基本信息
张雷  男  博导  中国科学院分子细胞科学卓越创新中心
电子邮件: rayzhang@sibcb.ac.cn
通信地址: 岳阳路320号,新大楼507
邮政编码: 200031

研究领域

研究方向:器官大小调控及组织稳态维持

        组织器官发育的大小最终取决于其组成细胞的数目、细胞大小及细胞间精确而复杂的排列组合,相关调控机制的异常将直接导致癌症等重大疾病的发生。Hippo信号通路是一条物种间高度保守的肿瘤抑制信号通路,是迄今被确认在调控器官发育大小、再生与重塑过程中起主导作用的信号通路。它不仅能通过调节细胞生长、增殖及凋亡来控制组织、器官的生长,还在组织稳态维持与干细胞的自我更新、分化等生命活动过程中发挥着极其重要的作用。已有研究表明,Hippo信号通路的突变或失衡可以导致包括癌症在内的多种疾病的发生。因此,阐明Hippo信号通路在器官大小调控及组织稳态维持中的作用将具有十分重要的理论与现实意义。     
        本实验室主要利用遗传学、生物化学、分子与细胞生物学等研究手段,同时结合果蝇遗传模型与小鼠疾病模型,旨在从分子、细胞和动物水平解析Hippo等信号网络在调控细胞增殖、干细胞稳态与肿瘤发生中的功能及分子机制。我们的最终目标是揭示器官发育的大小调控机制与组织稳态维持机理,并在此基础上为癌症等疾病的诊断和治疗提供可行的方法和策略。


招生信息

   
招生专业
071008-发育生物学
招生方向
发育过程的组织分化与生长调控
细胞增殖与分化
肿瘤发生,干细胞发育调控

教育背景

2001-12--2009-01   美国西南医学中心   博士后,助理讲师
1998-09--2001-06   中科院遗传与发育所   博士
1995-09--1998-06   吉林大学酶工程国家重点实验室   硕士
1991-09--1995-06   吉林大学分子生物学系,生化专业   本科

工作经历

   
工作简历
2009-01~现在, 中科院上海生科院生化与细胞研究所, 研究员
社会兼职
2015-03-01-2020-02-29,上海科技大学特聘教授, 特聘教授

专利与奖励

   
专利成果
[1] 姜海, 张雷, 徐亮, 李培学. Shank2基因的功能与用途. CN: CN109248318B, 2021-02-12.

