORMDL3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma.ObjectiveWe sought investigate in vivo functional role of ORMDL3 disease inception.MethodsAn Ormdl3-deficient mouse was generated and generation allergic airways fungal aeroallergen Alternaria alternata determined. An adeno-associated viral vector also used reconstitute expression airway...
Helminth parasites are adept manipulators of the immune system, using multiple strategies to evade host type 2 response. In intestinal niche, epithelium is crucial for initiating immunity via tuft cells, which together with goblet cells expand dramatically in response cytokines IL-4 and IL-13. However, it not known whether helminths modulate these epithelial cell populations. vitro, small organoids, we found that excretory/secretory products (HpES) from Heligmosomoides polygyrus blocked...
Macrophage migration inhibitory factor (MIF) is a key innate immune mediator with chemokine- and cytokine-like properties in the inflammatory pathway. While its actions on macrophages are well-studied, effects other cell types less understood. Here we report that MIF required for expansion of intestinal tuft cells during infection helminth Nippostrongylus brasiliensis. MIF-deficient mice show defective responses following infection, lacking epithelial hyperplasia or upregulation goblet...
Interleukin 25 (IL-25) is a major 'alarmin' cytokine, capable of initiating and amplifying the type immune response to helminth parasites. However, its role in later effector phase clearing chronic infection remains unclear. The Heligmosomoides polygyrus establishes long-term infections susceptible C57BL/6 mice, but slowly expelled BALB/c mice from day 14 onwards. We noted that IL-25R (Il17rb)-deficient were unable expel parasites despite 2 activation comparable wild-type. then established...
Immunity to intestinal helminths is known require both innate and adaptive components of the immune system activated along Type 2 IL-4R/STAT6-dependent pathway. We have found that macrophage migration inhibitory factor (MIF) essential for development effective immunity helminth Heligmosomoides polygyrus, even following vaccination which induces sterile in wild-type mice. A chemical inhibitor MIF, 4-IPP, was similarly compromise anti-parasite immunity. Cellular analyses arm response,...
Type 2-high asthma is a chronic inflammatory disease of the airways which increasingly prevalent in countries where helminth parasite infections are rare, and characterized by T helper 2 (Th2)-dependent accumulation eosinophils lungs. Regulatory cytokines such as TGF-β can restrain reactions, dampen allergic Th2 responses, control eosinophil activation. The murine Heligmosomoides polygyrus releases mimic (Hp-TGM) that replicates biological functional properties despite bearing no structural...
Abstract Introduction Intestinal helminth parasites trigger the host immune response through epithelial sensory tuft cells, but helminth-derived molecules that may activate cells are poorly characterized. Objectives The study aimed to identify small released in vitro by two nematode parasites, infect rodents ( Nippostrongylus brasiliensis) and ruminants Haemonchus contortus ), test candidate ligands an vivo model of cell differentiation. Methods Small were analyzed hydrophilic interaction...
Abstract The pro-inflammatory mediator leukotriene B 4 (LTB ) is implicated in the pathologies of an array diseases and thus represents attractive therapeutic target. enzyme A hydrolase (LTA H) catalyses distal step LTB synthesis hence inhibitors this have been actively pursued. Despite potent LTA H entering clinical trials all failed to show efficacy. We recently identified a secondary anti-inflammatory role for degrading neutrophil chemoattractant Pro-Gly-Pro (PGP) rationalized that...
Helminth parasite infections of humans and livestock are a global health economic problem. Resistance helminths to current drug treatment is an increasing problem alternative control approaches, including vaccines, needed. Effective vaccine design requires knowledge host immune mechanisms how these stimulated. Mouse models helminth infection indicate that tuft cells, unusual type epithelial cell, may 'sense' in the small intestine trigger 2 response. Currently nothing known cells immunity...
The immunoproteasome subunit β5i has been shown to play an important role in Th1/Th17 driven models of colitis and arthritis. However, the function Th2 dependent diseases remains enigmatic. To study Th2-driven pathology, knockout (KO) control mice were tested different experimental allergic asthma. β5i-deficient showed reduced OVA/Alum- subcutaneous/OVA-induced acute asthma with decreased eosinophilia bronchoalveolar lavage (BAL), low OVA-specific IgG1 local systemic cytokines. While cells...
LMP7 subunit of the immunoproteasome has been shown to play an important role in Th1/Th17 driven models colitis and arthritis. However, nothing is known about function Th2 dependent diseases. To study pathology, experimental allergic asthma was selected as a model medically relevant disease. We used WT LMP7-/- knockout (KO) mice C57BL/6N background for induction Alum/OVA, HDM subcutaneous/OVA acute asthma. found that deficient showed reduced OVA/Alum characterized by decreased...