许执恒
职称：研究员

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联系电话：86- (O)

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研究方向：信号转导与疾病的病理生理机制


许执恒，博士，研究员，博士生导师
　　1989年获上海第二军医大学医学学士系学位，1999年获美国新泽西Rutgers大学博士学位。1999-2005在美国哥伦比亚大学神经生物学和精神病中心做博士后及高级研究助理。先后获得美国NIH的 Ruth L. Kirschstein National Research Service Award (2002-03)及Rutgers大学Bush Fellowship (1997-1999)和Waksman Fellowship (1993-1997)，2005年中国科学院“****”入选者，2007年国家****科学基金获得者。

主要研究方向
　　利用本课题组在信号转导通路方面的优势，结合基因操作小鼠模式动物，进行神经和疾病病理机制研究，争取在阐明TGF信号通路在大脑发育中的作用，以及重要疾病发生的分子机制方面有所突破。相关研究将有助于我们为疾病的预防和治疗提供理论依据，同时为个体正常发育的分子机理提供新见解。
主要研究内容：
　　1) 用分子、生化和细胞生物学为手段研究不同蛋白激酶复合体在信号传导通路中的作用与调节机制，进一步揭示JNK信号传导通路在神经发育和肿瘤及神经退行性疾病病理过程中的意义。
　　2) 建立和利用基因操作小鼠模型研究小颅畸形、精神分裂症、自闭症和神经退行性疾病的发病机制。
　　Email: zhxu@genetics.ac.cn
　　Tel:



POSH/JIP复合体参与细胞凋亡






POSH/JIP复合体参与神经分化与迁移



RECENT PUBLICATIONS (* Corresponding author)
1.Xu D, Li C, Qin CF, Xu Z*(2019) Update on the Animal Models and Underlying Mechanisms for ZIKV-Induced Microcephaly. Annu. Rev. Virol. doi.org/10.1146/annurev-virology-092818-015740
2.Nielsen-Saines K, Xu Z, Cheng G, Moreira (2019) Early childhood neurodevelopmental outcomes in a prospective cohort of in utero ZIKV-1 exposed children from Rio de Janeir, Nat Med (in press).
3.Li H, Saucedo-Cuevas L, Yuan L, Ross D, Johansen A, Sands D, Stanley V, Guemez-Gamboa A, Gregor A, Evans T, Chen S, Tan L, Molina H, Sheets N, Shiryaev SA, Terskikh AV, Gladfelter AS, Shresta S, Xu Z, Gleeson JG. (2019).Zika Virus Protease Cleavage of Host Protein Septin-2 Mediates Mitotic Defects in Neural Progenitors. Neuron. 20;101(6):1089-1098.e4. doi: 10.1016/j.neuron.2019.01.010.
4.Chang YF, Jiang YS, et al., Xu Z* (2019) Dissecting of the Gene Networks Affected by Zika Virus Infection in a Mouse Microcephaly Model. Genomics Proteomics & Bioinformatics (accepted).
5.Wang XT et al., Xu Z*, Shen Y* (2019) MEA6 deficiency impairs cerebellar development and motor performance by tethering protein trafficking. Frontiers in Cellular Neuroscience (in press)
6.Xu YP, Qiu Y, Zhang B, Chen G, Chen Q, Wang M, Mo F, Xu J, Wu J, Zhang RR, Cheng ML, Zhang NN, Lyu B, Zhu WL, Wu MH, Ye Q, Zhang D, Man JH, Li XF, Cui J, Xu Z, Hu B, Zhou X, Qin CF. (2019) Zika virus infection induces RNAi-mediated antiviral immunity in human neural progenitors and brain organoids. Cell Res. 2019 Apr;29(4):265-273. doi: 10.1038/s41422-019-0152-9.
7.Wang S. et al., Xu Z*. (2018). Sh3rf2 haploinsufficiency leads to unilateral neuronal development deficits and autistic-like behaviors in mice. Cell Reports DOI:10.1016/j.celrep.2018.11.044
8.Zhang et al., Xu Z* (2018) cTAGE5/MEA6 Controls Brain Development through Regulation of Neuronal Trafficking of Cellular Components. PNAS doi/10.1073/pnas.
