A5019815080- Gastroesophageal reflux and treatments
- Eosinophilic Esophagitis
- Gastrointestinal motility and disorders
- Helicobacter pylori-related gastroenterology studies
- Diet and metabolism studies
- Ion Channels and Receptors
- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- Macrophage Migration Inhibitory Factor
- Chemokine receptors and signaling
- Esophageal Cancer Research and Treatment
- Diabetes Treatment and Management
- Gut microbiota and health
- Galectins and Cancer Biology
- Connective tissue disorders research
- Tissue Engineering and Regenerative Medicine
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Cell Adhesion Molecules Research
- Proteoglycans and glycosaminoglycans research
- Respiratory and Cough-Related Research
- Systemic Lupus Erythematosus Research
- Clostridium difficile and Clostridium perfringens research
- Cancer-related molecular mechanisms research
- Peroxisome Proliferator-Activated Receptors
Queen Mary University of London
2015-2024
The University of Melbourne
2024
Biotechnology and Biological Sciences Research Council
2022
The University of Queensland
2007-2008
<h3>Objective</h3> Inhibition of food intake and glucose homeostasis are both promoted when nutrients stimulate enteroendocrine cells (EEC) to release gut hormones. Several specific nutrient receptors may be located on EEC that respond dietary sugars, amino acids fatty acids. Bypass surgery for obesity type II diabetes works by shunting the distal gut, where it increases activation mediator release, but cellular mechanisms largely unknown. We determined which expressed in regions mouse...
Background and aims As the importance of gut–brain interactions increases, understanding how specific gut microbes interact with enteric nervous system (ENS), which is first point neuronal exposure becomes critical. Our aim was to understand dominant human bacterium Bacteroides thetaiotaomicron (Bt) regulates anatomical functional characteristics ENS.Methods Neuronal cell populations, as well enteroendocrine cells, were assessed in proximal colonic sections using fluorescent...
Little is known about the mucosal phenotype of proximal human esophagus. There evidence to suggest that esophagus more sensitive chemical and mechanical stimulation compared with distal. This may have physiological relevance (e.g., in prevention aspiration gastroesophageal refluxate), but also pathological reflux perception or dysphagia). Reasons for this increased sensitivity are unclear include impairment barrier integrity changes sensory innervation. We assessed afferent nerve...
TRPV1 is a nociceptive, Ca2+-selective ion channel involved in the development of several painful conditions. Sensitization responses by cAMP-dependent PKA crucially contributes to inflammatory hyperalgesia. However, pathways potentiation remain largely unknown. Using HEK cells stably expressing and μ opioid receptor, we demonstrated that treatment with adenylate cyclase activator forskolin significantly increased multimeric species. Pretreatment receptor agonist morphine reversed this...
Objective The development of effective visceral analgesics free deleterious gut-specific side effects is a priority. We aimed to develop reproducible methodology study nociception in human tissue that could aid future target identification and drug evaluation. Design Electrophysiological (single unit) responses afferents mechanical (von Frey hair (VFH) stretch) chemical (bradykinin ATP) stimuli were examined. Thus, serosal (putative nociceptors) used investigate the effect tegaserod,...
Key points Tenascin‐X (TNX) is an extracellular matrix glycoprotein with anti‐adhesive properties in skin and joints. Here we report the novel finding that TNX expressed human mouse gut tissue where it exclusive to specific subpopulations of neurones. Our studies TNX‐deficient mice show impaired defecation neural control distal colonic motility can be rescued a 5‐HT 4 receptor agonist. However, secretion unchanged. They are also susceptible internal rectal intussusception. Colonic afferent...
Objective Colonic enteroendocrine cells (EECs) store and release potent anorectic hormones that are key regulators of satiety. EECs express multiple nutrient sensing receptors, particularly for medium-chain fatty acids (MCFAs): GPR84 FFAR4. Here we show a non-surgical approach with targeted colonic delivery MCFA, which induces EEC neuronal activation leading to effects. Design A randomised, double-blind, placebo-controlled, cross-over study was performed in obese adults given combined FFAR4...