出版信息

   
发表论文
[1] Zhang Lei. A protocol for in vivo analysis of liver tumorigenesis using sleeping beauty transposon system.. STAR Protocals. 2021, [2] Lingli He, Wentao Yu, Wenxiang Zhang, Lei Zhang. An optimized two-step chromatin immunoprecipitation protocol to quantify the associations of two separate proteins and their common target DNA. STAR Protocols. 2021, 2(2): [3] Feng, Xue, Lu, Tiantian, Li, Jinhui, Yang, Ruizeng, Hu, Liqiao, Ye, Yi, Mao, Feifei, He, Lingli, Xu, Jinjin, Wang, Zuoyun, Liu, Yingbin, Zhang, Yonglong, Ji, Hongbin, Zhao, Yun, Cheng, Shuqun, Tian, Wei, Zhang, Lei. The Tumor Suppressor Interferon Regulatory Factor 2 Binding Protein 2 Regulates Hippo Pathway in Liver Cancer by a Feedback Loop in Mice. HEPATOLOGY[J]. 2020, 71(6): 1988-2004, https://www.webofscience.com/wos/woscc/full-record/WOS:000513545500001.
[4] Gao, Jing, He, Lingli, Zhou, Lulu, Jing, Yingying, Wang, Feng, Shi, Yan, Cai, Mingjun, Sun, Jiayin, Xu, Haijiao, Jiang, Junguang, Zhang, Lei, Wang, Hongda. Mechanical force regulation of YAP by F-actin and GPCR revealed by super-resolution imaging. NANOSCALE[J]. 2020, 12(4): 2703-2714, https://www.webofscience.com/wos/woscc/full-record/WOS:000517839900048.
[5] He, Lingli, Yuan, Liang, Yu, Wentao, Sun, Yang, Jiang, Dan, Wang, Xiaodong, Feng, Xue, Wang, Zuoyun, Xu, Jinjin, Yang, Ruizeng, Zhang, Wenxiang, Feng, Hua, Chen, Hangzi, Zeng, Yi Arial, Hui, Lijian, Wu, Qiao, Zhang, Yonglong, Zhang, Lei. A Regulation Loop between YAP and NR4A1 Balances Cell Proliferation and Apoptosis. CELL REPORTS[J]. 2020, 33(3): http://dx.doi.org/10.1016/j.celrep.2020.108284.
[6] Suo, Jinlong, Feng, Xue, Li, Jiayi, Wang, Jinghui, Wang, Zuoyun, Zhang, Lei, Zou, Weiguo. VGLL4 promotes osteoblast differentiation by antagonizing TEADs-inhibited Runx2 transcription. SCIENCE ADVANCES[J]. 2020, 6(43): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608831/.
[7] Liang Xu, Peixue Li, Xue Hao, Yi Lu, Mingxian Liu, Wenqian Song, Lin Shan, Jiao Yu, Hongyu Ding, Shishuang Chen, Ailing Yang, Yi Arial Zeng, Lei Zhang, Hai Jiang. SHANK2 is a frequently amplified oncogene with evolutionarily conserved roles in regulating Hippo signaling. Protein & Cell[J]. 2020, 12(3): 174-193, https://doaj.org/article/94fd8f6207094875a9562a463d56e753.
[8] Feng, Xue, Wang, Zuoyun, Wang, Fei, Lu, Tiantian, Xu, Jinjin, Ma, Xueyan, Li, Jinhui, He, Lingli, Zhang, Wenxiang, Li, Sheng, Yang, Wenjun, Zhang, Shu, Ge, Gaoxiang, Zhao, Yun, Hu, Ping, Zhang, Lei. Dual function of VGLL4 in muscle regeneration. EMBO JOURNAL[J]. 2019, 38(17): https://www.webofscience.com/wos/woscc/full-record/WOS:000477165300001.
[9] Yu, Wei, Ma, Xueyan, Xu, Jinjin, Heumueller, Andreas Wilhelm, Fei, Zhaoliang, Feng, Xue, Wang, Xiaodong, Liu, Kuo, Li, Jinhui, Cui, Guizhong, Peng, Guangdun, Ji, Hongbin, Li, Jinsong, Jing, Naihe, Song, Hai, Lin, Zhiqiang, Zhao, Yun, Wang, Zuoyun, Zhou, Bin, Zhang, Lei. VGLL4 plays a critical role in heart valve development and homeostasis. PLOS GENETICS[J]. 2019, 15(2): https://doaj.org/article/7010330f90d545dcbf61dde5eb272596.
[10] Li, Mengjie, Hu, Xiaolong, Zhang, Shu, Ho, Margaret S, Wu, Geng, Zhang, Lei. Traffic jam regulates the function of the ovarian germline stem cell progeny differentiation niche during pre-adult stage in Drosophila. SCIENTIFIC REPORTS[J]. 2019, 9(1): http://dx.doi.org/10.1038/s41598-019-45317-6.
[11] He, Lingli, Yuan, Liang, Sun, Yang, Wang, Pingyang, Zhang, Hailin, Feng, Xue, Wang, Zuoyun, Zhang, Wenxiang, Yang, Chuanyu, Zeng, Yi Arial, Zhao, Yun, Chen, Ceshi, Zhang, Lei. Glucocorticoid Receptor Signaling Activates TEAD4 to Promote Breast Cancer Progression. CANCER RESEARCH[J]. 2019, 79(17): 4399-4411, [12] Ma, Xueyan, Li, Peixue, Chen, Peihao, Li, Jinhui, Huang, Hongling, Wang, Chao, Li, Wenjing, Ding, Jianping, Zhao, Yun, Yu, FaXing, Qi, Xiangbing, Zhang, Lei. Staurosporine targets the Hippo pathway to inhibit cell growth. JOURNAL OF MOLECULAR CELL BIOLOGYnull. 2018, 10(3): 267-269, http://lib.cqvip.com/Qikan/Article/Detail?id=675612467.
[13] Zhang Lei. The TEA domain family transcription factor TEAD4 represses murine adipogenesis by recruiting cofactors VGLL4 and CtBP2 into a transcriptional complex.. The Journal of Biological Chemistry. 2018, [14] Xiangdong Lv, Hao Chen, Shuo Zhang, Zhao Zhang, Chenyu Pan, Yuanxin Xia, Jialin Fan, Wenqing Wu, Yi Lu, Lei Zhang, Hailong Wu, Yun Zhao. Distinct functions of polycomb group proteins in regulating Ci transcription in developing Drosophila. 分子细胞生物学报:英文版. 2018, 10(5): 475-478, http://lib.cqvip.com/Qikan/Article/Detail?id=676839486.
