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Faculty

Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
 
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
 
Principal Investigators
 
ZHANG Lei
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Email: RayZhang@@sibcb.ac.cn

Research Areas
fruit fly; tumorigenesis; tissue differentiation; organ size control; signaling transduction; Hippo; Hedgehog (Hh), WWingless (Wg); cross-talk;CKI family; BTB protein; microRNA

Research Interests
How cell growth and organ size are regulated and how growth and patterning are coordinated is a fundamental and prevalent mechanism during animal development. It is clear that cancer always involves the inappropriate regulation of genetic pathways used during normal development. Throughout embryogenesis and tissue morphogenesis, the Hippo (Hpo), Hedgehog (Hh) and Wingless (Wg) signaling pathway regulate programmed cellular responses that are essential for normal cell growth and differentiation in invertebrate and vertebrate species. In adult organisms, they appear to be essential for stem cell self-renewal and inappropriate activation of these pathways can lead to tumor formation.
To study conserved developmental pathways, we use Drosophila as a genetic tool as initial, and we will use a combination of genetics, cell biology and biochemistry to further dissect signaling networks. 
As a novel defined tumor-suppressor pathway initially discovered in Drosophila, the Hippo (Hpo) pathway has been recognized as a conserved signaling pathway that plays a critical role in stopping organ growth. We are trying to identify additional components of the Hpo pathway exploring the upstream regulators and downstream effectors and uncovering the elusive regulation of its activation. And also, we are interested in resolving the question how it can coordinate with the other signaling.

