Chang Liao, PhD, Postdoctoral Fellow University of California, San Francisco Colorectal cancers represent a significant public health issue. Despite screening, available treatments, and increased awareness of lifestyle-related risk factors, the lifetime risk of colorectal cancer remains high in the US. There is an urgent need to identify new targets for therapeutics. Thymic stromal lymphopoietin (TSLP) is a key alarmin cytokine expressed at barrier tissues with a broad impact on immune homeostasis. The regulatory role of TSLP in inflammatory bowel diseases has been suggested to be associated with Th2 inflammation, although the mechanisms remain elusive. Group 2 innate lymphoid cells (ILC2s) are major downstream targets of TSLP. How TSLP and ILC2s contribute to intestinal homeostasis and pathology in colitis and cancers is less well understood. Recent studies suggest a role for TSLP in tumorigenesis and metastasis in several cancers. Despite a role for TSLP in colitis and recognition of colitis as a predisposing condition for colorectal cancer, the impact of TSLP on intestinal tumorigenesis remains poorly investigated. Dr. Liao proposes to use novel and precise reagents to characterize the role of TSLP and ILC2s in promoting colorectal malignancy. She hypothesizes that TSLP is a trigger for ILC2-mediated intestinal remodeling that when dysregulated can promote epithelial hyperplasia and contribute to the development of colorectal malignancy. Dr. Liao’s study will provide novel insights on TSLP cell sources in the intestine, the mechanisms of TSLP-ILC2 signaling in mediating intestinal epithelial remodeling in homeostasis and colorectal cancers, and therapeutic potential of targeting the TSLP-ILC2 signaling axis in colorectal cancer treatments. Projects and Grants Immune regulatory role of TSLP in colorectal cancer development University of California, San Francisco | All Cancers | 2022 | Richard Locksley, M.D.