[15] ChiaoMing Lin, JuiChou Hsu, LienChieh Cheng, YuChiao Li, WenTing Yang, Chao Wang, Jiajun Xu, Lei Zhang. Smurf Downregulates Echinoid in the Amnioserosa To Regulate Drosophila Dorsal Closure. Genetics Society of America. 2017, http://oa.las.ac.cn/oainone/service/browseall/read1?ptype=JA&workid=JA201902014133033ZK.
[16] Xu, Jiajun, Hao, Xue, Yin, MengXin, Lu, Yi, Jin, Yunyun, Xu, Jinjin, Ge, Ling, Wu, Wenqing, Ho, Margaret, Yang, Yingzi, Zhao, Yun, Zhang, Lei. Prevention of medulla neuron dedifferentiation by Nerfin-1 requires inhibition of Notch activity. DEVELOPMENT[J]. 2017, 144(8): 1510-1517, [17] Wang, Chao, Yin, MengXin, Wu, Wei, Dong, Liang, Wang, Shimin, Lu, Yi, Xu, Jinjin, Wu, Wenqing, Li, Sheng, Zhao, Yun, Zhang, Lei. Taiman acts as a coactivator of Yorkie in the Hippo pathway to promote tissue growth and intestinal regeneration. CELL DISCOVERY[J]. 2016, 2: 16006-, https://www.webofscience.com/wos/woscc/full-record/WOS:000414792900001.
[18] Zhang Lei. Importin α1 mediates Yorkie nuclear import via N-terminal non-canonical nuclear localization signal.. The Journal of Biological Chemistry. 2016, [19] Zhang Lei. Involvement of the Hippo Pathway in Regeneration and Fibrogenesis after Ischemic Acute Kidney Injury: YAP is the Key Effector.. Clinical Science. 2016, [20] Hu, Lianxin, Xu, Jiajun, Yin, MengXin, Zhang, Liguo, Lu, Yi, Wu, Wenqing, Xue, Zhaoyu, Ho, Margaret S, Gao, Guanjun, Zhao, Yun, Zhang, Lei. Ack promotes tissue growth via phosphorylation and suppression of the Hippo pathway component Expanded. CELL DISCOVERY[J]. 2016, 2: 15047-, https://www.webofscience.com/wos/woscc/full-record/WOS:000414789000001.
[21] Wang, Chao, Zhang, Wenxiang, Yin, MengXin, Hu, Lianxin, Li, Peixue, Xu, Jiajun, Huang, Hongling, Wang, Shimin, Lu, Yi, Wu, Wenqing, Ho, Margaret S, Li, Lin, Zhao, Yun, Zhang, Lei. Suppressor of Deltex mediates Pez degradation and modulates Drosophila midgut homeostasis. NATURE COMMUNICATIONS[J]. 2015, 6(1): http://www.irgrid.ac.cn/handle/1471x/968124.
[22] Dong, Liang, Li, Jinhui, Huang, Hongling, Yin, MengXin, Xu, Jinjin, Li, Peixue, Lu, Yi, Wu, Wenqing, Yang, Hang, Zhao, Yun, Zhang, Lei. Growth suppressor lingerer regulates bantam microRNA to restrict organ size. JOURNAL OF MOLECULAR CELL BIOLOGY[J]. 2015, 7(5): 415-428, https://www.webofscience.com/wos/woscc/full-record/WOS:000363201800004.
[23] Yin MengXin, Zhang Lei. Hippo signaling in epithelial stem cells. Acta Biochim Biophys Sin[J]. 2015, [24] Lei Zhang , Guest Editor. Control of growth and beyond: a special issue on Hippo signaling. 生物化学与生物物理学报:英文版. 2015, 1-1, http://lib.cqvip.com/Qikan/Article/Detail?id=664364753.
[25] Jiao, Shi, Wang, Huizhen, Shi, Zhubing, Dong, Aimei, Zhang, Wenjing, Song, Xiaomin, He, Feng, Wang, Yicui, Zhang, Zhenzhen, Wang, Wenjia, Wang, Xin, Guo, Tong, Li, Peixue, Zhao, Yun, Ji, Hongbin, Zhang, Lei, Zhou, Zhaocai. A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer. CANCER CELL[J]. 2014, 25(2): 166-180, http://dx.doi.org/10.1016/j.ccr.2014.01.010.
[26] Zhang Lei. VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEADs transcriptional complex.. Cell Research. 2014, [27] Zhang Lei. Bantam is essential for Drosophila intestinal stem cell proliferation in response to Hippo.. Developmental Biology. 2014, [28] Gao, Yijun, Zhang, Wenjing, Han, Xiangkun, Li, Fuming, Wang, Xujun, Wang, Rui, Fang, Zhaoyuan, Tong, Xinyuan, Yao, Shun, Li, Fei, Feng, Yan, Sun, Yihua, Hou, Yingyong, Yang, Zhongzhou, Guan, Kunliang, Chen, Haiquan, Zhang, Lei, Ji, Hongbin. YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression. NATURE COMMUNICATIONS[J]. 2014, 5(1): http://www.irgrid.ac.cn/handle/1471x/968298.
[29] Yunyun Jin. Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling. eLife Sciences Publications, Ltd. 2013, http://oa.las.ac.cn/oainone/service/browseall/read1?ptype=JA&workid=JA201904020614687ZK.
[30] Zhang Lei. Atrophin/Rpd3 complex represses Hedgehog signaling by interacting with Ci.. The Journal of Cell Biology. 2013, [31] Zhang Lei. Drosophila Vps36 is involved in Hh signaling by regulating Smo trafficking.. Journal of Cell Science. 2013, [32] Huang, Hongling, Wu, Wenqing, Zhang, Lei, Liu, XinYuan. Drosophila Ste-20 Family Protein Kinase, Hippo, Modulates Fat Cell Proliferation. PLOS ONE[J]. 2013, 8(4): https://doaj.org/article/e1e13b464670456ca5f295851ce15d11.