Selected Publications

  1. Jiajun Xu, Xue Hao, Meng-Xin Yin, Yi Lu, Yunyun Jin, Jinjin Xu, Ling Ge, Wenqing Wu, Margaret Ho, Yingzi Yang, Yun Zhao, Lei Zhang*  Prevention of medulla neuron dedifferentiation by Nerfin-1 requires inhibition of Notch activity. Development  2017, 144:1510-1517
  2. Jing Gao, Lingli He, Yan Shi, Mingjun Cai, Haijiao Xu Junguang Jiang Lei Zhang*, and Hongda Wang  Cell Contact and Pressure Control of YAP Localization and Clustering Revealed by Super-resolution Imaging.  Nanoscale 2017, 9(43):16993-17003
  3. Chiao-Ming Lin, Jiajun Xu, Wen-Ting Yang, Chao Wang, Yu-Chiao Li, Lien-Chieh Cheng, Lei Zhang*, and Jui-Chou Hsu*  Smurf downregulates Echinoid in the amnioserosa to regulate Drosophila dorsal closure. Genetics, 2017, 206: 985-992
  4. Chenyu Pan, Yue Xiong, Xiangdong Lv, Yuanxin Xia, Shuo Zhang, Hao Chen, Jialin Fan, Wenqing Wu, Feng Liu, Hailong Wu, Zhaocai Zhou, Lei Zhang, Yun Zhao  UbcD1 regulates Hedgehog signaling by directly modulating Ci ubiquitination and processing  EMBO Reports 2017,18(11):1922-1934.
  5. Hsinyi Huang, Wenjing Zhang, Yafang Pan, Yijun Gao, Lei Deng, Fuming Li, Fei Li, Xueyan Ma, Shenda Hou, Jing Xu, Peixue li, Xiaoxun Li, Guohong Hu, Cheng Li, Haiquan Chen, Lei Zhang, and Hongbin Ji  YAP suppresses lung squamous cell carcinoma progression via deregulation of the DNp63-GPX2 axis and ROS accumulation. Cancer Research, 2017, 77(21): 5769-5781
  6. Shuo Zhang, Chenyu Pan, Xiangdong Lv, Wei Wu, Hao Chen, Wenqing Wu, Hailong Wu, Lei Zhang, Yun Zhao  Repression of Abd-B by Polycomb is critical for cell identity maintenance in adult Drosophila testis. Scientific Report 2017, 7:5101
  7. Shi Jiao, Chuanchuan Li, Qian Hao, Haofei Miao, Lei Zhang, Lin Li, Zhaocai Zhou  VGLL4 targets a TCF4CTEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer. Nature communications  2017, 8:14058
  8. Shimin Wang, Yi Lu, Meng-Xin Yin, Chao Wang, Wei Wu, Jinhui Li, Wenqing Wu, Ling Ge, Lianxin Hu, Yun Zhao, Lei Zhang* Importin α1 mediates Yorkie nuclear import via N-terminal non-canonical nuclear localization signal. The Journal of Biological Chemistry 2016,291(15):7926-37
  9. Chao Wang, Meng-Xin Yin, Wei Wu, Liang Dong, Shimin Wang, Yi Lu, Jinjin Xu, Wenqing Wu, Sheng Li, and Yun Zhao Lei Zhang* Taiman acts as a co-activator of Yorkie in the Hippo pathway to promote tissue growth and intestinal regeneration. Cell Discovery 2016,2,16006
  10. Lianxin Hu, Jiajun Xu, Meng-Xin Yin, Liguo Zhang, Yi Lu, Wenqing Wu, Zhaoyu Xu, Margaret S. Ho, Guanjun Gao, Yun Zhao, Lei Zhang*  Ack promotes tissue growth via phosphorylation and suppression of the Hippo pathway component Expanded. Cell Discovery 2016, 2, 15047
  11. Peng Zhang, Shuting Wang, Sai Wang, Jing Qiao, Lei zhang, Zhe Zhang Zhengjun Chen  Dual Function of Partitioning-defective 3 in the Regulation of YAP Phosphorylation and Activation. Cell Discovery, 2016,2, 16021
  12. Lin Fu, Hailong Wu, Steven Y. Cheng, Daming Gao, Lei Zhang, Yun Zhao Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammal. eLife 2016, 5:e15690
  13. Xiangdong Lv, Hao Chen, Bo Yang, Xiaofeng Yang, Yuanxin Xia, Chenyu Pan, Lin Fu, Shuo Zhang, Hui Han, Zhaocai Zhou, Lei zhang, Zhijun Han, Gang Wei, Min Wu, Lin LI, Yun Zhao A Positive Role for Polycomb in Transcriptional Regulation via H4K20me1. Cell Research 2016, 26:529-542
  14. Xiangdong Lv, Chenyu Pan, Zhao Zhang, Yuanxin Xia, Hao Chen, Shuo Zhang,Tong Guo, Hui Han, Haiyun Song, Lei Zhang, and Yun Zhao  SUMO Regulates Somatic Cyst Stem Cells Maintenance and Directly TargetsHedgehog Pathway in Adult Drosophila Testis. Development  2016, 143(10):1655-62
  15. Jing Xu, Pei-xue Li, Jun Wu, Yi-jun Gao, Meng-xin Yin, Ye Lin, Ming Yang, Dong-ping Chen, Hai-peng Sun, Zeng-bo Liu, Xiang-chen Gu, Hong-ling Huang, Li-li Fu, Hui-min Hu, Liang-liang He, Wen-qing Wu, Zhao-liang Fei, Hong-bin Ji, Lei Zhang*, Chang-Lin Mei* Involvement of the Hippo Pathway in Regeneration and Fibrogenesis after Ischemic Acute Kidney Injury: YAP is the Key Effector.  Clinical Science 2016,130:349-363
