Regulation of intestinal regeneration and cancer by the lysine methyltransferase Set7

Intestinal epithelial cells (IECs) form a protective covering over the small and large intestine. They are the primary interface between the body and the external environment, and  are constantly turning over, completely renewing every three to five days. This impressive turnover requires tight control of stem and progenitor cell production and variation, which is mediated by various cell signalling pathways including the Hippo and Wnt pathways.

In his study, Dr. Oudoffaims to dissect the exact role the protein-coding gene Set7 has in control of the Hippo and Wnt pathways in IEC homeostasis, regeneration, and cancer. The role of Set7 will be examined in two different in vivo intestinal regeneration models.

Systematically, his team will perform in vitro biochemical and cell biological assays to define the mechanism through which Set7 acts to regulate Hippo and Wnt pathways. In preliminary studies, Dr. Oudhoff identified that Set7 negatively regulates IEC production and turnover by regulating the Hippo pathway in vivo. Based on these results, his team tested whether the increased IEC proliferation would cause tumor development. Crossing mice lacking Set7 to mice that tended to spontaneously develop intestinal tumors, Dr. Oudhoff’s team hypothesized that mice having overactive Setd7 and overactive Wnt would develop more adenomas (benign tumors) or would develop them faster.

Ultimately, these studies will attempt to provide novel therapeutic targets to treat intestinal cancers.