杨中州实验室

杨中州，1984初中毕业后进入河南省信阳卫校学习医学检验，1987年毕业后分配至河南省驻马店市人民医院工作。1991年至1994年在北京职工医学院学习。1994年至1997年在北京大学医学部生物化学及分子生物学系攻读硕士学位。1998年6月在美国宾夕法尼亚大学做访问学者。1999年到2004年在瑞士巴塞尔大学/弗雷德里奇-米歇尔生物医学研究所攻读博士学位。2004年至2005年在瑞士弗雷德里奇-米歇尔生物医学研究所做博士后研究。2005年12月到南京大学模式动物研究所工作至今。

      我们利用组织特异性基因敲除与单细胞谱系示踪（Lineage tracing）技术，围绕心脏发育与心肌重塑两个研究方向, 选择关键发育过程和重要问题，展开系统性的研究工作。

心脏发育研究方向：我们重点关注

1.心脏祖细胞及第二心场的发育；

2.右心室及流出道的发育。

心肌重塑及再生方向: 我们利用小鼠心肌梗死（MI）、主动脉缩窄（TAC）和心肌冻伤模型，研究在心肌细胞生长、心肌再生、心功能维持以及心肌重塑等过程中起到关键调控作用的因子，探究其介导这些生物学过程发生与发展的分子机制，从而为心脏疾病的治疗提供帮助和思路。

1.    Qi Xiao, Guoxin Zhang, Huijuan Wang, Lai Chen, Shuangshuang Lu, Dejing Pan, Geng Liu* and Zhongzhou Yang*. (2017) A p53 based genetic tracing system to follow postnatal cardiomyocyte expansion in heart regeneration. Development 144: 580- 589. (Cover story/featured article, *Co-corresponding author).

2.    Junwei Nie, Mingyang Jiang, Xiaotian Zhang, Hao Tang, Hengwei Jin, Xinyi Huang, Baiyin Yuan, Chenxi Zhang, Janice Ching Lai, Yoshikuni Nagamine, Dejing Pan, Wengong Wang* and Zhongzhou Yang*. (2015) Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development. Cell Rep13,723-732.（Cover featured story/*Co-corresponding author）

3.    Fengyuan Tang, Jason Gill, Xenia Ficht, Thomas Barthlott, Hauke Cornils, Debora Schmitz-Rohmer, Debby Hynx, Dawang Zhou, Lei Zhang, Gongda Xue, Michal Grzmil, Zhongzhou Yang, Alexander Hergovich, Georg A. Hollaender, Jens V. Stein, Brian A. Hemmings, Patrick Matthias. (2015) The kinases NDR1/2 act downstream of the Hippo homologMST1 tomediate both egress of thymocytes from the thymus and lymphocyte motility. Sci. Signal. 8(397):ra100.

4.    Ji H, Zhang W, Gao Y, Li F, Tong X, Ren Y, Han X, Yao S, Long F, Yang Z, Fan H, Zhang L. (2015) YAP promotes malignant progression of Lkb1-deficient lung adenocarcinoma through downstream regulation of Survivin. Cancer Res. [Epub ahead of print]

5.    Rui Zhang, Peijuan Cao, Zhongzhou Yang, Zhenzhen Wang, Jiu-Lin Wu, Yan Chen, Yi Pan. (2015) Heparan Sulfate Biosynthesis Enzyme, Ext1, Contributes to Outflow Tract Development of Mouse Heart via Modulation of FGF Signaling. PLoS One.10(8):e0136518.

6.    Long Wang, Shanshan Cheng, Zhenyu Yin, Congyu Xu, Shuangshuang Lu, Jinxing Hou, Tingting Yu, Xiaolei Zhu, Xiaoyan Zou, Ying Peng, Yun Xu*, Zhongzhou Yang* and Guiquan Chen*. (2015) Conditional inactivation of Akt three isoforms causes tau hyperphosphorylation in the brain. Mol Neurodegener10:33.

7.    Debora Schmitz-Rohmer, Simone Probst, Zhong-Zhou Yang, Frédéric Laurent,Michael B. Stadler,Aimée Zuniga,Rolf Zeller,Debby Hynx, Brian A. Hemmings, and Alexander Hergovich. (2015) NDR Kinases Are Essential for Somitogenesis and Cardiac Looping during Mouse Embryonic Development. PLoS One. 10(8):e0136566.

8.    Wen Luo, Xia Zhao, Hengwei Jin, Lichan Tao, Jingai Zhu, Huijuan Wang, Brian A. Hemmings and Zhongzhou Yang*. (2015) Akt1 signaling coordinates BMP signaling and β-catenin activity to regulate second heart field progenitor development. Development 142, 732-742.

9.    Meixiang Yang, Dan Li, Zai Chang, Zhongzhou Yang, Zhigang Tian and Zhongjun Dong. (2015) PDK1 orchestrates early NK cell development through induction of E4BP4 expression and maintenance of IL-15 responsiveness. J. Exp. Med. 212(2):253-65.

