This laboratory has firstly established the technological platform of mouse conditional gene targeting based on the Cre-LoxP system in China, and recently set up the mouse CRISPR-Cas9 gene editing platform. The primary interest of this laboratory is to understand the mechanisms of TGF-b/Smad signaling in the maintenance of tissue homeostasis.
Our research strategies include
(1) to disrupt the cellular responses to TGF-b signals by generating various tissue specific gene knockout mice. Studies have demonstrated the causative link between the impaired TGF-b/Smad signaling and cardiovascular diseases, skeletal diseases and tumorigenesis.
(2) Using gene editing, gene targeting and transgenic technologies, to develop new genetic modeified mouse models for understanding the physiological function of TGF-β related miRNAs and lncRNAs in maintaining tissue homeostasis.
(3) In combination of genetic lineage tracing, to study cell plasticity during tissue homeostasis.;
1, Zhenhua Li, Yao Song, Lantao Liu, Ning Hou, Xiangbo An, Dawei Zhan, Ying Li, Linkang Zhou, Peng Li, Li Yu, Jiahong Xia, Youyi Zhang*, Jian Wang* and Xiao Yang*: miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation, Cell Death and Differentiation, 2017, 24(7):1205-1213.
2, Xiu-Bin Li, Guan Yang, Liang Zhu, Yu-Ling Tang, Chong Zhang, Zhenyu Ju, Xiao Yang* and Yan Teng*: Gastric Lgr5+ stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice, Cell Research, 2016, 26(7):838-849.
3, Peng Zhang, Siyuan Hou, Jicheng Chen, Jishuai Zhang, Fuyu Lin, Renjie Ju, Xuan Cheng, Xiaowei Ma, Yao Song, Youyi Zhang, Minsheng Zhu, Jie Du, Yu Lan* and Xiao Yang*: Smad4 deficiency in smooth muscle cells initiates the formation of aortic aneurysm, Circulation Research, 2016, 118(3):388-399.
4, Guan Yang*, Liang Zhu, Ning Hou, Yu Lan, Xi-Mei Wu, Bin Zhou, Yan Teng* and Xiao Yang*: Osteogenic fate of hypertrophic chondrocyte, Cell Research, 2014, 24(10):1266-1269.
5, Yu Lan*, Wenyan He, Zhuan Li, Yu Wang, Jun Wang, Siyuan Hou, Dan Liu, Jiao Gao, Weili Wang, Tao Cheng, Bing Liu* and Xiao Yang*: Endothelial Smad4 restrains transition to hematopoietic progenitors via suppressing ERK activation, Blood, 2014, 123(14):2161-2171.
6, Xueying Tian, Tianyuan Hu, Hui Zhang, Lingjuan He, Xiuzhen Huang, Qiaozhen Liu, Wei Yu, Liang He, Zhen Yang, Xiao Yang, Yan Yan, William T. Pu, Bin Zhou*: De novo formation of a compartmentalized coronary vascular population in neonatal heart, Science, 2014, 345(6192):90-94.
7, Yangmeng Wang, Hongxiu Ning, Fangli Ren, Yuanjiang Zhang, Yu Rong, Yinyin Wang, Fuqin Su, Chenguang Cai, Zhe Jin, Zhiyong Li, Xinqi Gong, Yonggong Zhai, Dianjun Wang, Baoqing Jia, Ying Qiu, Yasuhiko Tomita, Joseph J.Y. Sung, Jun Yu, David M. Irwin, Xiao Yang, Xinyuan Fu, Y. Eugene Chin and Zhijie Chang*: GdX/UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis, Molecular Cell, 2014, 53:1-14.
8, Hui Ye, Chong Zhang, Bo-Jing Wang, Xiao-Hong Tan, Wei-Ping Zhang, Yan Teng* and Xiao Yang*: Synergistic function of Kras mutation and HBx in initiation and progression of hepatocellular carcinoma in mice, Oncogene, 2014, 33(43):5133-5138.
9, Shui-Long Guo, Hui Ye, Yan Teng*, You-Liang Wang, Guan Yang, Xiu-Bin Li, Chong Zhang, Xue Yang, Zhong-Zhou Yang and Xiao Yang*: Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency, Nature Communications, 2013, 4:2544:1-11 (doi: 10.1038/ncomms3544).
10, Pengyan Xia, Shuo Wang, Ying Du, Zhenao Zhao, Lei Shi, Lei Sun, Guanling Huang, Buqing Ye, Chong Li, Zhonghua Dai, Ning Hou, Xuan Cheng, Qingyuan Sun, Lei Li, Xiao Yang*, Zusen Fan*: WASH is a negative regulator of autophagy through suppression of lysine 437 ubiquitination of Beclin 1, EMBO J, 2013, 32(20):2685-96.
