Gastrointestinal Infection and Inflammation Research Group
Research Group Head
Under the direction of Associate Professor Richard Ferrero, research conducted in this laboratory is focused on understanding how the host immune system recognises and responds to invading micro-organisms. A key area of interest is the disease-causing bacterium, Helicobacter pylori, responsible for the development of peptic ulcer disease and stomach cancer in humans. The ultimate aim of the research is to develop novel strategies to prevent the development of stomach cancer, a disease representing the third leading cause of death due to cancer world-wide.
A hallmark of H. pylori infection is the chronic inflammation (gastritis) that precedes these severe diseases. The major research theme in the group focuses on understanding how and why H. pylori induces gastritis. A broader interest of the group is to use H. pylori and other infection models to address key questions relating to the mechanisms whereby pathogens engage with the innate immune system to cause inflammation in the host.
- The use of ‘next-gen’ sequencing to identify novel H. pylori factors involved in host-pathogen interactions
- Understanding the role of cholesterol in H. pylori-mediated inflammation and disease
- Characterisation of NOD-like receptor (NLR) family members involved in innate immune signalling to H. pylori
- Investigation of the physiology of bacterial outer membrane vesicles and their role as mediators of host immune responses
The ultimate aim of these studies is to better understand the pathophysiology of the inflammatory processes that precede gastric cancer formation, a condition that causes millions of deaths worldwide each year.
NOD1 enhances IFN-g signaling in gastric epithelial cells during Helicobacter pylori infection and exacerbates disease severity. Allison CC, Ferrand J, McLeod L, Hassan M, Kaparakis-Liaskos M, Grubman A, Bhathal PS, Dev A, Sievert W, Jenkins BJ, Ferrero, R. L. J Immunol. 2013 Apr 1;190(7):3706-15.
Vitamin B6 is required for full motility and virulence in Helicobacter pylori. Grubman A, Phillips A, Thibonnier M, Kaparakis-Liaskos M, Johnson C, Thiberge JM, Radcliff FJ, Ecobichon C, Labigne A, de Reuse H, Mendz GL, Ferrero RL. MBio 2010 Aug 17;1(3). pii: e00112-10.
Helicobacter pylori induces MAPK phosphorylation and AP-1 activation via a NOD1-dependent mechanism. Allison CC, Kufer TA, Kremmer E, Kaparakis M, Ferrero RL. J Immunol. 2009 Dec 15;183(12):8099-109.
Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Kaparakis M, Turnbull L, Carneiro L, Firth S, Coleman HA, Parkington HC, Le Bourhis L, Karrar A, Viala J, Mak J, Hutton ML, Davies JK, Crack PJ, Hertzog PJ, Philpott DJ, Girardin SE, Whitchurch CB, Ferrero RL. Cell Microbiol. 2010 Mar;12(3):372-85.
Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Mémet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL. Nat Immunol. 2004 Nov;5(110:1166-74.