  16. Hui Han, Jialin Fan, Yue Xiong, Yi Lu, Wenqing Wu, Lei Zhang, and Yun Zhao Chi and dLMO function antagonistically on Notch signaling through directly regulation of fng transcription. Scientific Reports 2016618937
  17. Fangfang Jiang, Falong Lu, Peixue Li, Wei Liu, Lu Zhao, Qifu Wang, Xiaofeng Cao, Lei Zhang, and Yong Q. Zhang Drosophila homolog of FMRP maintains genome integrity by interacting with Piwi. Journal of Genetics and Genomics 2016, 43:11-24
  18. Chao Wang, Wenxiang Zhang, Meng-Xin Yin, Lianxin Hu, Peixue Li, Jiajun Xu, Hongling Huang, Shimin Wang, Yi Lu, Wenqing Wu, Margaret S. Ho, Lin Li, Yun Zhao, Lei Zhang*  Suppressor of Deltex mediates Pez degradation and modulates Drosophila midgut homeostasis.  Nature Communications 2015, 6:6607
  19. Liang Dong, Jinhui Li, Hongling Huang, Meng-Xin Yin, Jinjin Xu, Peixue Li, Yi Lu, Wenqing Wu, Hang Yang, Yun Zhao, Lei Zhang* Growth Suppressor Lingerer Regulates bantam microRNA to Restrict Organ Size. Journal of Molecular Cell Biology 2015 7(5):415-428
  20. Mengxin Yin and Lei Zhang*  Hippo signaling in epithelial stem cells. Acta Biochimica et Biophysica Sinica 2015, 47(1):39-45 (invited review)
  21. Lei Zhang*  Control of growth and beyond: a special issue on Hippo signaling. Acta Biochimica et Biophysica Sinica 2015, 47(1):1 (Editorial)
  22. Wenjing Zhang, Yijun Gao, Fuming Li, Xinyuan Tong ,Yan Ren, Xiangkun Han, Shun Yao, Fei Long, Zhongzhou Yang, Hengyu Fan, Lei Zhang, Hongbin Ji  YAP promotes malignant progression of Lkb1-deficient lung adenocarcinoma through downstream regulation of Survivin. Cancer Research 2015,75(21):4450-7
  23. Shuying Shen, Xiaocan Guo, Huan Yan, Yi Lu, Xinyan Ji, Li Li, Tingbo Liang, Dawang Zhou, Xin-Hua Feng, Jonathan Zhao, Jindan Yu, Xing-Guo Gong, Lei zhangBin Zhao  A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis. Cell Research 2015,25(9):997-1012
  24. Chunying Liu, Yue Xiong, Jing Feng, Lei Zhang, Yun Zhao  Sqh is involved in the regulation of Ci stability in Hh signaling pathway. Journal of Molecular Cell Biology 2015, 7(6),584-587
  25. Hui Han, Chenyu Pan, Chunying Liu, Xiangdong Lv, Xiaofeng Yang, Yue Xiong, Yi Lu,Wenqing Wu, Junhai Han, Zhaocai Zhou, Hai Jiang, Lei Zhang, Yun Zhao  GutCneuron interaction via Hh signaling regulates intestinal progenitor cell differentiation in Drosophila. Cell Discovery 2015, 1:15006
  26. Ye Zhu, Dong Li, Yadong Wang, Chunli Pei, Song Liu, Lei Zhang, Zengqiang Yuan, Peng Zhang  Brahma regulates the Hippo pathway activity through forming complex with Yki-Sd and regulating the transcription of Crumbs. Cellular Signalling 2015, 27: 606-613
  27. Lianxin Hu, Hongling Huang, Jinhui Li, Meng-Xin Yin, Yi Lu, Wenqing Wu, Rong Zeng, Jin Jiang, Yun Zhao and Lei Zhang* Drosophila Casein Kinase 2 (CK2) Promotes Warts Protein to Suppress Yorkie Protein Activity for Growth Control. The Journal of Biological Chemistry 2014, 289:33598-33607
  28. 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*  YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression. Nature Communications 2014, 5:4629
  29. Shi Jiao, Huizhen Wang, Zhubing Shi, Aimei Dong, Wenjing Zhang, Xiaomin Song, Feng He, Yicui Wang, Zhenzhen Zhang, Wenjia Wang, Xin Wang, Tong Guo, Peixue Li, Yun Zhao, Hongbin Ji*, Lei Zhang*, Zhaocai Zhou*. A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer. Cancer Cell 2014, 25: 166-180
  30. Hongling Huang, Jinhui Li, Lianxin Hu, Ling Ge, Hongbin Ji, Yun Zhao*, Lei Zhang*  Bantam is essential for Drosophila intestinal stem cell proliferation in response to Hippo. Developmental Biology 2014, 385:211-219