<h3>Background</h3> Conditions characterised by chronic visceral pain represent a significant healthcare burden with limited treatment options. While animal models have provided insights into potential mechanisms of nociception and identified candidate drug targets, these not translated successful treatments in humans. <h3>Objective</h3> To develop an vitro afferent nerve preparation using surgically excised freshly isolated human colon vermiform appendix-mesentery tissues. <h3>Methods</h3>...
BackgroundChronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1–KV7.5) voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pathways. Here, we use combination immunohistochemistry, gut-nerve electrophysiological recordings both mouse human tissues, single-cell qualitative real-time polymerase chain reaction gut-projecting neurons, to investigate contribution...
Background: Nutrient-sensing receptors located on enteroendocrine (EEC) cells modulate appetite via detection of luminal contents. Colonic ‘tasting’ contents may influence changes to observed in obesity and after weight loss induced by bariatric surgery. We assessed the effects gastric bypass-induced expression nutrient-sensing G-protein coupled (GPCRs), EEC enterochromaffin (EC) mucosal innervation. Methods: qPCR immunohistochemistry were used study colonic tissue from (a) chow-fed/lean,...
We demonstrate for the first time that increased pain perception in patients with nonerosive reflux disease likely results from expression of acid-sensitive channels on superficial mucosal afferents and esophageal epithelial cells, raising potential topical therapy.
Abstract Monocytes are mononuclear phagocytes that can differentiate to a variety of cell fates under the influence their microenvironment and hardwired commitment. We found inhibition TRPM8 in human blood CD14+ monocytes during critical 3-h window at beginning differentiation into macrophages led enhanced survival LPS-driven TNFα production after 24 h. antagonism also promoted derived from intestinal mucosa. Macrophages had been for 6 days blockade impaired phagocytic capacity were...
Introduction Heartburn pathogenesis in GERD remains incompletely understood. We aimed to identify differences the immune cell signature and sensory mucosal markers between reflux phenotypes healthy asymptomatic subjects. Methods Thirty-seven patients with heartburn symptoms were phenotyped endoscopically objective studies into erosive disease (ERD) (N=10), nonerosive (NERD) (N=9), functional (FH) Barrett’s esophagus (BO) (N=9). Bulk mRNA-sequencing(RNA-seq) was conducted on RNA extracted...
Key points Tenascin X (TNX) functions in the extracellular matrix of skin and joints where it maintains correct intercellular connections tissue architecture TNX is associated exclusively with vagal‐afferent endings some myenteric neurones mouse human stomach, respectively. TNX‐deficient mice have accelerated gastric emptying hypersensitivity vagal mechanoreceptors that can be normalized by an inhibitor sensitivity. Cultured nodose ganglion showed no changes response to capsaicin,...
Abstract The perineuronal net (PNN) is a well‐described highly specialized extracellular matrix structure found in the central nervous system. Thus far, no reports of its presence or connection to pathological processes have been described peripheral Our study demonstrates PNN spinal afferent innervation distal colon mice and characterizes structural morphological alterations induced an ulcerative colitis (UC) model. C57Bl/6 were given 3% dextran sulfate sodium (DSS) induce acute chronic UC....
Abstract Background Chronic and recurring pain is a characteristic symptom in irritable bowel syndrome (IBS). Altered signaling between immune cells sensory neurons within the gut may promote generation of symptoms. As transient receptor potential melastatin 8 (TRPM8) agonists, such as L‐menthol peppermint oil, have shown to attenuate IBS symptoms, we began investigating molecular mechanisms. Methods Colonic biopsy tissues were collected from patients with controls, two separate cohorts....
Abstract Gastro-oesophageal reflux disease (GORD) is a chronic condition characterised by visceral pain in the distal oesophagus. The current first-line treatment for GORD proton pump inhibitors (PPIs), however, PPIs are ineffective large cohort of patients and long-term use may have adverse effects. Emerging evidence suggests that nerve fibre number location likely to play interrelated roles nociception oesophagus patients. Simultaneously, alterations cells oesophageal mucosa, namely...