ECCO Grant Study Synopsis: Ana Montalban-Arques
Ana Montalban-Arques, ECCO Grant Awardee
The role of PTPN23 in intestinal inflammation and colitis-associated cancer
© Ana Montalban-Arques
Aim of research
Inflammatory Bowel Disease with colonic involvement predisposes patients to develop colitis-associated cancer (CAC) due to chronic inflammation. Protein tyrosine phosphatases (PTP) play a critical role in the regulation of signalling cascades involved in IBD and oncogenesis. Particularly PTPN23 deletion has recently been associated with epithelial cancers. However, a role of PTPN23 in IBD and CAC/CRC has not yet been investigated. Based on previous data, our hypothesis is that PTPN23 controls intestinal epithelial cell (IEC) homeostasis and proliferation. The overarching aim of our project is to investigate the role of PTPN23 in intestinal homeostasis and inflammation.
Methodology/experiments that will be used
For this purpose, we will first analyse the expression of PTPN23 in human IBD and CAC/CRC tissue and
examine whether it correlates with disease course or stage. Further, we will investigate how loss of PTPN23 in IECs affects barrier function, apoptosis, proliferation, immune response and intestinal microbiota in a mouse model lacking PTPN23 specifically in IECs. Finally, in a mouse model of CAC, we will study how loss of PTPN23 promotes colitis and CRC development in vivo.
Anticipated main impact
The experiments will define the role of PTPN23 in the pathogenesis of IBD and CAC in vivo. Our data will help to characterise a novel player in the pathogenesis of IBD and CAC and may contribute to the identification of a novel therapeutic target for the treatment of both diseases.
Months 1–3: Determination of functional PTPN23 in intestinal tissue from patients with CRC, patients with IBD and healthy controls. Correlation of PTPN23 expression with inflammation and tumour stage.
Months 1–8: Analysis of the relevance of PTPN23 for intestinal homeostasis, barrier function, apoptosis, proliferation and immune response.
Months 6–12: Investigation of the relevance of PTPN23 for the development of CAC in mouse models.