(Direct Submission Plus)
9.Xu D., Zhu Y., and Xu Z*. (2018) MEKK3 Coordinates with FBW7 to Regulate WDR62 Stability and Neurogenesis. PLoS Biology 19;16(12):e**. doi: 10.1371/journal.pbio.**
10. Li C et al., Xu Z*, Zhang L*. (2018). A single injection of human neutralizing antibody protects against Zika virus infection and microcephaly in the developing fetuses. Cell Reports DOI: 10.1016/j.celrep.2018.04.005
11. Li C et al., Xu Z*. (2018). Disruption of Glial Cell Development by Zika Virus Contributes to Severe Microcephalic Newborn Mice. Cell Discovery DOI: 10.1038/s41421-018-0042-1.
12. Zhu X, Li C, Afridi SK, Zu S, Xu JW, Quanquin N, Yang H, Cheng G^*, Xu Z*. (2018). E90 subunit vaccine protects mice from Zika virus infection and microcephaly. Acta Neuropathol Commun. 2018 Aug 10;6(1):77. doi: 10.1186/s40478-018-0572-7. (IF: 5.4)
13. Zhou Y... Xu Z*, Chen ZJ*, Gao F*. (2018). Wdr62 is involved in meiotic initiation via activating JNK signaling and associated with POI in humans. PLoS Genet. 13;14(8):e**. doi: 10.1371/journal.pgen.**.
14. Zhang H...Xu Z, Sun T. (2018). Upregulation of MicroRNA miR-9 Is Associated with Microcephaly and Zika Virus Infection in Mice. Mol Neurobiol. doi: 10.1007/s12035-018-1358-4.
15. Shohayeb B, Lim NR, Ho U, Xu Z, Dottori M, Quinn L, Ng DCH. (2018). The Role of WD40-Repeat Protein 62 (MCPH2) in Brain Growth: Diverse Molecular and Cellular Mechanisms Required for Cortical Development. Mol Neurobiol. 55(7):5409-5424. doi: 10.1007/s12035-017-0778-x.
16. Ling Y,.. Xu Z*, Qin CF^*. (2017). A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. SCIENCE eaam7120, DOI: 10.1126/science.aam7120 (Highlighted by Nature, Science, PNAS et al., Covered by >100 media, including New York Times, Reuters, The Washington Post, Los Angeles Times, USA Today, NBC News, NPR, The Scientist, etc.)
17. Fan et al., Xu Z* (2017) Mea6 Deletion in Pancreatic β Cells Impairs Proinsulin Trafficking and Insulin Biogenesis in Mice. J Cell Biology DOI: 10.1083/jcb.
18. Wang S., Hong S... Xu Z*. (2017) Transfer of Convalescent Serum to Pregnant Mice Prevents Zika Virus Infection and Microcephaly in Offspring. Cell Research doi:10.1038/cr.2016.144
19. Deng et al., Xu Z*, Qin CF^*. Intranasal infection and contact transmission of Zika virus in guinea pigs. Nat. Commun. doi:10.1038/s41467-017-01923-4
20. Li C, Deng Y-Q, Wang S...Xu Z^*, Qin C^*, Cheng G^*. (2017) 25-Hydroxycholesterol protects host against ZIKV infection and its associated microcephaly. Immunity 46(3):446-456. doi: 10.1016/j.immuni.2017.02.012
21. Oh Y et al., Xu Z^*, Jin P^*, Song H., Ming G-L^*, Lee G^*. (2017) Zika virus directly infects human peripheral neurons and induces cell death. Nature Neuroscience 20(9):1209-1212. doi: 10.1038/nn.4612. (*Senior author)
22. Zhang et al., Xu Z* (2017) American Strain of Zika Virus Causes More Severe Microcephaly than an Old Asian Strain in neonatal Mice. EBioMedicine doi: 10.1016/j.ebiom.2017.10.019.
23. Li C, Zhu X,. .. Xu Z*, Cheng G^*. (2017) Chloroquine, a FDA-approved Drug, Prevents ZIKV Infection and its Associated Congenital Microcephaly in Mice. EBioMedicine doi:10.1016/j.ebiom.2017.09.034
24. Yoon KJ, et al., Xu Z, Qian J^*, Zhu H^*, Song H^*, Ming G-L^*. (2017) NS2A protein encoded by Zika virus disrupts mammalian cortical neurogenesis. Cell Stem Cell 21(3):349-358.e6. doi: 10.1016/j.stem.2017.07.014.
