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Jochen Prehn is Professor of Physiology and Director of the RCSI Centre for Systems Medicine where he heads up a large research team at the interface of biomedical and translational research focusing on oncology, neuroscience, and metabolic disorders. His research includes the development of computational approaches to understand development, progression and therapy resistance in colorectal cancer and brain cancers. He recently demonstrated a direct relationship between the presence of bacteria, in particular the anaerobic bacterium Fusobacterium nucleatum, the host response to this infection, and the spread of colorectal cancer resulting in poorer outcome of patients. His research can help clinicians to identify patients at risk of poorer outcomes and make decisions on treatment options for patients whose tumours are infected with the bacterium. His team hopes that this finding will enhance diagnostics to improve the efficacy of current treatment and help further advance the use of new therapeutics for patients infected with this bacterium. This can be achieved either by interfering either with the infection itself or the host response to the infection.

1) Introduction: In Ireland, CRC accounts for 12.2% of cancers and 11.8% of cancer-related deaths, making it the second most common cancer in the country. The 5-year overall survival rate of CRC patients is 90% in the early stages, but reduced to approximately less than 10% in patients with distant metastasis. The success of chemotherapy and targeted therapies in the advanced CRC settings is limited by chemoresistance. One of the recent theories for cancer recurrence and resistance is the development of a small regenerative subpopulation of cancer cells resistant to therapies, known now as Cancer Stem Cells (CSCs). Bacterial infection is a second important contributor to tumour progression. Invasive bacterial species such as Escherichia coli NC101, Bacteroides fragilis, and Fusobacterium nucleatum (Fn) have been linked to an increased risk of CRC mediated through DNA damage and inflammation and activate Wnt signalling and EMT in tumours. Prof Prehn also researches the control of tumour progression by bacterial infection of CRCs with Fusobacterium nucleatum including spatial transcriptomics approaches and has delivered seminal research papers in this area including the first demonstration of Fn as a prognostic factor in CRC and mesenchymal subtypes of CRC. Interestingly, Fn was observed to promote CRC cells to acquire CSC characteristics, which might explain the worse disease prognosis in CRC patients with high Fn prevalence.
2) Aims and objectives:
This study aims to test the hypothesis that Fn infection triggers as CSC state in the setting of colorectal cancer. To test this hypothesis, we will use two different approaches: (a) In Vitro human colon cancer cell lines and (b) Spatial transcriptomics studies in human colon cancer tissues.
Accordingly, the main objectives of the current study are as follows:
1) To profile normal epithelial, colon cancer, and cancer stem cells exposed to Fn infection and evaluate their apoptosis sensitivity, Wnt signaling, expression of inflammatory markers, and expression of stemness markers.
2) To perform a NanoString GeoMx spatial transcriptome analysis of primary colorectal cancer tissue to correlate the expression of CSC signatures with Fn infection within the tumour, identify new cooperating gene signatures, and validate findings using an immunofluorescence multiplexing platform (Cell Dive).

A similar project is also available in the setting of glioblastoma.