[33] Zhang, Zhao, Lv, Xiangdong, Jiang, Jin, Zhang, Lei, Zhao, Yun. Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis. CELL RESEARCHnull. 2013, 23(4): 573-576, https://www.webofscience.com/wos/woscc/full-record/WOS:000316941500015.
[34] Zhang, Meng, Dong, Liang, Shi, Zhubing, Jiao, Shi, Zhang, Zhen, Zhang, Wenqing, Liu, Guoguang, Chen, Cuicui, Feng, Miao, Hao, Qian, Wang, Wenjia, Yin, Mengxin, Zhao, Yun, Zhang, Lei, Zhou, Zhaocai. Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases. STRUCTURE[J]. 2013, 21(4): 680-688, http://dx.doi.org/10.1016/j.str.2013.02.015.
[35] Zhang, Zhao, Lv, Xiangdong, Yin, Wenchi, Zhang, Xiaoyun, Feng, Jing, Wu, Wenqing, Hui, Chichung, Zhang, Lei, Zhao, Yun. Ter94 ATPase Complex Targets K11-Linked Ubiquitinated Ci to Proteasomes for Partial Degradation. DEVELOPMENTAL CELL[J]. 2013, 25(6): 636-644, http://dx.doi.org/10.1016/j.devcel.2013.05.006.
[36] Guo, Tong, Lu, Yi, Li, Peixue, Yin, MengXin, Lv, Dekang, Zhang, Wenjing, Wang, Huizhen, Zhou, Zhaocai, Ji, Hongbin, Zhao, Yun, Zhang, Lei. A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity. CELL RESEARCH[J]. 2013, 23(10): 1201-1214, https://www.webofscience.com/wos/woscc/full-record/WOS:000325278000010.
[37] HongLing Huang, Shimin Wang, MengXin Yin, Liang Dong, Chao Wang, Wei Wu, Yi Lu, Miao Feng, Chuanyang Dai, Xiaocan Guo, Li Li, Bin Zhao, Zhaocai Zhou, Hongbin Ji, Jin Jiang, Yun Zhao, XinYuan Liu, Lei Zhang. Par-1 regulates tissue growth by influencing hippo phosphorylation status and hippo-salvador association.. PLoS Biology[J]. 2013, 11(8): https://doaj.org/article/dd46bc48791b4ce0879fd71e2a336dcc.
[38] Zhang Lei. Smoothened Oligomerization/Higher Order Clustering in Lipid Rafts is Essential for High Hh Activity Transduction. The Journal of Biological Chemistry. 2013, [39] Zhang, Yanyan, Mao, Feifei, Lu, Yi, Wu, Wenqing, Zhang, Lei, Zhao, Yun. Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus. CELL RESEARCH[J]. 2011, 21(10): 1436-1451, http://lib.cqvip.com/Qikan/Article/Detail?id=39739228.
[40] Mengxin Yin Lei Zhang. Hippo signaling: A hub of growth control, tumor suppression and pluripotency maintenance. 遗传学报. 2011, 38(10): 471-481, http://lib.cqvip.com/Qikan/Article/Detail?id=39806269.
[41] Ren, Fangfang, Zhang, Lei, Jiang, Jin. Hippo signaling regulates Yorkie nuclear localization and activity through 14-3-3 dependent and independent mechanisms. DEVELOPMENTAL BIOLOGY[J]. 2010, 337(2): 303-312, http://dx.doi.org/10.1016/j.ydbio.2009.10.046.
[42] Zhang, Lei, Yue, Tao, Jiang, Jin. Hippo signaling pathway and organ size control. FLYnull. 2009, 3(1): 68-73, https://www.webofscience.com/wos/woscc/full-record/WOS:000263028600009.
[43] Zhang Lei. The TEAD/TEF family of transcription factor Scalloped mediates nuclear responses to the Hippo pathway in organ size control.. Developmental Cell. 2008, [44] Zhang, Qing, Zhang, Lei, Wang, Bing, Ou, ChanYen, Chien, ChengTing, Jiang, Jin. A hedgehog-induced BTB protein modulates hedgehog signaling by degrading Ci/Gli transcription factor. DEVELOPMENTAL CELL[J]. 2006, 10(6): 719-729, http://dx.doi.org/10.1016/j.devcel.2006.05.004.
[45] Zhang, Lei, Jia, Jianhang, Wang, Bing, Amanai, Kazuhito, Wharton, Keith A, Jr, Jiang, Jin. Regulation of wingless signaling by the CKI family in Drosophila limb development. DEVELOPMENTAL BIOLOGY[J]. 2006, 299(1): 221-237, http://dx.doi.org/10.1016/j.ydbio.2006.07.025.
[46] Jianhang Jia, Lei Zhang, Qing Zhang, Chao Tong, Bing Wang, Fajian Hou, Kazuhito Amanai, Jin Jiang. Phosphorylation by Double-Time/CKIε and CKIα Targets Cubitus Interruptus for Slimb/β-TRCP-Mediated Proteolytic Processing. Developmental Cell. 2005, 9(6): 819-830, http://dx.doi.org/10.1016/j.devcel.2005.10.006.
[47] Hu Lianxin, Huang Hongling, Li Jinhui, Yin Meng-Xin, Lu Yi, Wu Wenqing, Zeng Rong, Jiang Jin, Zhao Yun, Zhang Lei. Drosophila Casein Kinase 2 (CK2) Promotes Warts Protein to Suppress Yorkie Protein Activity for Growth Control *. The Journal of Biological Chemistry. 289(48): 33598-33607, http://dx.doi.org/10.1074/jbc.M114.580456.
[48] Jin Yunyun, Dong Liang, Lu Yi, Wu Wenqing, Hao Qian, Zhou Zhaocai, Jiang Jin, Zhao Yun, Zhang Lei. Dimerization and Cytoplasmic Localization Regulate Hippo Kinase Signaling Activity in Organ Size Control *. The Journal of Biological Chemistry. 287(8): 5784-5796, http://dx.doi.org/10.1074/jbc.M111.310334.

