Ricerc@Sapienza

Colorectal cancer (CRC) is the second most common cancer in women and third in men, and, overall, the fourth cause of tumor death world-wide. The etiology of CRC is heterogeneous depending on both genetic and environmental factors, including intestinal bowel disease (IBD). Innate lymphoid cells (ILCs) are critical regulators of the intestinal homeostasis, and provide protection from pathogens by quickly triggering inflammation. Moreover, recent findings link the function of ILCs with the progression or clearance of CRC.
Given the importance of innate lymphoid cells (ILCs) in the regulation of intestinal functions, I hypothesized that targeting pro-inflammatory modules in NCR+ ILCs will limit inflammation and tumor formation, in colitis-induced CRC.
The research program I propose will employ a broad approach combining different mouse models of acute colitis and CRC, with cutting-edge next-generation sequencing technologies. Moreover, established and novel mouse models targeting Stat4 in the innate compartment and NCR+ ILCs will be employed to identify the role of this transcription factor in regulation of colon inflammation.
My research plan aims at 1) evaluating the effect of the selective Stat4 deletion in NCR+ ILCs during CRC pathogenesis using established and novel mouse strains; and 2) study the contribution of cell proliferation to the accumulation of NK cells in the inflamed tissues and tumors.
Building upon our unpublished data, I expect that targeting the STAT4-dependent inflammatory modules in NCR+ ILCs will impact the effector programs limiting inflammation and tumor formation, in colitis-induced CRC. This study will provide novel insights into pathways involved in CRC pathogenesis. Moreover, a better understanding of the mechanisms underlying regulation of intestinal NK cell and ILC functions, in settings of inflammation and cancer, will provide the framework to design novel preventive and therapeutic strategies against CRC development and progression.