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師資隊(duì)伍
徐天樂
  作者:  2021-03-25

基本信息 >>>

                                                                                                                                                                                                 
    徐天樂

    神經(jīng)細(xì)胞信號(hào)調(diào)控研究組

  電話:63846590-778022

  郵箱:[email protected]


研究方向>>>

神經(jīng)系統(tǒng)中離子通道功能調(diào)控及其機(jī)理。蛋白質(zhì)是生命活動(dòng)的主要執(zhí)行者,。由蛋白質(zhì)大分子復(fù)合體構(gòu)成的離子通道是單個(gè)細(xì)胞功能和整體生命活動(dòng)的基礎(chǔ),,涉及生殖細(xì)胞受精,、心臟節(jié)律維持和大腦高級(jí)認(rèn)知功能等,。離子通道異常導(dǎo)致許多常見病如高血壓,、心律失常和神經(jīng)精神疾病等,。因此,離子通道是疾病治療的重要藥物靶標(biāo),。對(duì)離子通道的深入研究一直是醫(yī)學(xué),、生命科學(xué)尤其是神經(jīng)科學(xué)的前沿。隨著蛋白質(zhì)晶體學(xué)和冷凍電鏡技術(shù)在膜蛋白(包括離子通道)結(jié)構(gòu)解析中的發(fā)展應(yīng)用,,多學(xué)科交叉的技術(shù)方法為發(fā)現(xiàn)離子通道新的生物學(xué)功能和開展靶向特定通道功能域的合理藥物設(shè)計(jì)開辟了嶄新和廣闊的前景,。我們致力于離子通道的基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)研究,主要研究?jī)?nèi)容包括:

 

1. 離子通道與神經(jīng)環(huán)路

2. 學(xué)習(xí)記憶及相關(guān)疾病

3. 腦疾病的藥物新靶標(biāo)

     

個(gè)人簡(jiǎn)歷 >>>

上海交通大學(xué)醫(yī)學(xué)院特聘教授,。中國(guó)神經(jīng)科學(xué)學(xué)會(huì)常務(wù)理事,;中國(guó)生理學(xué)會(huì)常務(wù)理事;上海市神經(jīng)科學(xué)學(xué)會(huì)理事長(zhǎng),。研究領(lǐng)域?yàn)樯窠?jīng)系統(tǒng)中離子通道功能調(diào)控及其機(jī)理,。主持科技部重大科學(xué)研究計(jì)劃973項(xiàng)目和國(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目等,在酸敏感離子通道新配體,、新功能以及調(diào)控新機(jī)制等方面取得了一些在國(guó)內(nèi)外學(xué)術(shù)界有影響的成果,。研究成果以通訊作者或共同通訊作者身份發(fā)表在NeuronNature Communications,,Science Advances,,Science SignalingPLoS Biology,,Brain,,eLifeCell ReportsJournal of Neuroscience等,。擔(dān)任Frontiers in Pharmacology of Ion Channel and Channelopathies,,ChannelsACS Chemical Neuroscience,,Molecular Pain,,Scientific ReportsNeuroscience Bulletin等國(guó)際學(xué)術(shù)期刊的編委。曾先后擔(dān)任中國(guó)科技大學(xué)神經(jīng)生物學(xué)與生物物理學(xué)系主任,、中科院神經(jīng)科學(xué)研究所所長(zhǎng)助理、中科院神經(jīng)生物學(xué)重點(diǎn)實(shí)驗(yàn)室副主任,,神經(jīng)科學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室常務(wù)副主任,,蘇州大學(xué)醫(yī)學(xué)部主任、上海交通大學(xué)基礎(chǔ)醫(yī)學(xué)院暨醫(yī)學(xué)科學(xué)研究院院長(zhǎng),、解剖學(xué)與組織胚胎學(xué)系主任等職務(wù),。目前擔(dān)任上海交通大學(xué)醫(yī)學(xué)院基礎(chǔ)醫(yī)學(xué)院教授委員會(huì)主任,解剖學(xué)與生理學(xué)系主任和神經(jīng)科學(xué)研究生培養(yǎng)計(jì)劃負(fù)責(zé)人,,國(guó)家兒童醫(yī)學(xué)中心(上海)兒童腦科學(xué)中心主任,。


