1.Mechanisms of epithelial-mesenchymal transition (EMT) in cell fate regulation (embryonic stem cells, cancer stem cells);

2. Mechanisms of polarity establishment and maintenance in epithelial cells and related disease models (inflammatory bowel disease and other infectious diseases);

3.Drug development based on EMT and ferroptosis pathway.

1.in vivo function and molecular mechanism of SNX family.

The function and molecular mechanism of Sorting Nexins (SNXs) were systematically studied. The zebrafish model was used to study the interesting genes through the screening of temporal-spatial expression patterns and phenotypic analysis after gene knockdown. They report that SNX7 regulates cell apoptosis and liver development; SNX10 and 11 regulate V-ATPase and participate in ciliary formation; SNX16 regulates cell polarity and migration; and SNX17 regulates Notch signaling pathway and pancreatic development.

2. EMT/MET and related disease models.

How to obtain neurons, liver cells and other cells with specific functions is one of the most important topics in regenerative medicine research. Using single cell analysis and CRISPR/Cas9-mediated gene editing techniques, the process of differentiation of human embryonic stem cells into hepatocytes under completely controllable induction conditions was studied, and the function of EMT/MET in directional differentiation of hepatocytes was proved.

Using zebrafish as a model animal and gene editing technology, they constructed a variety of disease models related to the establishment/maintenance of epithelial cell polarity. They report that PIK3C3 deficiency in zebrafish results in intestinal injury and inflammation. This model provides a theoretical basis for the treatment of related human diseases and establishes a new platform for drug screening of intestinal inflammation.

Related work was published in Nature Communications, Cell Research, Hepatology and so on. The work is supported by the he National Natural Science Foundation of China, the pilot project of the Chinese Academy of Sciences, the National Major Scientific Research Program and the Science and Technology Program of Guangdong Province.

1. Shaoyang Zhao, Jianhong Xia, Xiuhua Wu,……, Duanqing Pei*, Xiaodong Shu*.Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish. Nature Communications. 2018 Jul;9(1):2639

2. Qiuhong Li, Andrew P. Hutchins, Yong Chen,……, Xiaodong Shu*, Duanqing Pei*. A sequential EMT-MET mechanism drives the differentiation of human embryonic stem cells towards hepatocytes. Nature Communications. 2017 May;8:15166

3. Liangliang Xu, Wenguang Yin,……,Duanqing Pei*,Xiaodong Shu*. An antiapoptotic role of sorting nexin 7 is required for liver development in zebrafish. Hepatology. 2012 Jun;55(6):1985-1993

4. Wenguang Yin, Dapeng Liu,……, Xiaodong Shu*, Duanqing Pei*. SNX17 regulates Notch pathway and pancreas development through the retromer-dependent recycling of Jag1. Cell Regeneration. 2012 Jun;1(1):4

5. Yanqun Chen, Bin Wu,……, Shuo Lin, Xiaodong Shu*, Duanqing Pei*. A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo. Cell Research. 2012 Feb;22(2):333-345