11, Zhuan Li, Yu Lan, Wenyan He, Dongbo Chen, Jun Wang, Fan Zhou, Yu Wang, Huayan Sun, Xianda Chen, Chunhong Xu, Sha Li, Yakun Pang, Guangzhou Zhang, Liping Yang, Lingling Zhu, Ming Fan, Aijia Shang, Zhenyu Ju, Lingfei Luo, Yuqiang Ding, Wei Guo, Weiping Yuan, Xiao Yang* and Bing Liu*: Mouse embryonic head as a site for hematopoietic stem cell development, Cell Stem Cell, 2012, 11: 663–675.
12, Zhongwei Li, Teng Fei, Jianping Zhang, Gaoyang Zhu, Lu Wang, Danyu Lu,Xiaochun Chi, Yan Teng, Ning Hou, Xiao Yang, Hongquan Zhang, Jing-Dong J. Han and Ye-Guang Chen*: BMP4 signaling acts via dual specificity phosphatase 9 to control ERK activity in mouse embryonic stem cells, Cell Stem Cell, 2012, 10(2): 171-182.
13, Yan Zhang, Kai-Ji Fan, Qiang Sun*, Ai-Zhong Chen, Wen-Long Shen, Zhi-Hu Zhao, Xiao-Fei Zheng* and Xiao Yang*: Functional screening for miRNAs targeting Smad4 identified miR-199a as a negative regulator of TGF-β signaling pathway, Nucleic Acids Research, 2012, 40(18): 9286-9297.
14, Jian Wang, Yao Song, Yan Zhang, Han Xiao, Qiang Sun, Ning Hou, Shuilong Guo, Youliang Wang, Kaiji Fan, Dawei Zhan, Lagabaiyila Zha, Yang Cao, Zhenhua Li, Xuan Cheng, Youyi Zhang, and Xiao Yang*: Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice, Cell Research, 2012, 22(3): 516-527.
15, Fangfei Li, Yu Lan*, Youliang Wang, Jun Wang, Guan Yang, Fanwei Meng, Hua Han, Anming Meng, Yaping Wang, and Xiao Yang*: Endothelial Smad4 maintains cerebrovascular integrity by activating N-cadherin through cooperation with Notch, Developmental Cell, 2011, 20:1-12 (Preview：Ethan A. Winkler, Robert D. Bell and Berislav V. Zlokovic: Lack of Smad or Notch Leads to a Fatal Game of Brain Pericyte Hopscotch, Developmental Cell, 2011, 20:279-280).
16, Guan Yang, Qiang Sun, Yan Teng, Fangfei Li, Tujun Weng, Xiao Yang*: PTEN deficiency causes dyschondroplasia in mice by enhanced hypoxia-inducible factor-1a signaling and endoplasmic reticulum stress, Development, 2008, 135:3587-3597.
17, Qiang Sun, Yan Zhang, Guang Yang, Xiaoping Chen, Yingai Zhang, Guojun Cao, Jian Wang, Yanxun Sun, Peng Zhang, Ming Fan, Ningsheng Shao* and Xiao Yang*: Transforming growth factor-β regulated miR-24 promotes skeletal muscle differentiation, Nucleic Acids Research, 2008, 36(8):2690-2699.
18, Yan Teng, An-Na Sun, Xiao-Chen Pan, Guan Yang, Lei-Lei Yang, Ming-Rong Wang and Xiao Yang*: Synergistic function of Smad4 and PTEN in suppressing forestomach squamous cell carcinoma in the mouse, Cancer Research, 2006, 66(14):6972-6981.
19, Jian Wang, Ning Xu, Xinheng Feng, Ning Hou, JiShuai Zhang, Xuan Cheng, Youyi Zhang, and Xiao Yang*: Targeted Disruption of Smad4 in Cardiomyocytes Results in Cardiac Hypertrophy and Heart Failure, Circulation Research, 2005, 97:821-828.
20, Youliang Wang, Fang Cui, Yaxin Lu, Chuxia Deng, Xiaoling Xu, Cuiling Li, Dongping Wang, Yansong Sun, Gengxi Hu, Zhenwei Lang, Cuifen Huang, Xiao Yang*: HBsAg and HBx knocked into the p21 locus caused hepatocellular carcinoma in mice, Hepatology, 2004, 39(2):318-324.