Gastrointestinal Infection and Inflammation

Research Group

Overview

Mammalian hosts defend themselves from foreign insults through the actions of the innate and adaptive arms of the immune system. The innate immune system has been conserved throughout evolution and is now recognised to play key roles in host responses to infection. Research in our laboratory is broadly directed at understanding how the innate immune system responds to disease-causing micro-organisms and how these responses lead to disease, most notably in the digestive tract.

There are three major research themes in the laboratory. The first of these concerns the stomach bacterium, Helicobacter pylori, which is responsible for one of the most common infections in humans, affecting approximately half of the world’s population. H. pylori infection is a major cause of several diseases of the digestive tract in humans, including stomach cancer and peptic ulcer disease. A hallmark of H. pylori infection is the chronic inflammation (gastritis) that precedes these severe diseases. Our research is focused on understanding how and why H. pylori induces gastritis. The ultimate aim of these studies is to better understand the pathophysiology of the inflammatory processes that precede stomach cancer, a major cause of cancer-related mortality worldwide.

A second major theme in the laboratory is the study of a family of innate immune molecules within the cytoplasm of host cells. These molecules, known as the NOD-like receptors (NLRs), act as intracellular sensors of pathogens and trigger a range of inflammatory and immune responses to infection. Dysfunctional responses by NLR family members have been associated with a range of conditions, including inflammatory bowel disease, arthritis, diabetes and various cancers. We are currently investigating the roles of NLR proteins in the development of two forms of stomach cancer resulting from chronic H. pylori infection, one affecting epithelial cells (adenocarcinoma) and the other, characterised by excessive immune cell recruitment to the stomach (mucosa-associated lymphoid tissue (MALT) lymphoma).

Lastly, our laboratory is studying the biology and immunology of membrane vesicles that are naturally released by bacteria. We have shown that these bacterial vesicles are highly efficient at entering host cells and triggering NLR signalling, thereby resulting in inflammation and cellular stress responses. Our research is directed at understanding the roles of bacterial membrane vesicles in infection.

+ Read more

Diseases we research

Areas of focus

Characterisation of the role of NLRs in cellular changes associated with stomach cancer
Regulation and biological functions of a new NLR family member that protects against MALT lymphoma
Identification of novel molecular and cellular pathways involved in the development of MALT lymphoma
Role of long non-coding RNAs in H. pylori infection
Transport by bacterial membrane vesicles of immunomodulatory molecules and genetic material into host cells and their effects on cellular functions

Research Group Head | Professor Richard Ferrero

Late diagnosis is one of the biggest issues in stomach cancer. The major focus of my research is Helicobacter pylori, responsible for one of the most common infections in humans and the causative agent of peptic ulcer disease and stomach cancer, with the goal to save lives thorough better detection and treatments.

Professor Richard Ferrero ARC Discovery Projects success

Meet the team

News from the lab

15 December 2023

H.pylori vaccine research targets stomach cancer

See more news articles about Gastrointestinal Infection and Inflammation

Student opportunities

Publication highlights

Tran LS, Ying L, D’Costa K, Wray-McCann G, Kerr G, Le L, Allison CC, Ferrand J, Chaudhry, H, Emery J, De Paoli A, Colon N, Creed S, Kaparakis-Liaskos M, Como J, Dowling JK, Johanesen PA, Kufer TA, Pedersen JS, Mansell A, Philpott DJ, Elgass K, Abud HE, Nachbur U, Croker BA, Masters SL, Ferrero RL. (2023) NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice. Nat Commun 14, 3804.
Ying L, Liu P, Ding Z, Wray-McCann G, Emery J, Colon N, Le LHM, Xu P, Yu L, Philpott DJ, Tu , Cheah DMZ, Cheng CL, Lim ST, Ong CK, Ferrero RL. (2023) Anti-CD40L therapy prevents the formation of precursor lesions to gastric B-cell MALT lymphoma in a mouse model. J Pathol 259, 402-414.
Chonwerawong M, Ferrand J, Chaudhry HM, Higgins C, Tran LS, Lim SS, Walker MM, Bhathal P, Dev A, Moore GT, Sievert W, Jenkins BJ, D’Elios MM, Philpott DJ, Kufer TA, Ferrero RL. (2020) Innate immune molecule NLRC5 protects mice from Helicobacter-induced formation of gastric lymphoid tissue. Gastroenterol 150, 169-182.
Bitto NJ, Baker PJ, Dowling JK, DePaoli A, Tran LS, Leung PL, Stacey KJ, Mansell A, Masters SL, Ferrero RL. (2018) Pseudomonas aeruginosa membrane vesicles activate the non-canonical inflammasome in human macrophages through caspase-5. Immunol Cell Biol 10, 1120-1130.
Bitto NJ, Chapman R, Pidot S, Costin A, Lo C, Choi J, D’Cruze T, Reynolds EC, Dashper SG, Turnbull L, Whitchurch CB, Stinear TP, Stacey KJ, Ferrero RL. (2017) Bacterial membrane vesicles transport their DNA cargo to the nucleus of host Sci Rep 7:7072. DOI:10.1038/s41598-017-07288-4
Kaparakis-Liaskos, M., Ferrero, R. L. (2015) Immune modulation by bacterial outer membrane vesicles. Nat Rev Immunol 15: 376-387.
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 (2014) The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling. Cell Host Microbe 15:623-635.
Allison CC, Ferrand J, McLeod L, Hassan M, Kaparakis-Liaskos M, Grubman A, Bhathal PS, Dev A, Sievert W, Jenkins BJ, Ferrero RL (2013) Nucleotide oligomerization domain 1 enhances IFN-gamma signaling in gastric epithelial cells during Helicobacter pylori infection and exacerbates disease severity. J Immunol 190:3706-3715.
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 (2010) Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Cell Microbiol 12:372-385.
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 (2010) Vitamin B6 is required for full motility and virulence in Helicobacter pylori. MBio 1:e00112-10.
Fritz JH, Ferrero RL, Philpott DJ, Girardin SE. (2006) Nod-like proteins in immunity, inflammation and disease. Nat Rev Immunol 7, 1250-1257.
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 (2004) Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 5:1166-1174.

Our research group is keen to discuss funding opportunities

Support our research

Gastrointestinal Infection and Inflammation

Overview

Diseases we research

Areas of focus

Research Group Head | Professor Richard Ferrero

Meet the team

News from the lab

Bright ideas attract major funding

Bacteria and stomach cancer: breaking the link

When stomach cancer survivor becomes expert

Stomach cancer and H.pylori – Janine’s story

Hudson Institute’s 2023 Emerging Leaders

Lymphoma treatment targets multiple diseases

High school scientists inspired by introduction to the lab

H.pylori vaccine research targets stomach cancer

Student opportunities

Publication highlights

Our research group is keen to discuss funding opportunities