科研項(xiàng)目 >>>

1)國(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目《恐懼記憶消退后重現(xiàn)的神經(jīng)生物學(xué)機(jī)制》(2020-2024

2)國(guó)際(地區(qū))合作與交流項(xiàng)目(中美)《慢性痛大腦皮層可塑性的新機(jī)制研究》(2020-2024

3)上海市科委基礎(chǔ)研究重點(diǎn)課題《感知認(rèn)知神經(jīng)網(wǎng)絡(luò)的功能及其障礙機(jī)制》(2018-2021

4)上海市《全腦神經(jīng)聯(lián)接圖譜與克隆猴模型計(jì)劃》市級(jí)科技重大專項(xiàng)課題《恐懼記憶消退的介觀神經(jīng)環(huán)路基礎(chǔ)研究》(2018-2023

5)國(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目《靶向酸敏感離子通道調(diào)控新機(jī)制的系統(tǒng)藥理學(xué)研究》(2018-2022


論文與專著 >>>

代表性論文(#共同第一作者,;*通訊作者或共同通訊作者)

1.Wang JJ#, Liu F#, Yang F, Wang YZ, Qi X, Li Y, Hu Q*, Zhu MX*, Xu TL* (2020) Disruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis. Nature Communications 11(1): 475.

2.Su X#, Chen M#, Yuan Y, Li Y, Guo SS, Luo HQ, Huang C, Sun W, Li Y, Zhu MX, Liu MG*, Hu J*, Xu TL* (2019) Central Processing of Itch in the Midbrain Reward Center. Neuron, 102, 1-15.

3.Wang Q#, Wang Q#, Song XL, Jiang Q, Wu YJ, Li Y, Yuan TF, Zhang S, Xu NJ, Zhu MX, Li WG*, Xu TL* (2018) Fear extinction requires ASIC1a-dependent regulation of hippocampal-prefrontal correlates. Science Advances, 4(10):eaau3075.

4.Yu Z#, Wu YJ#, Wang YZ, Liu DS, Song XL, Jiang Q, Li Y, Zhang SY, Xu NJ, Zhu MX, Li WG*, Xu TL* (2018) ASIC1a mediates striatal synapse remodeling and procedural motor learning. Science Signaling, 11(542). pii: eaar4481.

5.Li WG#, Liu MG#, Deng S#, Liu YM, Shang L, Ding J, Hsu TT, Jiang Q, Li Y, Li F*, Zhu MX*, Xu TL* (2016) ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion. Nature Communications, 7: 13770.

6.Wang YZ#, Wang JJ#, Huang Y, Liu F, Zeng WZ, Li Y, Xiong ZG, Zhu MX, Xu TL* (2015) Tissue acidosis induces neuronal necroptosis via ASIC1a channel independent of its ionic conduction. eLife.4: e05682.

7.Peng Z#, Li WG#, Huang C, Jiang YM, Wang X, Zhu MX, Cheng X*, Xu TL* (2015) ASIC3 mediates itch sensation in response to coincident stimulation by acid and nonproton ligand. Cell Reports, 13(2): 387-398.

8.Wang YZ, Zeng WZ, Xiao X, Huang Y, Song XL, Yu Z, Tang D, Dong XP, Zhu MX, Xu TL* (2013) Intracellular ASIC1a regulates mitochondrial permeability transition-dependent neuronal death. Cell Death and Differentiation, 20: 1359-1369.