  31. Wenjing Zhang, Yijun Gao, Peixue Li, Zhubing Shi, Tong Guo, Fei Li, XiangKun Han, Yan Feng, Chao Zheng, Zuoyun Wang, Fuming Li, Haiquan Chen, Zhaocai Zhou*, Lei Zhang* and Hongbin Ji*  VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEADs transcriptional complex. Cell Research  2014, 24: 331-343
  32. Feifei Mao, Xiaofeng Yang, Lin Fu, Xiangdong Lv, Zhao Zhang, Wenqing Wu, Siqi Yang, Zhaocai Zhou, Lei Zhang, Yun Zhao  Kto-Skd complex can regulate ptc expression by interacting with Ci in Hedgehog signaling pathway. The Journal of Biological Chemistry 2014 289 (32): 22333-41
  33. Xiangkun Han, Fuming Li, Zhaoyuan Fang, Yijun Gao, Fei Li, Rong Fang, Shun Yao, Yihua Sun, Li Li, Wenjing Zhang, Huimin Ma, Qian Xiao, Gaoxiang Ge, Jing Fang, Hongda Wang, Lei Zhang, Kwok-kin Wong, Haiquan Chen, Yingyong Hou, Hongbin Ji. Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma. Nature Communications 2014, 5:3261
  34. Yunyun Jin, Jinjin Xu, Meng-Xin Yin, Yi Lu, Lianxin Hu, Peixue Li, Peng Zhang, Zengqiang Yuan, Margaret S. Ho, Hongbin Ji, Yun Zhao*, Lei Zhang*  Brahma is essential for Drosophila Intestinal Stem Cell proliferation and regulated by Hippo signaling. eLife 2013 2: e00999
  35. 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*, Xin-Yuan Liu* and Lei Zhang*  Par-1 regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biology 2013,11(4) e1001620 (Press released by PLoS Biology)
  36. Tong Guo, Yi Lu, Peixue Li, Meng-Xin Yin, Dekang Lv, Wenjing Zhang, Huizhen Wang, Zhaocai Zhou, Hongbin Ji, Yun Zhao*, Lei Zhang*  A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity. Cell Research 201323:1201-1214
  37. Zhao Zhang, Jing Feng, Chenyu Pan, Xiangdong Lv, Wenqing Wu, Zhaocai Zhou,Feng Liu, Lei Zhang* and Yun Zhao*   Atrophin/Rpd3 complex represses Hedgehog signaling by interacting with Ci. The Journal of Cell Biology 2013, 203:575-583
  38. Zhao Zhang,  Xiangdong Lv,  Wen-chi Yin,  Xiaoyun Zhang, Jing Feng, Wenqing Wu, Chi-chung Hui, Lei Zhang* and Yun Zhao*  Ter94 ATPase Complex Targets K11-Linked Ubiquitinated Ci to Proteasomes for Partial Degradation. Developmental Cell 2013, 25: 636-644
  39. Xiaofeng Yang, Feifei Mao, Xiangdong Lv, Zhao Zhang, Lin Fu, Yi Lu, Wenqing Wu, Zhaocai Zhou, Lei Zhang*, and Yun Zhao*. Drosophila Vps36 is involved in Hh signaling by regulating Smo trafficking. Journal of Cell Science. 2013126:4230-4238
  40. Hongling Huang, Wenqing Wu, Lei Zhang* and Xin-Yuan Liu* Drosophila Ste-20 family protein kinase, Hippo, modulates Fat cell proliferation.  PLoS One  2013, 8: e61740
  41. Dawei Shi, Xiangdong Lv, Zhao Zhang, Xiaofeng Yang, Zhaocai Zhou, Lei Zhang*, and Yun Zhao* Smoothened Oligomerization/Higher Order Clustering in Lipid Rafts is Essential for High Hh Activity Transduction    The Journal of Biological Chemistry  2013,  288(18): 12605-12614
  42. Meng Zhang, Liang Dong, Zhubing Shi, Shi Jiao, Zhen Zhang, Wenqing Zhang, Guoguang Liu, Cuicui Chen, Miao Feng, Qian Hao, Wenjia Wang, Mengxin Yin, Yun Zhao, Lei Zhang* and Zhaocai Zhou*. Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases. Structure 2013, 21:680-688
  43. Zhao Zhang, Xiangdong Lv, Jin Jiang, Lei Zhang*, Yun Zhao*. Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis. Cell Research 2013 23(4): 573-576
  44. Zhubing Shi, Shi Jiao, Zhen Zhang, Miao Ma, Zhao Zhang, Cuicui Chen, Ke Wang, Huizhen Wang, Wenjia Wang, Lei Zhang, Yun Zhao, and Zhaocai Zhou. Structure of the MST4 in Complex with MO25 Provides Insights into Its Activation Mechanism. Structure 2013, 21: 449-461
  45. Yunyun Jin, Liang Dong, Yi Lu, Wenqing Wu, Qian Hao, Zhaocai zhou, Jin Jiang, Yun Zhao*  and Lei Zhang*. Dimerization and cytoplasmic localization regulate Hippo kinase signaling activity in organ size control. The Journal of Biological Chemistry 2012, 287: 5784-5796
