There is strong evidence that some infections represent a major risk factor for the development of cancer, but how pathogens initiate this disease is still unknown and has been the focus of my research for years. During my PhD I was interested in viruses, especially the Epstein Barr Virus; this herpes virus is associated with many types of blood cancers and carcinomas. In contrast to viruses, bacteria do not transfer genetic information into the nucleus of the host cell and so it is unclear why bacterial infections are also associated with cancer. Chronic infection with Helicobacter pylori for example, is the cause of most stomach cancer cases. Investigating the direct and indirect effects of carcinogenic pathogens on the target host cells is therefore crucial for understanding how cancer begins. In every infection biology experiment you always need two ingredients: the pathogen and the host, but what is the right host to choose for the experiment? H. pylori almost exclusively infects the stomach of humans and the only host models available are mice, which poorly recapitulate the disease of humans, or human cell lines derived from gastric tumours. Although they are widely use, these cell lines are already tumours and to study the initiation of tumours using a model in which this process had already happened is paradoxical. Growing healthy cells from the stomach (or from other organs) is more difficult than growing cells from diseased ones. During my post-doc at the Max Planck Institute for Infection Biology in Berlin, I generated a model of healthy epithelial cells which faithfully reproduces in vitro most of the features of the epithelium in vivo. The most evident feature of this reconstructed epithelial layer is its formidable defence capacity against infection, which is indeed a part of the body’s innate immunity system. However, some bacteria are able to evade this defensive system and can establish a colony in the so-called infection niche. I am interested in understanding more about host-pathogen interactions in the infection niche and indeed my next challenge is to understand if the infection niche is also the place where cancer arises.
Polarised epithelial monolayers of the gastric mucosa reveal insights into mucosal homeostasis and defence against infection.
Boccellato F. et al, (2018), Gut
Helicobacter pylori Depletes Cholesterol in Gastric Glands to Prevent Interferon Gamma Signaling and Escape the Inflammatory Response.
Morey P. et al, (2018), Gastroenterology, 154, 1391 - 1404.e9
Bacteria Moving into Focus of Human Cancer.
Boccellato F. and Meyer TF., (2015), Cell Host Microbe, 17, 728 - 730
Helicobacter pylori-controlled c-Abl localization promotes cell migration and limits apoptosis.
Posselt G. et al, (2019), Cell Commun Signal, 17