Gastrointestinal Infection and Inflammation

Research > Centre for Innate Immunity and Infectious Diseases > Gastrointestinal Infection and Inflammation

h-pyloriGastrointestinal Infection and Inflammation

Research Group Head: Associate Professor Richard Ferrero

 

The research conducted in our laboratory is focused on understanding how the innate immune system recognises and responds to pathogenic bacteria. A key area of interest is the pathogen, Helicobacter pylori, responsible for the development of peptic ulcer disease and stomach cancer in humans. Half of the world’s population harbours H. pylori in their stomach and thus this infection remains a major issue for human health. Although the majority of H. pylori-infected individuals do not develop symptomatic disease, a proportion of individuals go on to develop stomach cancer. One of the aims of our research is to identify predictive biomarkers for stomach cancer, which represents the third leading cause of death due to cancer world-wide.

The critical precursor to the development of gastric cancer is chronic inflammation, or gastritis, induced by H. pylori infection. A major research focus of the laboratory is to dissect the molecular and cellular processes by which H. pylori induces this gastritis. We have demonstrated that several members of the family of innate immune signalling molecules, known as the NOD-like receptors (NLRs), have important functions in the immunopathology caused by chronic H. pylori infection. Of particular interest to our laboratory are the NLR members NOD1 and NLRC5, as well as proteins that mediate inflammasome activation.

Of broader interest to the laboratory is the study of how members of the gastrointestinal microbiota engage with the innate immune system to modulate inflammation in the host. One specific mechanism by which bacteria accomplish this is via the production of bacterial membrane vesicles. We are currently investigating the roles of these bacterial membrane vesicles in a variety of immune-mediated diseases, including cancer.

Research Projects:

  • Role of NOD1 sensing in cell survival responses and tumorigenesis
  • Regulation and functions of NLRC5 in B cell proliferation
  • Role of the inflammasome in tissue homeostasis during H. pylori infection
  • Identification of H. pylori virulence factors that regulate host immune responses
  • Immunological and other properties of bacterial membrane vesicles
  • Visualisation of membrane vesicle interactions with the immune system

 

Research Group:

Associate Professor Richard Ferrero (Research Group Head)
Dr Le Son Tran (Post-doctoral Fellow)
Amanda De Paoli (Research Assistant)
Julia Como (Research Assistant)
Natalie Bitto (PhD Student)
Michelle Butri Chonwerawong (PhD student)
Kimberley D’Costa (PhD student)
Laura Neyt (“Masters 2” student)
Darren Tran (Honours student)
Cindy Ho (UROP student)

richard-ferrero-2016-lab-group

Selected publications:

Virulence Mechanisms of H. pylori: an overview. (2016) Praszkier, J., Sutton, P., Ferrero, R. L. In: “Helicobacter pylori Research: From Bench to Bedside.” Eds. Backert & Yamaoka (Springer).  ISBN 978-4-431-55936-8

Immune modulation by bacterial outer membrane vesicles. Kaparakis-Liaskos, M., Ferrero, R. L. (2015) Nat. Rev. Immunol. 15: 376-387. doi:10.1038/nri3837

The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling. (2014) Irving AT, Mimuro H, Kufer TA, Lo C, Wheeler R, Turner LJ, Thomas BJ, Malosse C, Gantier MP, Casillas LN, Votta BJ, Bertin J, Boneca IG, Sasakawa C, Philpott DJ, Ferrero RL, Kaparakis-Liaskos M. Cell Host Microb. 15:623-35.

NOD1 enhances IFN-g signaling in gastric epithelial cells during Helicobacter pylori infection and exacerbates disease severity. (2013) 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. 190:3706-15.

Vitamin B6 is required for full motility and virulence in Helicobacter pylori. (2010) 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 1. pii: e00112-10.

Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. (2010) 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. 12:372-85.

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.