  46. Mengxin Yin and Lei Zhang*. Hippo signaling, a hub of growth control, tumor suppression and pluripotency maintenance. Journal of Genetics and Genomics 2011, 38: 471-481 (invited review)
  47. Yanyan Zhang, Feifei Mao, Yi Lu, Wenqing Wu, Lei Zhang* and Yun Zhao*. Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus. Cell Research 2011, 21: 1436-1451
  48. Fangfang Ren, Lei Zhang, Jin Jiang. Hippo signaling regulates Yorkie nuclear localization and activity through 14-3-3 dependent and independent mechanisms. Developmental Biology  2010, 337, 303-312
  49. Lei Zhang, Tao Yue and Jin Jiang. Hippo signaling pathway and organ size control. Fly 2009, 3(1), 1-6 (invited review).
  50. Lei Zhang, Fangfang Ren, Qing Zhang, Yongbin Chen, Bing Wang, and Jin Jiang. The TEAD/TEF family of transcription factor Scalloped mediates nuclear responses to the Hippo pathway in organ size control.  Developmental Cell  200814377-387
  51. Lei Zhang, Jianhang Jia, Bing Wang, Kazuhito Amanai, Keith A. Wharton Jr, Jin Jiang. Regulation of wingless signaling by the CKI family in Drosophila limb development. Developmental Biology 2006, 299: 221-237
  52. Qing Zhang#, Lei Zhang#, Bing Wang, Chan-Yen Oh, Cheng-Ting Chien, ang Jin Jiang. A Hedgehog-Induced BTB Protein Modulates Hedgehog Signaling by Degrading Ci/Gli Transcription Factor. Developmental Cell 2006, 10719-729 (* Equally contributed to this work)
  53. Jianhang Jia#, Lei Zhang#, Qing Zhang# Chao Tong, Bing Wang, Fajian Hou, Kazuhito Amanai and Jin Jiang. Phosphorylation by Double-time/CKIε and CKIα targets Cubitus interruptus for Slimb/β-TRCP mediated proteolytic processing. Developmental cell  2005, 9: 819-830  (* Equally contributed to this work)
  54. Zhipan Yang, Lei zhang, Fengqiu Diao, Meijuan Huang, Naihu Wu Sucrose regulates elongation of Carrot somatic embryo radicles as a signal molecule.Plant Molecular Biology 200454441-459
  55. HuiXin.Lin, Lei Zhang, Zhipan Yang, Meijuan Huang, Naihu Wu* Molecular Characterization of Poly(A)-binding Protein from Daucus carota.DNA sequencing 2004, 14(2): 147-153
  56. Yiming Liu, Fengqiu Diao, Lei Zhang, Meijuan Huang, Naihu Wu*  Cloning and function analysis of DcLEA1 , a new number of LEA gene family Progress in Natural Science,14(5) 20-26 (2004)
  57. Huixin Lin, Lei Zhang, Zhipan Yang, Meijuan Huang, Naihu Wu*  Isolation and Functional Identification of DcPAB from Daucus carota  Chinese Journal of Biochemistry and Molecular biology 2004, 20 (3)319-324 (in Chinese, English abstract)
  58. Zhipan Yang, lei Zhang, Fengqiu, Meijuan Huang, Naihu Wu*  Cloning and expression of DnaJ homolog in Carrot somatic embryo. Progress in Natural Science 2003,13(5) 350-356
  59. Lei Zhang, Zhipan Yang, Yiming Liu, Meijuan Huang, Naihu Wu* Analysis of gene expression in carrot somatic embryonic development by differential screening of a cDNA library.Progress in Natural Science 2002,12(3) 261-265  (in Chinese)
  60. Lei Zhang, Fengqiu Diao, Zhipan Yang, Meijuan Huang, Naihu Wu* Isolation and characterization of a new member of sucrose carrier cDNA from carrot by functional expression in yeast. Chinese Science Bulletin 2001,46(14) 1190-1195  (in Chinese)
  61. Fengqiu Diao, Lei Zhang, Meijuan Huang, Naihu Wu*  Isolation of development-related genes in somatic embryo radicle of carrot (Daucus carota L.) using modified cDNA RDA.     Science in China. 2000, 43(1) 47-56
  62. 俯唱 嫖跡 歎海爽  自來楓鱒彬楓弌砿壅伏俐鹸距陣議冩梢序婢  嶄鯖楓壜押墫崗  Chin J Nephrol. 2013, 29: 631-634 忝峰
  63. 藍階嫖猟茖呶知蠖嫖跡*  Hippo佚催距陣惚哮嶄界糧蓑略隔議字崙冩梢 嶄忽聾飲伏麗僥僥烏糟囃念冽Chinese Journal of Cell Biology 2015 375 599-603 忝峰
  64. 嫖跡坎奐膿巓寄履孕遠  Hippo佚催宥揃再郊寄弌嚥怏岶糧蓑距陣匂 凖勧 Hereditas (Beijing) 2017, 39(7): 535-536  (Hippo廨侵念冱)
  65. 柾慕忽*伶弊芦*嫖跡* Hippo佚催宥揃壓惚哮凖勧僥冩梢嶄議窟嶝訐婢  凖勧 Hereditas (Beijing) 2017, 39(7): 537-545 忝峰
  66. 綱垓嫖跡噫窟佛 Hippo佚催宥揃壓界祇糧蓑、壅伏式逢延狛殻嶄議恬喘式字崙 凖勧 Hereditas (Beijing) 2017, 39(7): 588-596 忝峰
     
 

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