科研活动

   
科研项目
( 1 ) YAP调控器官发育及稳态维持的分子机制研究, 主持, 国家级, 2016-01--2020-12
( 2 ) 细胞增殖与分化, 主持, 国家级, 2017-01--2021-12
( 3 ) 微环境信号调控肠干细胞干性的机制, 参与, 国家级, 2017-07--2021-12

指导学生

已指导学生

王超  博士研究生  071008-发育生物学  

金蕴韵  博士研究生  071008-发育生物学  

胡连鑫  博士研究生  071008-发育生物学  

董良  博士研究生  071008-发育生物学  

郭彤  博士研究生  071008-发育生物学  

李培学  博士研究生  071008-发育生物学  

王诗敏  博士研究生  071008-发育生物学  

徐佳珺  博士研究生  071008-发育生物学  

李进慧  博士研究生  071008-发育生物学  

张文翔  博士研究生  071008-发育生物学  

马雪艳  博士研究生  071008-发育生物学  

郝雪  博士研究生  071008-发育生物学  

丰雪  博士研究生  071008-发育生物学  

现指导学生

李鹏越  博士研究生  071008-发育生物学  

何伶利  博士研究生  071008-发育生物学  

杨瑞增  博士研究生  071008-发育生物学  

蒋丹  博士研究生  071008-发育生物学  

李小雨  硕士研究生  071010-生物化学与分子生物学  

孙洋  博士研究生  071008-发育生物学  

卢甜甜  博士研究生  071008-发育生物学  

佟桢竹  硕士研究生  071009-细胞生物学  

于文涛  硕士研究生  071008-发育生物学  

张颢恩  硕士研究生  071008-发育生物学