25. Wang S....Z Xu and Z Fan. (2017) Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation. CELL 171(1):201-216.e18. doi: 10.1016/j.cell.2017.07.027.
26. Xu D., Zhu Y., and Xu Z*. (2017) Efficient genetic manipulation in the developing brain of tree shrew using in utero electroporation and virus infection. J Genetics and Genomics doi: 10.1016/j.jgg.2017.09.007
27. Li C, Xu D, .. Qin C*, Xu Z*. (2016) Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice. Cell Stem Cell doi:10.1016/j.stem.2016.04.017 (Highlighted by Science, Nature Reviews Neurobiology, Nature Reviews Microbiology; Trends in Molecular Medicine, etc. Covered by >100 media, including BBC, Reuters, Los Angeles Times, USA Today, NBC News, Fox News, The Scientist, etc. ‘Best of Cell Stem Cell 2016’)
28. Zhang HS…. Xu Z*. (2016) Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice. Nat. Commun. doi: 10.1038/ncomms11773.
29. Wang Y, Liu L,.. Xu Z*. (2016) Mea6 controls VLDL transport through the coordinated regulation of COPII assembly. Cell Research doi:10.1038/cr.2016.75
30. Zhang F. Yu JW, Yang T. Xu D,.Xia YH., Xu Z*. (2016) A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development. J Biol Chem pii: jbc.M116.716811. (Cover story, “Paper of the week” with editorial comments and highlight for the student)
31. Zhang L, Zhang F,... Xu Z*. (2016) The B cell receptor BR3 modulates cellular branching via Rac1 during neuronal migration. J Mol Cell Biol. pii: mjw034
32. Xu D. and Xu Z*. (2016) Driving WDR62 to the Pole. Cell Cycle DOI:10.1080/**. 2016.**
33. Shao XM. et al., (2016) Numb Regulates Vesicular Docking for Homotypic Fusion of Early Endosomes via Membrane Recruitment of Mon1b. Cell Research doi: 10.1038/cr.2016.34
34. Liu B…Xu Z., ZhengYF. (2016) MAZ mediates the cross-talk between CT-1 and NOTCH1 signaling during gliogenesis. Sci Reports 6:21534. doi: 10.1038/srep21534
35. Liu K, Lei R, Li Q, Wang XX, Wu Q, An P, Zhang J, Zhu M, Xu Z, Hong Y, Wang F, Shen Y, Li H, Li H. (2016) Transferrin Receptor Controls AMPA Receptor Trafficking Efficiency and Synaptic Plasticity. Sci Rep. 6:21019. doi: 10.1038/srep21019
36. Li P… Xu Z*, and Zhu Z*. (2015) Epigenetic silencing of microRNA-149 in cancer associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment Cell Research 25(5):588-603
37. Lim NR, Yeap YY, Zhao TT, Yip YY, Wong SC, Xu D, Ang CS, Xu Z, Bogoyevitch MA, Ng DC. (2015) Opposing roles for JNK and Aurora A in regulating WD40-Repeat Protein 62 association with spindle microtubules. J Cell Sci. 128:527-540
38. Zhang F. Xu D,. Sun YM., Xu Z*. (2014) Epigenetic regulation of Atrophin1 by lysine-specific demethylase is required for cortical progenitor maintenance. Nat. Commun, 5:5815. doi: 10.1038/ncomms6815
39. Xu D. Zhang F, Wang Y, Sun Y, Xu Z*. (2014) Microcephaly Associated Protein WDR62 Regulates Neurogenesis through JNK1 in the developmental cortex. Cell Reports 6(1):104-16
40. Yu J, Zhang F, Zhang Y, Fan M and Xu Z* (2014) TAK1 is activated by TGF-β signaling and controls axonal growth during brain development. J Mol Cell Biol. 6(4):349-51.