10.  Na Xu, Shan Guan, Zhong Chen, Yang Yu, Jun Xie, Fei-Yan Pan, Ning-Wei Zhao, Li Liu, Zhong-Zhou Yang, Xiang Gao, Biao Xu and Chao-Jun Li. (2015) The alteration of protein prenylation induces cardiomyocyte hypertrophy through Rheb-mTORC1 signalling and leads to chronic heart failure. J. Pathol. 235(5):672-85.

11.  Xia Zhao, Shuangshuang Lu, Junwei Nie, Xiaoshan Hu, Wen Luo, Xiangqi Wu, Hailang Liu, Qiuting Feng, Zai Chang, Yaoqiu Liu, Yunshan Cao, Haixiang Sun, Xinli Li, Yali Hu, Zhongzhou Yang*. (2014) Phosphoinositide-Dependent Kinase 1 and mTORC2 Synergistically Maintain Postnatal Heart Growth and Heart Function in Mice. Mol. Cell. Biol. 34 (11):1966-75. (Spotlight article/cover)

12.  Baiyin Yuan, Ping Wan, Dandan Chu, Junwei Nie,Yunshan Cao, Wen Luo, Shuangshuang Lu, Jiong Chen* and Zhongzhou Yang*. (2014) A Cardiomyocyte-Specific Wdr1 Knockout Demonstrates Essential Functional Roles for Actin Disassembly during Myocardial Growth and Maintenance in Mice. Am J Pathol. 184 (7):1967-80.

13.  Qiaoli Chen, Chao Quan, Bingxian Xie, Liang Chen, Shuilian Zhou, Rachel Toth, David G. Campbell,Shuangshuang Lu, Ryutaro Shirakawa, Hisanori Horiuchi, Chaojun Li, Zhongzhou Yang, Carol MacKintosh, Hong Yu Wang, Shuai Chen. (2014) GARNL1, a major RalGAP α subunit in skeletal muscle, regulates insulin-stimulated RalA activation and GLUT4 trafficking via interaction with 14-3-3 proteins. Cell Signal 26(8):1636-48.

14.  Pei Wang, Beibei Mao, Wen Luo, Bin Wei, Wenjian Jiang, Dong Liu, Lei Song, Guangju Ji, Zhongzhou Yang,* Yong-Qiang Lai*, Zengqiang Yuan*. (2014) The alteration of Hippo/YAP signaling in the development of hypertrophic cardiomyopathy. Basic Res Cardiol.109 (5):435.

15.  Yijun Gao, Wenjing Zhang, Xiangkun Han, Fuming Li, Xujun Wang, Rui Wang, Zhaoyuan Fang, Xinyuan Tong, Shun Yao, Fei Li, Yan Feng, Yihua Sun, Yingyong Hou, Zhongzhou Yang, Kunliang Guan, Haiquan Chen, Lei Zhang & Hongbin Ji. (2014) YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression. Nat. Commun. 5:4629.

16.  Linnan Zhu, Tao Yang, Longjie Li, Lina Sun, Yuzhu Hou, Xuelian Hu, Lianjun Zhang, Hongling Tian, Qingjie Zhao, Jianxia Peng, Hongbing Zhang, Ruoyu Wang, Zhongzhou Yang, Lianfeng Zhang, Yong Zhao. (2014) TSC1 controls macrophage polarization to prevent inflammatory disease. Nat. Commun. 5:4696.

17.  Yunshan Cao, Lichan Tao, Shutong Shen, Junjie Xiao, Hang Wu, Beibei Li, Xiangqi Wu, Wen Luo, Qi Xiao, Xiaoshan Hu, Hailang Liu, Junwei Nie, Shuangshuang Lu, Baiyin Yuan, Zhonglin Han, Bo Xiao, Zhongzhou Yang*, and Xinli Li* (2013) Cardiac Ablation of Rheb1 Induces Impaired Heart Growth, Endoplasmic Reticulum-Associated Apoptosis and Heart Failure in Infant Mice. Int J Mol Sci. 14(12): 24380–24398.

18.  Hui Chen, Lianjun Zhang, Hongbing Zhang, Yi Xiao, Lijuan Shao, Hongran Li, Hui Yin, Ruoyu Wang, Guangwei Liu, Douglas Corley, Zhongzhou Yang* and Yong Zhao*.(2013) Disruption of TSC1/2 signaling complex reveals a checkpoint governing thymic CD4+CD25+Foxp3+ regulatory T-cell development in mice. FASEB J. 10：3979-3990.

19.  Xueying Tian, Tianyuan Hu, Hui Zhang, Lingjuan He,Xiuzhen Huang, Qiaozhen Liu, Wei Yu, Liang He, Zhongzhou Yang, Zhen Zhang, Tao P Zhong, Xiao Yang, Zhen Yang, Yan Yan, Antonio Baldini, Yunfu Sun,Jie Lu, Robert J Schwartz, Sylvia M Evans, Adriana C Gittenberger-de Groot, Kristy Red-Horse, and Bin Zhou. (2013) Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries. Cell Res. 23 (9): 1075-1090.

