Our laboratory is interested in the chronic infection- or inflammation-induced colorectal cancer (CRC), which can cause the majority of metastatic CRC (CRC) over time without intervention. One of the most important pathogeneses of mCRC is cancer stem cell (CSC) malignancy induced by somatic mutations. Using murine and human adult stem cell- and human induced pluripotent stem cell (IPSC)-derived tumoroids, our laboratory comprehensively tests the genetic and epigenetic mechanisms of CSC malignancy during loss of anti-proinflammatory TH2 cytokine-JAKs-STAT5 signaling, further determine the targets of intervention of CSC-induced mCRC.
Research Information
Research Interests
Niche cells control stem cell responses to inflammation and malignancy. Loss of function of niche cells could lead to an exaggerate inflammation, and further various degenerative diseases. However, how gain of functions of niche cells regulates stem cells is unclear, and whether the gain of function of niche cells leads to cancer stem cell transformation or metastasis is largely unexplored. Similarly, it is also unclear by what mechanisms that a single cancer stem cell can generate metastatic niche cells or factors that in turn facilitates her invasion and migration. More importantly, knowing the differentiation of metastatic niche cells could bring an effective treatment to interfere cancer stem cell metastasis. After a decade of exploration, Dr. Han group found cytokine-STAT5 signaling is essential for maintaining epithelial integrity. Gain of functions of STAT5 activation increases stem cell activity through inducing their epithelial niche cell differentiation. Constitutively activated STAT5 promotes Lgr5 ISC migration to distant organs. Our current research aims to determine: 1) by what mechanism that constitutively activated STAT5 leads to Lgr5 cancer stem cell metastasis to distal organ. 2) develop an array of specific inhibitors targeting STAT5 aberrant activation and a steroidal herbal mimicking STAT5 inhibitors but less toxicity to test whether they can impair Lgr5 cancer stem cell metastasis.