41. Yao M, Wang Y, Zhang P, Chen H, Xu Z, Jiao J, Yuan Z. (2014) BMP2-SMAD Signaling Represses the Proliferation of Embryonic Neural Stem Cells through YAP. J Neuroscience 34(36):12039-48
42. Zhu Y, Wang C, Yu M, and Xu Z*. (2013) ULK1 and JNK are Involved in Mitophagy Incurred by LRRK2 G2019S Expression. Protein Cell 4(9): 711-21.
43. Shi W, Chen Y, Gan G, Ren J, Wang Q, Xu Z, Xie X, and Zhang Y. (2013) Brain tumor regulates neuromuscular synapse growth and endocytosis in Drosophila by suppressing Mad expression. J Neuroscience 24;33(30):12352-63.
44. Xiong Y, Zhao K, Wu J, Xu Z, Jin S, Zhang YQ. (2013) HDAC6 mutations rescue human tau-induced microtubule defects in Drosophila. PNAS 19;110(12):4604-9.
45. Yang T., Sun YM…Xu Z* (2012) POSH Localizes Activated Rac1 to Control the Formation of Cytoplasmic Dilation of the Leading Process and Neuronal Migration. Cell Reports 2(3):640-51 (Article).
46. Wilhelm M, Kukekov NV, Schmit TL, Biagas KV, Sproul AA, Gire S, Maes ME, Xu Z, Greene LA.（2012）Sh3rf2/POSHER protein promotes cell survival by ring-mediated proteasomal degradation of the c-Jun N-terminal kinase scaffold POSH (Plenty of SH3s) protein. J Biol Chem. 287(3):2247-56.
47. J Niu, M Yu and Z Xu*. (2012) Leucine-Rich Repeat Kinase 2 (LRRK2) Disturbs Mitochondrial Dynamics via Dynamin-Like Protein (DLP1). J NeuroChem 122(3):650-8.
48. J Cui, M Yu, Z Xu* (2011). Expression of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibits the Processing of uMtCK to Induce Cell Death in cell culture model system. Biosci Rep 31(5):429-437.
49. Y Sun, T Fei, T Yang, F Zhang, Y Chen, Z Xu* (2010) The suppression of CRMP2 expression by BMP-SMAD gradient signaling controls multiple stages of neuronal development. J Biol Chem. 285(50): 39039–39050.
50. Ren J., Wang Y., Liang Y....and Xu Z* (2010) Methylation of ribosomal protein s10 by protein arginine methyltransferase 5 regulates ribosome biogenesis J Biol Chem. 285(17):12695-705.
51. C Wang, Y Tao, Y Wang, Z Xu* Regulation of the Protein Stability of POSH and MLK Family. Protein Cell 1(9): 871–878.
52.Y Sun, Z Xu* (2010) Regulation of Neural Stem Cell by Bone Morphogenic Protein (BMP) Signaling During Brain Development. Frontiers in Biology 5(5):380-385.
53. B Lu; Y Zhai, C Wu; X Pang, Z Xu, F Sun (2010) Expression, purification and preliminary biochemical studies of the N-terminal domain of leucine-rich repeat kinase 2. BBA-Proteins and Proteomics 804(9):1780-4.
54. M Zhang, Y Zhang and Z Xu* (2010) POSH is Involved in Egr-Bsk (TNF-JNK) Signaling and Embryogenesis in Drosophila. J Genetics and Genomics 37(9):605-19.
55. Shen Q, Qin F, Gao Z, Cui J, Xu Z, and Yang C (2009) Adenine Nucleotide Translocator Cooperates with Core Cell Death Machinery to Promote Apoptosis in Caenorhabditis elegans. Mol Cell Biol, 29(14): 3881–3893.
56. Jin S, Pan L, Liu Z, Wang Q, Xu Z, and Zhang Y (2009) Drosophila Tubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation. Development 136(9):1571-81.
57. Sproul A , Xu Z and Greene L (2009) Cbl Negatively Regulates JNK Activation and Cell Death. Cell Research 19(8):950-61.
58. Liu S, Yu M, He Y, Xiao L,…, and Xu Z* (2008) Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway. Hepatology 47(6) 1964-73.
59. Qiao HX, Hao CJ, Li Y, He X, Chen RS, Cui J, Xu Z*, Li W*.（2008） JNK activation mediates the apoptosis of xCT-deficient Cells. BBRC 370(4):584-8.
