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科學(xué)研究
神經(jīng)細(xì)胞發(fā)育與腦功能失調(diào)研究組
  作者：  2020-12-18

徐楠杰

神經(jīng)細(xì)胞發(fā)育與腦功能失調(diào)研究組

電話：021-34696293；

郵箱：[email protected]

地址：上海市黃浦區(qū)重慶南路280號(hào) 上海交通大學(xué)醫(yī)學(xué)院 西5號(hào)樓303室



徐楠杰研究員，博士生導(dǎo)師，解剖學(xué)與生理學(xué)系副主任， “神經(jīng)細(xì)胞發(fā)育與腦功能失調(diào)”研究組組長(zhǎng)。入選國(guó)家海外高層次人才計(jì)劃，上海市浦江人才計(jì)劃。擔(dān)任中國(guó)細(xì)胞生物學(xué)會(huì)神經(jīng)細(xì)胞生物學(xué)分會(huì)會(huì)長(zhǎng)，中國(guó)細(xì)胞生物學(xué)學(xué)會(huì)科普工作委員會(huì)副主委、青年工作委員會(huì)委員，中國(guó)神經(jīng)科學(xué)學(xué)會(huì)神經(jīng)發(fā)育與再生分會(huì)委員，上海市神經(jīng)科學(xué)學(xué)會(huì)理事。主要工作發(fā)表于Nature Neuroscience，Nature Communications，Science Advances，Molecular Psychiatry， Journal of Cell Biology，Journal of Neuroscience等本領(lǐng)域一流國(guó)際期刊。


研究方向

研究興趣集中在神經(jīng)干細(xì)胞發(fā)育，神經(jīng)連接和突觸形成過(guò)程中的受體信號(hào)和神經(jīng)系統(tǒng)疾病的發(fā)生機(jī)制。

  1. 成體神經(jīng)干細(xì)胞發(fā)育和神經(jīng)功能

    神經(jīng)干細(xì)胞/祖細(xì)胞和神經(jīng)前體細(xì)胞存在于發(fā)育過(guò)程中和成年的腦中，對(duì)于神經(jīng)環(huán)路的維持和更新起著關(guān)鍵作用。酪氨酸激酶受體參與調(diào)節(jié)神經(jīng)干細(xì)胞的多個(gè)發(fā)育過(guò)程，如增殖，遷移，分化和譜系可塑性等。我們的研究目標(biāo)是解析成體神經(jīng)干細(xì)胞中受體信號(hào)并闡明環(huán)境刺激對(duì)神經(jīng)干細(xì)胞的命運(yùn)的調(diào)節(jié)作用。

  2. 神經(jīng)環(huán)路的形成和功能

    長(zhǎng)距離神經(jīng)環(huán)路連接過(guò)程中如何整合外界信號(hào)到腦內(nèi)的認(rèn)知和情感關(guān)鍵核團(tuán)如海馬，伏隔核， 杏仁核和腹側(cè)背蓋區(qū)，以及這些核團(tuán)之間如何相互交流，進(jìn)而調(diào)節(jié)情緒，獎(jiǎng)賞，學(xué)習(xí)和記憶等高級(jí)神經(jīng)活動(dòng)仍然是尚待解決的問(wèn)題。我們感興趣并要闡明的兩個(gè)問(wèn)題是：1）神經(jīng)酪氨酸激酶受體配體結(jié)合介導(dǎo)的神經(jīng)細(xì)胞聯(lián)系在關(guān)鍵神經(jīng)核團(tuán)之間形成的神經(jīng)環(huán)路中的作用；2）神經(jīng)受體介導(dǎo)的神經(jīng)環(huán)路的形成如何支持重要腦功能的產(chǎn)生。

