The Gastrointestinal Research in Inflammation and Pathology (GRIP) group investigates how chronic gut inflammation leads to disease and how targeted intervention in inflammatory signalling pathways can ameliorate pathological outcomes.
Chronic inflammation is behind many childhood diseases including gut cancers, inflammatory bowel disease, asthma, and eosinophilic oesophagitis. Understanding the causes of this chronic inflammation and designing interventions to reduce or block ongoing inflammatory processes will help alleviate a wide range of diseases. The group’s work is at the cutting edge of this research, particularly with respect to gut inflammation.
Cytokine signaling in gastroesophageal cancer
This project focuses on how certain cytokines promote cancer of the gastroesophageal junction, the implications for Barretts oesophagitis and the consequential development of oesophageal carcinoma.
The role of IL-33 in driving Th2-biased pathological outcomes in the oesophagus and stomach
IL-33 is an alarmin and inflammatory cytokine which signals and activates the immune system in response to damage or infection. GRIP researchers are investigating the role that IL-33 plays in promoting Th2-biased pathological outcomes in eosinophilic oesophagitis and bacterial gastropathy in children, and in model systems.
Epithelial-specific regulators of the innate immune response to bacterial infection
This research focuses on two families of regulatory proteins, trefoil factors and gastrokines, expressed predominantly by gut epithelial cells. The project aims to understand how trefoil factors and cytokines regulate inflammation and how this could be harnessed to prevent inflammatory disease progression.
Endogenous regulation of inflammation in colitic
GRIP is investigating the role for the cytokine IL-11 in regulating the immune response in colitis. In particular, the group is examining the capacity of IL-11 induced activation of the transcription factor STAT3 to stimulate a class of regulatory cells known as myeloid derived suppressor cells (MDSC). The ultimate goal is to understand the role for MDSC in regulating inflammation in the colon.
IL-11 can dysregulate gastric homeostasis
GRIP was the first to fully describe a role for IL-11 in the maintenance of the normal gastric mucosa as well as in gastric inflammation or gastropathy. The group also linked elevated IL-11 expression with progressive H. pylori gastric disease including gastric cancer. These results have now been confirmed by a number of other groups. GRIP is continuing these studies with a particular focus on how IL-11 can specifically modulate the gastric inflammatory response.
- Altered gp130 signalling ameliorates experimental colitis via myeloid cell-specific STAT3 activation and myeloid-derived suppressor cells. 2016
- Combining an epithelial repair factor and anti-fibrotic with a corticosteroid offers optimal treatment for allergic airways disease. 2016
- Loss of gastrokine-2 drives premalignant gastric inflammation and tumor progression. 2016
- Nontuberculous Mycobacterial Disease in Children - Epidemiology, Diagnosis & Management at a Tertiary Center. 2016
- Short bowel syndrome (SBS)-associated alterations within the gut-liver axis evolve early and persist long-term in the piglet model of short bowel syndrome. 2016
- Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis. 2015
- Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. 2015
- Multipotent caudal neural progenitors derived from human pluripotent stem cells that give rise to lineages of the central and peripheral nervous system. 2015
- Perinatal inflammation: a common factor in the early origins of cardiovascular disease? 2015
- Reprogramming of monocytes by GM-CSF contributes to regulatory immune functions during intestinal inflammation. 2015
- TFF2 deficiency exacerbates weight loss and alters immune cell and cytokine profiles in DSS colitis, and this cannot be rescued by wild-type bone marrow. 2015
- Diagnostic utility of faecal biomarkers in patients with irritable bowel syndrome. 2014
- Granulocyte macrophage colony-stimulating factor and the intestinal innate immune cell homeostasis in Crohn's disease. 2014
- IL-1RT1 signaling antagonizes IL-11 induced STAT3 dependent cardiac and antral stomach tumor development through myeloid cell enrichment. 2014
- Inhibition of the JAK2/STAT3 pathway reduces gastric cancer growth in vitro and in vivo. 2014
- Lineage-specific RUNX3 hypomethylation marks the preneoplastic immune component of gastric cancer. 2014
- Linking immunity, epigenetics, and cancer in inflammatory bowel disease. 2014
- Significance of hydrogen breath tests in children with suspected carbohydrate malabsorption. 2014
- Fecal S100A12: identifying intestinal distress in very-low-birth-weight infants. 2013
- Gastrokines: stomach-specific proteins with putative homeostatic and tumor suppressor roles. 2013
- Granulocyte Macrophage Colony-Stimulating Factor Auto-Antibodies and Disease Relapse in Inflammatory Bowel Disease. 2013
- Improving relapse prediction in inflammatory bowel disease by neutrophil-derived S100A12. 2013
- Increased immunoexpression of trefoil factors in salivary gland tumors. 2013
- Mechanistic Insights into the Contribution of Epithelial Damage to Airway Remodeling: Novel Therapeutic Targets for Asthma. 2013
- Peripheral monocyte functions and activation in patients with quiescent Crohn's disease. 2013
- S100A12 and hBD2 Correlate with the Composition of the Fecal Microflora in ELBW Infants and Expansion of E. coli Is Associated with NEC. 2013
- Validation of relapse risk biomarkers for routine use in patients with juvenile idiopathic arthritis. 2013
- A novel TFF2 splice variant (Delta EX2TFF2) correlates with longer overall survival time in cholangiocarcinoma 2012
- Helicobacter pylori CagA Triggers Expression of the Bactericidal Lectin REG3 gamma via Gastric STAT3 Activation 2012
- Targeting STAT3 in gastric cancer 2012
- Alternative splicing isoforms of TFF2 (?EX2TFF2) mRNA in cholangiocarcinoma 2011
- Identification of SLC26A4 Mutations in Patients with Hearing Loss and Enlarged Vestibular Aqueduct Using High-Resolution Melting Curve Analysis 2011
- IL-11 is a parietal cell cytokine that induces atrophic gastritis 2011
- Inactivation of IL11 Signaling Causes Craniosynostosis, Delayed Tooth Eruption, and Supernumerary Teeth 2011
- Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma 2011
- Random mutagenesis of the mouse genome: a strategy for discovering gene function and the molecular basis of disease 2011
- Trefoil Factors in Saliva and Gingival Tissues of Patients With Chronic Periodontitis 2011
- Trefoil factors: Tumor progression markers and mitogens via EGFR/MAPK activation in cholangiocarcinoma 2011
Professor Jim Fox, MIT, USA; Professor Tim Wang, Columbia University, USA. Mechanisms by which H. pylori and its induced cytokines epigenetically silence gastric tumour suppressor and regulatory genes (2010-)
Professor Khay Guan Yeoh & Dr. David Ong, Department of Gastroenterology & Hepatology, National University Hospital (NUS), Singapore. New biomarkers in gastric neoplasia (2012- )
Professor Waldermar Priebe, MD Anderson Cancer Centre, Houston, USA. Development and testing of improved STAT3 inhibitors (2006-)
Dr. Toshi Minamoto, Cancer Research Institute, Kanazawa University, Japan. Human biobanking repository for gastric cancer research (2010-)
Associate Professor Reginald Lord, St. Vincents Hospital, Sydney. Cancer of the gastric cardia and the cardiac mucosa as a precursor for oesophageal pathology (2014- )
Dr. Alexandra Corbett and Professor Jim McCluskey, PDI, University of Melbourne. MAIT cells and chronic H.pylori infection (2014 -)
Associate Professor Phil Sutton, MCRI. Endogenous gut epithelial regulators of the innate immune system (2012-)
Dr. Ralf Heine and Professor Katie Allen, MCRI. Cytokine drive in eosinophilic oesophagitis (2012 -)