60. Sun Y, Yang T, Xu Z* (2007) The JNK Pathway and Neuronal Migration. J Genetics and Genomics 34(11): 957-965.
61. Wilhelm M, Kukekov NV, Xu Z, Greene LA (2007) Identification of POSH2, a novel homologue of the c-Jun N-terminal kinase scaffold protein POSH. Dev Neurosci. 29(4-5):355-62.
62. Wang L, Zhang Y, Li H, Xu Z, Santella RM, Weinstein IB. (2007) Hint1 Inhibits Growth and Activator Protein-1 Activity in Human Colon Cancer Cells. Cancer Res. 67(10):4700-4708.
63. Cui J, Zhang M, Zhang YQ, Xu Z* (2007) JNK pathway: diseases and therapeutic potential. Acta Pharmacol Sin. 28(5):601-8.
64. Welhelm M, Xu Z., and Greene L （2007）Proapoptotic Nix activates the JNK pathway by interacting with POSH and mediates death in a Parkinson disease model. J Biol Chem. 282(2):1288-95.
65. Xu Z.*, Sproul A., Wang WY, and Greene L. (2006) SIAH1 Interacts with the Scaffold Protein POSH to Promote JNK Activation and Apoptosis. J Biol Chem. 281(1):303-12.
(* Corresponding author)
66. Kukekov, N*.,Xu Z.*, and Greene(2006) Direct interaction of the molecular scaffolds POSH and JIP is required for apoptotic activation of JNKs. J Biol Chem. 281(22):15517-24.
(* Equal contribution)
67. Tang G, Xu Z, Goldman JE. (2006) Synergistic effects of the SAPK/JNK & the proteasome pathways on GFAP accumulation in Alexander disease. J Biol Chem. 281(50):38634-43.
68. Xu Z.*, Kukekov, N., and Greene L (2005) A stability-based self-amplifying feed forward loop mechanism for regulation of the apoptotic JNK pathway. Mol Cell Biol. 25(22):9949-59.
(* Corresponding author)
69. Xu Z.* and Greene L. (2006) Activation of the apoptotic JNK pathway through the Rac1-binding scaffold protein POSH. Methods Enzymol 406:479-89. (* Corresponding author)
70. Zheng S.*, Xu Z.*^¨, and Longey J. (2005) Cbl-b/Cbl regulates c-Kit receptor stability through the proteasomal pathway in mast cells. Blood 105(1):226-32. (* Equal contribution, ^¨ Corresponding author).
71. Hanlon SE, Xu Z, Norris DN, Vershon AK. (2004) Analysis of the meiotic role of the mitochondrial ribosomal proteins Mrps17 and Mrpl37 in Saccharomyces cerevisiae. Yeast. 21(15):1241-52.
72. Kim K., Kim B., Xu Z, and Kim S. (2004). Mixed lineage kinase (MLK) 3-activated p38 MAP kinase mediates TGF-Beta-induced apoptosis in hepatoma cells. J Biol Chem. 279(28):29478-84.
73. Xu Z., Kukekov N., and Greene LA (2003). POSH (plenty of SH3’s) Acts as a Scaffold for a Multiprotein Complex that Mediates JNK Activation in Apoptotic Death. EMBO J 15; 22(2): 252-61.
74. Xu Z, Maroney AC, Dobrzanski P, Greene LA (2001). The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis. Mol Cell Biol. 21(14): 4713-24.
75. Maroney AC, Finn JP, Connors TJ, Durkin JT, Angeles T, Gessner G, Xu Z, Meyer SL, Savage MJ, Greene LA, Scott RW, Vaught JL (2001). Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J Biol Chem. 276(27): 25302-8.
76. Troy CM, Rabacchi SA, Xu Z, Maroney AC, Connors TJ, Shelanski ML, Greene LA (2001). beta-Amyloid-induced neuronal apoptosis requires c-Jun N-terminal kinase activation. J Neurochem. 77(1):157-64.
77. Xu Z., and Norris D. (1999). The SFP1 gene product of S. cerevisiae regulates G2/M transitions in the mitotic cell cycle and in response to DNA damage. Genetics 150(4): 1419-28.