  3. 神經(jīng)精神疾病的分子細(xì)胞機(jī)制

    Eph/ephrin和谷氨酸受體如NR1，mGluR5等受體的相互作用成為許多神經(jīng)精神疾病的關(guān)鍵環(huán)節(jié)。我們?cè)谏窠?jīng)發(fā)育性和神經(jīng)退行性疾病的模型中，如孤獨(dú)癥和阿爾茨海默病等病理?xiàng)l件下探討Eph/ephrin受體及其介導(dǎo)的信號(hào)對(duì)谷氨酸受體的調(diào)節(jié)作用，尋求腦疾病發(fā)生的神經(jīng)和分子機(jī)制。


 

 

科研項(xiàng)目


  1. 國(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目：出生后發(fā)育期社交行為的突觸發(fā)生和環(huán)路形成機(jī)制（2021-2025）

  2. 國(guó)家自然科學(xué)基金面上項(xiàng)目：阿爾茨海默病早期異常情感表征和認(rèn)知環(huán)路調(diào)節(jié)機(jī)制（2019 -2022）

  3. 國(guó)家自然科學(xué)基金面上項(xiàng)目：PDZ蛋白Lnx1介導(dǎo)的海馬神經(jīng)環(huán)路發(fā)育和可塑性機(jī)制 （2017-2020）

  4. 國(guó)家自然科學(xué)基金面上項(xiàng)目：EphB受體信號(hào)介導(dǎo)的神經(jīng)干細(xì)胞分化機(jī)制 （2014-2017）

  5. 國(guó)家重點(diǎn)基礎(chǔ)研究發(fā)展計(jì)劃（973項(xiàng)目子課題）：調(diào)控前腦神經(jīng)祖細(xì)胞發(fā)育過(guò)程的微環(huán)境解析（2014-2018）

  6. 國(guó)家自然科學(xué)基金重大研究計(jì)劃培育項(xiàng)目：Eph-ephrin受體信號(hào)介導(dǎo)的情感和記憶相關(guān)神經(jīng)環(huán)路的發(fā)育機(jī)制 （2013-2015）

  7. 國(guó)家自然科學(xué)基金面上項(xiàng)目：神經(jīng)軸突剪切的Eph-ephrin雙向信號(hào)轉(zhuǎn)導(dǎo)（2012-2012）

 


代表性論文、專(zhuān)著與專(zhuān)利


  1. Wu XR (吳欣蓉)#, Zhang Y (張?jiān)?#, Liu XD, Han WB, Xu NJ*, Sun S*. EphB2 mediates social isolation-induced memory forgetting. Transl Psychiatry, 10:389 (2020).

  2. Ai PH (艾鵬輝)#, Chen S (陳偲)#, Liu XD, Zhu XN, Pan YB, Feng DF, Chen SD, Xu NJ*, Sun S*. Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice. Transl Neurodegener, 9:18 (2020).

  3. Liu XD (劉賢東)#, Ai PH (艾鵬輝)#, Zhu XN, Pan YB, Halford MM, Henkemeyer M, Feng DF, Xu TL, Sun S*, Xu NJ*. Hippocampal Lnx1-NMDAR multi-protein complex mediates initial social memory. Mol Psychiatry, doi:10.1038/s41380-019-0606-y (2019).

  4. Dong J (董健), Pan YB, Wu XR, He LN, Liu XD, Feng DF, Xu TL, Sun S*, Xu NJ*. A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells. Sci Adv, 5: eaav4416 (2019).

  5. Liu XD (劉賢東), Zhu XN, Halford MM, Xu TL, Henkemeyer M, Xu NJ*. Retrograde regulation of mossy fiber axon targeting and terminal maturation via postsynaptic Lnx1. J Cell Biol, 217: 4007-4024 (2018).

  6. Huang GH (黃國(guó)輝)#, Guo L (郭霖)#, Zhu L, Liu XD, Sun ZL, Li HJ, Xu NJ*, Feng DF*. Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth. Cell Mol Life Sci, 75: 4207-4222 (2018).

