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刘佳佳


刘佳佳,博士,研究员,博士生导师
        1991年武汉大学学士;1994年中国科学院上海细胞生物学研究所硕士;2000年芝加哥大学分子遗传及细胞生物学博士;2000-2005在斯坦福大学医学中心神经科学系从事博士後研究。2013年获“国家杰出青年基金”资助及中国科学院优秀导师奖。


主要研究方向:以培养细胞系、原代神经元以及小鼠为模型,研究细胞内分子马达驱动的囊泡运输调控机制,膜运输及细胞骨架重塑调控神经发育和可塑性及人类相关疾病的分子机制。
 
主要研究内容:
        1. 分子马达对囊泡货物的精确识别及卸载机制。 
        囊泡运输是真核细胞中主要的物质与信息交流形式。已知在细胞中心/细胞体和细胞外周/神经末梢之间转运的囊泡货物有多种类型,例如在神经元中神经营养因子及其受体被内吞包装形成的signaling endosome及其它内吞小泡、自噬小体、溶酶体和线粒体等。驱动运输的分子马达可能通过和介导分子(cargo adaptor)或调控因子作用,实现对各种货物的识别、长程运输及精确卸载。我们先前的研究发现了若干参与调控dynein-dynactin运输的蛋白质因子和脂分子,并解析了它们所参与的逆向囊泡运输通路及其功能。我们将继续运用分子遗传学、细胞生物学和生物化学手段,寻找参与囊泡运输的蛋白质和脂分子并解析它们的功能,探讨它们在囊泡货物识别、分选及释放中的作用。

        2.囊泡运输调控神经发育及功能的分子机制
        神经元是高度极性化的细胞,神经元的发育、存活及功能维持都依赖于神经元轴突及树突中的囊泡运输。我们致力于解析中枢神经元树突中的囊泡运输途径,通过免疫纯化及质谱分析鉴定我们感兴趣的运输调节因子在神经元中介导运输的囊泡货物,并通过对于运输调节因子的神经特异性敲除小鼠的表型分析,深入探讨它们在神经元中通过囊泡运输调控神经发育与功能的作用机制。
 
        3. 兴奋性神经突触可塑性的分子细胞机制
        树突棘是兴奋性突触信号的主要接收位点,树突棘的结构和功能可塑性是学习和记忆的分子细胞基础。我们尝试解析在神经活性依赖的突触可塑性发生时细胞骨架重塑和膜运输这两种细胞活动协同发生导致树突棘形状及功能改变的机制,鉴定树突棘中时空特异性调控微丝细胞骨架重塑及膜运输的信号通路及相关调节因子,并运用活细胞成像及超高分辨显微技术观测树突棘亚细胞结构和组分的动态变化。
 
博士后招聘信息:
        本实验室目前拟招聘1名博士后。详情请联系jjliu@genetics.ac.cn
发表论文:
Yang Y., Liu JJ. (2022) Structural LTP: signal transduction, actin cytoskeleton reorganization, and membrane remodeling of dendritic spines. Curr Opin Neurobiol. 74:102534. doi: 10.1016/j.conb.2022.102534. Invited review.
 
Guo Z.#, Jiang CH.#, Tong C., Yang Y., Wang Z., Lam SM., Wang D., Li R., Shui G., Shi YS., Liu JJ. (2022) Activity-dependent PI4P synthesis by PI4KIIIa regulates long-term synaptic potentiation. Cell Rep. 38 (9), 110452. doi: 10.1016/j.celrep.2022.110452
 
Togo J., Yang Y., Hu S, Liu JJ.*, Speakman JR.* (2022) Effect of disrupted episodic memory on food consumption: no impact of neuronal loss of Endophilin A1 on food intake and energy balance. J Genet Genomics 49 (4), 329-337. doi: 10.1016/j.jgg.2022.01.005
 
Yang Y.#*, Chen J. #, Chen X., Li D., He J., Wang S., Zhao S., Yang X., Deng S., Tong C., Wang D., Guo Z., Li D., Ma C., Liang X., Shi SY., and Liu JJ.* (2021) Endophilin A1 drives acute structural plasticity of dendritic spines in response to Ca2+/calmodulin. J Cell Biol. 220 (6): e202007172. doi: 10.1083/jcb.202007172
 
Liu A.#, Huang X.#, He W., Xue F., Yang Y., Liu JJ., Chen L., Yuan L., Xu P. (2021) pHmScarlet is a pH-sensitive red fluorescent protein to monitor exocytosis docking and fusion steps. Nat Commun. 2021 Mar 3; 12(1):1413. doi: 10.1038/s41467-021-21666-7
 
Dong X., Zhou J., Qin HB., Xin B., Huang ZL., Li YY., Xu X., Zhao F., Zhao C., Liu JJ.*, Luo MH., WB Zeng.* (2020) Anterograde Viral Tracer HSV-1 Strain H129 Transports Primarily as Capsids in Cortical Neuron Axons. J Virol.  2020 Mar 31;94(8):e01957-19. doi: 10.1128/jvi.01957-19
 
