The Role of Bacterial Infections in Human Carcinogenesis
The human mucosa is the major crossing point for molecular interaction between our body and the environment. This is where most pathogens initiate their infections and where our defense system is challenged to rapidly counteract any approaching assaults. Repeated or persistent onslaughts of this kind, however, tend to cause permanent damage to our epithelium and, not surprisingly, the mucosal epithelium is the site most prone to carcinogenesis, a consequence of enhanced mutagenesis, inflammation and cell proliferation. Several clear links have been noted between chronic bacterial infections and carcinogenesis; however, the underlying mechanisms of this relationship are still sparsely understood. Exploring these mechanisms promises to pave the way towards better prevention and treatment of the disease.
Our research applies sophisticated approaches to illuminate the relationship between infection and cancer:
The gastric pathogen Helicobacter pylori is the paradigm of a cancer-inducing bacterium. Understanding the mechanisms behind this link will help to define the principles of an infection-cancer connection. We are also investigating the mechanisms behind the suggested carcinogenic effects of several other bacterial species, including Chlamydia trachomatis, Salmonella typhi and Escherichia coli.
Human organoids and mucosoids
The use of human primary cell culture models is crucial for authentic investigations of
cancer emergence. We have pioneered the use of innovative organoid and mucosoid
models, providing invaluable tools for modelling infection processes and their
consequences in untransformed cells.
Functional genomics of cancer initiation
Breakthrough technologies, such as RNA interference and CRISPR/Cas9, are extensively used in our work to decipher beneficial and potentially deleterious gene functions and genetic defects.
Origin of cancer initiating cells
While our understanding of cancer evolution and progression has greatly improved in
recent years, the initiation of carcinogenesis is a much more elusive phenomenon. We
are developing sophisticated genetic lineage tracing tools to help illuminate the very
earliest events in cancer initiation as a result of infection and the various stages
Analysing human cancer progression
In collaboration with clinical centres we analyse cancerous and precancerous human tissue samples to guide us in our understanding of the various stages of cancer initiation and progression as well as the role of infectious agents in these processes.
Signatures of infection in the cancer genome
Unlike oncogenic viruses, bacteria do not leave genetic material in the genome of host
cells. It is therefore much more difficult to prove that some bacterial infections can
promote the emergence of cancer – often many years later. Nonetheless,
epidemiology suggests that these bacteria-cancer relationships exist. Identifying genetic
signatures that bacterial pathogens might leave behind in human cells might therefore
provide genuine proof the causality between infections and cancer emergence and
facilitate our understanding of the molecular mechanisms responsible.
We are using the most advanced tools of molecular biology, genetics and genomics
in order to identify such signatures.