  7. Zhu XN (朱曉娜), Liu XD, Zhuang H, Henkemeyer M, Yang JY*, Xu NJ*. Amygdala EphB2 signaling regulates glutamatergic neuron maturation and innate fear. J Neurosci, 36(39):10151-10162 (2016).

  8. Zhu XN (朱曉娜), Liu XD, Sun S*, Zhuang H, Yang JY, Henkemeyer M, Xu NJ*. Ephrin-B3 mediates timed axon targeting and amygdala spinogenesis for innate fear behaviour. Nat Commun, 7:11096 (2016).

  9. Sun S, Zhang H, Liu J, Popugaeva E, Xu NJ, Feske S, Bezprozvanny I*. Reduced synaptic STIM2 expression and impaired store-operated calcium entry cause destabilization of mature spines in mutant presenilin mice. Neuron, 81: 79-93 (2014).

  10. Xu NJ*, Henkemeyer M*. Ephrin reverse signaling in axon guidance and synaptogenesis. Semin Cell Dev Biol, 23: 58-64 (2012). (Invited Review)

  11. Xu NJ, Sun S, Gibson J and Henkemeyer M*. A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses. Nat Neurosci, 14: 1421-1429 (2011).

  12. Genander M, Halford MM, Xu NJ, Eriksson M, Yu Z, Qiu Z, Martling A, Greicius G, Chumley MJ, Zdunek S, Wang C, Holm T, Goff SP, Pettersson S, Pestell RG, Henkemeyer M and Frisén J*. Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression. Cell, 139: 679-692 (2009).

  13. Xu NJ, Henkemeyer M*. Ephrin-B3 reverse signaling through Grb4 and downstream cytoskeletal regulators mediates axon pruning. Nat Neurosci, 12: 268-276 (2009).

  14. Aoto J, Ting P, Maghsoodi B, Xu NJ, Henkemeyer M, Chen L*. Postsynaptic ephrinB3 promotes shaft glutamatergic synapse formation. J Neurosci, 27: 5708-19 (2007).

  15. Armstrong JN, Saganich MJ, Xu NJ, Henkemeyer M, Heinemann SF, Contractor A*. B-ephrin reverse signaling is required for NMDA-independent long-term potentiation of mossy fibers in the hippocampus. J Neurosci, 26: 3474-81 (2006).

  16. Xu NJ#, Yu YX#, Zhu JM, Liu H, Shen L, Zen R, Zhang X, Pei G*. Inhibition of SNAP-25 phosphorylation at Ser187 is involved in chronic morphine-induced down-regulation of SNARE complex formation. J Biol Chem, 279: 40601-8 (2004).

  17. Xu NJ, Bao L, Fan HP, Bao GB, Pu L, Lu YJ, Wu CF, Zhang X, Pei G*. Morphine withdrawal increases neuronal glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses. J Neurosci, 23: 4775-4784 (2003).

  18. Pu L, Bao GB, Xu NJ, Ma L, Pei G*. Hippocampal long-term potentiation is reduced by chronic opiate treatment and can be restored by re-exposure to opiates. J Neurosci, 22: 1914-21 (2002).

  19. Lu L, Xu NJ, Ge X, Yue W, Su WJ, Pei G, Ma L*. Reactivation of morphine conditioned place preference by drug priming: role of environmental cues and sensitization. Psychopharmacology, 159: 125-132 (2002).

 

團(tuán)隊(duì)介紹


實(shí)驗(yàn)室畢業(yè)博士研究生（含聯(lián)合培養(yǎng)）:

  1. 朱曉娜博士 2012.8-2016.6 （聯(lián)培），博士后 2016.9-2018.12

  2. 劉賢東博士 2013.4-2018.12， 博士后2019.1-

  3. 董健博士 2013.5-2019.6

  4. 黃國(guó)輝博士 2013.6-2017.6 （聯(lián)培）

  5. 郭霖博士 2014.5-2018.12