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師資隊(duì)伍
徐天樂(lè)
  作者:  2021-01-06

基本信息 >>>


   
徐天樂(lè)
   
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(jiàn)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(kāi)展靶向特定通道功能域的合理藥物設(shè)計(jì)開(kāi)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(zhuān)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(zhuān)著 >>>

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.

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