Guo Y., Li D., Zhang S., Yang Y., Liu JJ., Wang X., Liu C., Milkie DE, Moore RP, Tulu US., Kiehart DP., Hu J, Lippincott-Schwartz J., Betzig E. and Li D. (2018) Visualizing intracellular organelle and cytoskeletal interactions at nanoscale resolution on millisecond time scales. Cell. doi: 10.1016/j.cell.2018.09.057
 
Yang Y.#*, Chen J. #, Guo Z., Deng S., Du X., Zhu S., Ye C., Shi SY., and Liu JJ.* (2018) Endophilin A1 promotes actin polymerization in dendritic spines required for synaptic potentiation. Front. Mol. Neurosci. May 28 2018. doi: 10.3389/fnmoli.2018.00177, 2018
 
Sun Q., Yong X., Sun X., Yang F., Dai Z., Gong Y., Zhou Li., Zhang X., Niu D., Dai L., Liu JJ. and Jia D. (2017) Structural and functional insights into sorting nexin 5/6 interaction with bacterial effector IncE. Signal Transduct Target Ther.  2, e17030; doi: 10.1038/sigtrans.2017.30.
 
Li MY., Miao WY., Wu QZ., He SJ., Yan G., Yang Y., Liu JJ., Taketo MM. and Yu X. (2017) A critical role of presynaptic Cadherin/Catenin/p140Cap complexes in stabilizing spines and functional synapses in the neocortex. Neuron. 94 (6), 1155-1172. doi: 10.1016/j.neuron.2017.05.022.
 
Liu JJ. (2017) Regulation of dynein-dynactin-driven vesicular transport. Traffic. 18 (6), 336-347. doi: 10.1111/tra.12475. Invited review.
 
Niu, Y. #, Dai, Z. #, Liu, W. #, Zhang, C., Yang, Y., Guo, Z., Li, X., Xu, C., Huang, X., Wang, Y., Shi, Y. S.* and Liu, JJ.* (2017) Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory. Elife.  2017 Jan 30; 6. pii: e20991. doi: 10.7554/eLife.20991.
 
Xu C., Fu X., Zhu S. and Liu JJ. (2016) Retrolinkin recruits the WAVE1 protein complex to facilitate BDNF-induced TrkB endocytosis and dendrite outgrowth. Mol Biol Cell. 27 (21), 3342-3356, 2016. doi: 10.1091/mbc.E16-05-0326.
 
Guan L., Ma X., Zhang J., Liu JJ., Wang Y. and Ding M. (2016) The Calponin Family Member CHDP-1 Interacts with Rac/CED-10 to Promote Cell Protrusions. PLoS Genet. 12(7):e1006163, 2016. doi: 10.1371/journal.pgen.1006163.
 
Liu JJ. (2016) Retromer-mediated protein sorting and vesicular trafficking. J Genet Genomics. 43 (4), 165-177. doi: 10.1016/j.jgg.2016.02.006. Review.
 
Yang Y., Wei M., Xiong Y., Du X., Zhu S., Yang L., Zhang C. and Liu JJ. (2015) Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap. Cell Res. 25 (4), 496–516. doi: 10.1038/cr.2015.31. 
 
Li K, Yang L, Zhang C, Niu Y, Li W and Liu JJ. (2014) HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking and maturation of lysosomes. J Cell Sci. 127 (Pt21), 4574-4588. doi: 10.1242/jcs.141978. 
 
Niu Y., Zhang C., Sun Z., Hong Z., Li K., Sun D., Yang Y., Tian C., Gong W., and Liu JJ. (2013) PtdIns(4)P regulates retromer-motor interaction to facilitate dynein-cargo dissociation at the trans-Golgi network. Nat Cell Biol. 15(4), 417-29. doi: 10.1038/ncb2710. 
 
Fu X., Yang Y., Xu C., Niu Y., Chen T., Zhou Q. and Liu JJ. (2011) Retrolinkin cooperates with endophilin A1 to mediate BDNF-TrkB early endocytic trafficking and signaling from early endosomes. Mol Biol Cell. 22 (19), 3684-98. doi: 10.1091/mbc.E11-04-0308.
 
Hong Z#., Yang Y.#, Zhang C., Niu Y., Li K., Zhao X. and Liu JJ. (2009) The retromer component SNX6 interacts with dynactin p150Glued and mediates endosome-to-TGN transport. Cell Res. 19 (12), 1334-49. doi: 10.1038/cr.2009.
 
Xiao H., Chen D., Fang Z., Xu J., Sun X., Song S., Liu JJ. and Yang C. (2009) Lysosome biogenesis mediated by Vps-18 affects apoptotic cell degradation in Caenorhabditis elegans. Mol Biol Cell. 20 (1), 21-32. doi: 10.1091/mbc.E08-04-0441.