9.Zeng WZ, Liu DS, Duan B, Song XL, Wang X, Wei D, Jiang W, Zhu MX, Li Y, Xu TL* (2013) Molecular mechanism of constitutive endocytosis of acid-sensing ion channel 1a and its protective function in acidosis-induced neuronal death. Journal of Neuroscience, 33(16): 7066-7078.

10.Wang X, Li WG, Yu Y, Xiao X, Cheng J, Zeng WZ, Peng Z, Zhu MX, Xu TL* (2013) Serotonin facilitates peripheral pain sensitivity in a manner that depends on the nonproton ligand sensing domain of ASIC3 channel. Journal of Neuroscience, 33(10): 4265-4279.

11.Duan B#, Liu DS#, Huang Y, Zeng WZ, Wang X, Yu H, Zhu MX, Chen ZY, Xu TL* (2012) PI3-kinase/Akt pathway-regulated membrane insertion of Acid-sensing ion channel 1a underlies BDNF-induced pain hypersensitivity. Journal of Neuroscience, 32(18): 6351-6363.

12.Duan B#, Wang YZ#, Yang T, Chu XP, Yu Y, Huang Y, Cao H, Hansen J, Simon RP, Zhu MX, Xiong ZG, Xu TL* (2011) Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. Journal of Neuroscience, 31: 2101-2112.

13.Yu Y#, Chen Z#, Li WG#, Cao H, Feng EG, Yu F, Liu H, Jiang H*, Xu TL* (2010) A non-proton ligand sensor in the acid-sensing ion channel. Neuron, 68: 61-72.

14.Pan X#, Gong N#, Zhao J, Yu Z, Gu F, Chen J, Sun X, Zhao L, Yu M, Xu Z, Dong W, Qin Y, Fei G, Zhong C*, Xu TL* (2010) Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. Brain, 133(5): 1342-1351.

15.Xu TL*, Gong N (2010) Glycine and glycine receptor signaling in hippocampal neurons: diversity, function and regulation. Progress in Neurobiology, 91(4): 349-361.

16.Yang H#, Yu Y#, Li WG, Yu F, Cao H, Xu TL*, Jiang H* (2009) Inherent dynamics of the acid-sensing ion channel 1 correlates with the gating mechanism. PLoS Biology, 7(7): e1000151.

17.Xu TL*, Duan B (2009) Calcium-permeable acid-sensing ion channel in nociceptive plasticity: a new target for pain control. Progress in Neurobiology, 87(3): 171-180.

18.Gong N, Li Y, Cai GQ, Niu RF, Fang Q, Wu K, Chen Z, Lin LN, Xu L, Fei J, Xu TL* (2009) GABA transporter-1 activity modulates hippocampal theta oscillation and theta burst stimulation-induced long-term potentiation. Journal of Neuroscience, 29: 15836-15845.

19.Zhang Z, Gong N, Wang W, Xu L, Xu TL* (2008) Bell-shaped D-serine actions on hippocampal long-term depression and spatial memory retrieval. Cerebral Cortex, 18(10): 2391-2401.

20.Zhang LH#, Gong N#, Fei D, Xu L, Xu TL* (2008) Glycine uptake regulates hippocampal network activity via glycine receptor-mediated tonic inhibition. Neuropsychopharmacology, 33(3):701-711.

21.Duan B, Wu LJ, Yu YQ, Ding Y, Jing L, Xu L, Chen J*, Xu TL* (2007) Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. Journal of Neuroscience, 27: 11139-11148.

22.Gao J, Duan B, Wang DG, Deng XH, Zhang GY, Xu L, Xu TL* (2005) Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death. Neuron, 48: 635-646.

專著

《中國(guó)大百科全書》第三版(參編)

《生理學(xué)名詞》第二版(參編)

《神經(jīng)科學(xué)》第三版(參編);韓濟(jì)生主編

《神經(jīng)生物學(xué)》第三版(參編),;壽天德主編


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指導(dǎo)本科生RBL以及大學(xué)生創(chuàng)新性實(shí)驗(yàn)項(xiàng)目


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