20.  Shuilong Guo, Hui Ye, Yan Teng, Youliang Wang, Guan Yang, Xiubin Li, Chong Zhang, Xue Yang, Zhongzhou Yang and Xiao Yang. (2013) Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency. Nat. Commun. 4:2544.

21.  Xue Chen, Yue Zhang, Yanhua Wang, Ding Li, Lin Zhang, Kemin Wang, Xinping Luo, Zhongzhou Yang, Yi Wu, and Junling Liu. (2013) PDK1 regulates platelet activation and arterial thrombosis. Blood 121 (18): 3718-26.

22.  Xiangqi Wu, Yunshan Cao, Junwei Nie, Hailang Liu, Shuangshuang Lu, Xiaoshan Hu, Jingai Zhu, Xia Zhao, Jiandong Chen, Xiaohu Chen, Zhongzhou Yang* and Xinli Li*. (2013) Genetic and Pharmacological Inhibition of Rheb1-mTORC1 Signaling Exerts Cardioprotection against Adverse Cardiac Remodeling in Mice. Am. J. Pathol. 182: 2005-2014.

23.  Jing-wen Yin, Yan Liang, Ji Yeon Park, Dongrui Chen, Xiao Yao, Qi Xiao, Zhen Liu, Bo Jiang, Yu Fu, Menghan Bao, Yan Huang, Yuting Liu, Jun Yan, Min-sheng Zhu, Zhongzhou Yang, Pingjin Gao, Bin Tian, Dangsheng Li and Gang Wang. (2012) Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation. Genes Dev. 26 (19): 2192-205.

24.  Qin Zhang, Xueyan He, Lai Chen, Chenxi Zhang, Xiang Gao, Zhongzhou Yang and Geng Liu. (2012) Synergistic Regulation of p53 by Mdm2 and Mdm4 is Critical in Cardiac Endocardial Cushion Morphogenesis During Heart Development. J. Pathol. 228(3):416-28.

25.  Ruomin Di, Xiangqi Wu, Zai Chang, Xia Zhao, Qiuting Feng, Shuangshuang Lu, Qing Luan, Brian A. Hemmings, Xinli Li* and Zhongzhou Yang*. (2012) S6K inhibition renders cardiac protection against myocardial infarction through PDK1 phosphorylation of Akt. Biochem. J. 441:199-207.

26.  Shuangshuang Lu, Junwei Nie, Qing Luan, Qiuting Feng, Qi Xiao, Zai Chang, Congjia Shan, Daniel Hess, Brian A. Hemmings and Zhongzhou Yang*. (2011) Phosphorylation of the Twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodeling. PLoS ONE 6: e19251.

27.  Li-Jun Ding, Gui-Jun Yan, Qiu-Yan Ge, Fei Yu, Xia Zhao, Zhen-Yu Diao, Zhi-Qun Wang, Zhong-Zhou Yang, Hai-Xiang Sun, Ya-Li Hu. (2011) FSH acts on the proliferation of type A spermatogonia via Nur77 that increases GDNF expression in the Sertoli cells. FEBS Lett. 585(15):2437-44.

28.  Ruomin Di, Qiuting Feng, Zai Chang, Qing Luan, Yangyang Zhang, Jun Huang, Xinli Li* and Zhongzhou Yang*. (2010) PDK1 plays a critical role in regulating cardiac function in mice and human. Chinese Med. J. 123:2358-2363.

29.  Zai Chang, Qin Zhang, Qiuting Feng, Jie Xu, Teng Teng, Qing Luan, Congjia Shan, Yali Hu, Brian A Hemmings, Xiang Gao and Zhongzhou Yang*. (2010) Deletion of Akt1 causes heart defects and abnormal cardiomyocyte proliferation. Dev. Biol. 347: 384-391.

30.  Fei Zhou, Zai Chang, Luqing Zhang, Young Hong, Bin Shen, Bo Wang, Fan Zhang, Guangming Lu, Denis Tvorogov, Kari Alitalo, Brian A. Hemmings, Zhongzhou Yang*, Yulong He*. (2010) Akt/ Protein Kinase B is required for lymphatic network formation, remodeling and valve development. Am. J. Path. 177: 2124-2133.

31.  Qiuting Feng, Ruomin Di, Fang Tao, Zai Chang, Shuangshuang Lu, Wenjing Fan, Congjia Shan, Xinli Li* and Zhongzhou Yang*. (2010) PDK1 regulates vascular remodeling and promotes epithelial-mesenchymal transition in cardiac development. Mol. Cell. Biol. 30: 3711-3721(Spotlight article).

32.  Francesca Buzzi, Linhua Xu, Richard A. Zuellig, Simone B. Boller, Giatgen A. Spinas, Debby Hynx, Zai Chang, Zhongzhou Yang, Brian A. Hemmings, Oliver Tschopp and Markus Niessen. (2010) Differential effects of PKB/Akt isoforms on glucose homeostasis and islet mass. Mol. Cell. Biol. 30:601-612.