Unravelling the role of the IL-23 axis in colorectal cancer

In animal models of both colitis-associated and sporadic (mutation-driven) cancer, as well as in human colon cancer cell lines, microbe driven IL-23 and its downstream effector IL-22 have shown to promote malignant behaviour. Importantly, recent work in the Powrie lab has identified a novel synergy between IL-22 and the key oncogenic driving mutation KRAS in human CRC.

My project will make use of primary human CRC tissue to understand the precise mechanism of synergy between IL-22 and KRAS, further asses the relevance of the IL-23 pathway and to understand the reciprocal signaling between the immune, epithelial and microbial compartments. Key targets identified and validated in the human system, may be probed in murine CRC models used in the lab, to pinpoint specific mechanisms.