Gastrointestinal Research in Inflammation & Pathology (GRIP)

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.

Group Leaders: 
Louise O'Connor
Role: 
Research Assistant
Michelle Scurr
Role: 
Research Assistant
Sharon Clohesy
Role: 
Administrator

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.

Collaborations: 

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 -)