- Fellowship in 2009 at the University of California, San Diego
Kepeng did his PhD study in the Hong Kong University of Science and Technology with Prof. Zhenguo Wu. His PhD study focused on the role of JAK/STAT signaling in regulating the expansion and differentiation of skeletal muscle progenitor cells. Kepeng won the Croucher Foundation Fellowship in 2009 and started his postdoctal study in Prof. Michael Karin's lab. Together with other colleagues in the lab, Kepeng discovered that colonic adenoma cells harbor defective mucin production and epithelial tight junctions. As a consequence, common microflora bacteria and their products infiltrate tumor microenviornment and trigger "tumor-elicited inflammation" that promotes the growth and progression colorectal cancer by up-regulating the production of interleukin-23 (IL-23) by tumor-associated macrophages. IL-23 in turn activates the production of IL-6 and IL-17, which signals into transformed colonic tumor cells to promote their growth. The work was published in Nature in which Kepeng is the co-first author.
Kepeng is currently working to elucidate the mechanism by which IL-17 signaling promotes the development of colorectal cancer. His research indicates that the tumor-promoting role of IL-17 in colorectal cancer can be mainly attributed to its direct signaling into transformed colonic epithelial cells. IL-17 activates ERK, p38 MAPK and NF-κB signaling pathways the promotes the survival and growth of tumor cells. Expression of IL-17 is triggered in early stage colonic tumors, and IL-17 is required for the outgrowth of aberrant crypt foci into colonic adenomas. Combined treatment with neutralizing antibody against IL-17A along with chemotherapy showed synergistic anti-tumor effect in mouse model of sporadic colorectal cancer, calling for the future use of IL-17 signaling blocking agents as adjuvant therapy in combination with conventional therapy for human colorectal cancers.