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李毓龙

邮  箱: yulongli (AT) pku.edu.cn

职  称:教授

办公室地址:北京市海淀区颐和园路5号,北京大学,吕志和楼,100871

所属实验室:李毓龙实验室

实验室地址:北京市海淀区颐和园路5号,北京大学,吕志和楼,100871

实验室主页

http://www.yulonglilab.org

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  • 个人简介
  • 科研领域
  • 代表性论文

教育经历:

2000-2006年,博士,神经生物学系,杜克大学
1996-2000年,学士,生命科学学院,北京大学

工作经历:

2020-今,教授,生命科学学院,北京大学
2012-今,研究员,生命科学学院,生命科学联合中心,麦戈文脑研究所,北京大学
2019-2020年,副教授,生命科学学院,北京大学
2012-2019年,助理教授,生命科学学院,北京大学
2006-2012年,博士后,分子和细胞生理学系,斯坦福大学

荣誉奖励:

中国生命科学十大进展,2023
2022年度拜耳中国科研合作奖——拜耳研究员奖,2023
新基石研究员,2023
教育部基础学科拔尖学生培养计划“优秀导师奖”,2020
科学探索奖生命科学奖,2019
国家杰出青年科学基金,2019
第十二届谈家桢生命科学创新奖,2019
张香桐神经科学青年科学家奖,2019
第二十届吴阶平-保罗·杨森医学药学奖(吴杨奖),2019
中国十大医学科技新闻,2018
中国生命科学十大进展,2018
中源协和生命医学奖创新突破奖,2018
绿叶生物医药杰出青年学者奖,2015

学术任职:

2023-今,Neuron,编委
2022-2024,美国神经科学学会,委员会成员
2022-今,National Science Review,编辑
2019-今,Journal of Neurochemistry,编辑

执教课程:

高级神经生物学
生命科学前沿文献阅读讨论
综合科学实验课程
遗传学讨论课
神经生物学进展
现代生物学实验技术原理及其应用
高级生物物理学
心理/神经/脑科学基础
      人的大脑由数十亿的神经元组成,后者又通过数万亿的突触组成复杂的神经网络。不同种类的神经元经过或远或近的投射,通过突触与其他神经元进行信息交流,实现感知觉、决策和运动等高级神经功能。
研究大脑的最大挑战在于脑的高度复杂性。我们实验室集中在神经元通讯的基本结构突触上,从两个层面上开展研究:一是开发前沿的工具,即开发新型成像探针,用于在时间和空间尺度上解析神经系统的复杂功能;二是借助先进的工具探究突触传递的调节机制,特别是在生理及病理条件下对神经递质释放的调节。
具体而言,对于工具开发,我们集中于:
  1,结合光遗传学和荧光成像,无损伤性的研究神经元之间的电突触连接。电突触的异常可导致耳聋、癫痫、脑部肿瘤和心脏功能异常等疾病。
  2,开发可遗传编码的检测神经递质/调质的荧光探针。神经递质/调质是神经元化学突触传递的关键介导分子,与感知、学习和记忆以及情绪密切相关。
利用上述荧光探针,我们的功能性和生理性的研究集中于:
  1,结合双光子成像和可遗传编码的荧光探针,使用果蝇和小鼠作为模式生物,研究嗅觉传导或睡眠过程中脑的工作机制。
  2,寻找上述新型化学递质/调质小分子的对应受体,即寻找“孤儿”受体的配体。
  3,结合生物信息学、分析化学、生物化学、生理学和成像学方法,系统地探索和鉴定潜在的新型小分子神经递质。
Main research articles:
Zhuo, Y.#, Luo, B.#, Yi, X., Dong, H., Miao, X., Wan, J., Williams, J. T., Campbell, M. G., Cai, R., Qian, T., Li, F., Weber, S. J., Wang, L., Li, B., Wei, Y., Li, G., Wang, H., Zheng, Y., Zhao, Y., Wolf, M. E., Zhu, Y., Watabe-Uchida, M., & Li, Y.* (2023). Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo. Nature Methods. 10.1038/s41592-023-02100-w.

Wang, H.#, Qian, T.#, Zhao, Y., Zhuo, Y., Wu, C., Osakada, T., Chen, P., Chen, Z., Ren, H., Yan, Y., Geng, L., Fu, S., Mei, L., Li, G., Wu, L., Jiang, Y., Qian, W., Zhang, L., Peng, W., Xu, M., Hu, J., Jiang, M., Chen, L., Tang, C., Zhu, Y., Lin, D., Zhou, J.-N., & Li, Y.* (2023). A tool kit of highly selective and sensitive genetically encoded neuropeptide sensors. Science, 382(6672), eabq8173.

Wu, Z.#, Cui, Y.#, Wang, H.#, Wu, H., Wan, Y., Li, B., Wang, L., Pan, S., Peng, W., Dong, A., Yuan, Z., Jing, M., Xu, M., Luo, M.*, & Li, Y.* (2023). Neuronal activity-induced, equilibrative nucleoside transporter-dependent, somatodendritic adenosine release revealed by a GRAB sensor. Proceedings of the National Academy of Sciences, 120(14), e2212387120.

Dong, H.#, Li, M.#, Yan, Y., Qian, T., Lin, Y., Ma, X., Vischer, H. F., Liu, C., Li, G., Wang, H., Leurs, R., & Li, Y.* (2023). Genetically encoded sensors for measuring histamine release both in vitro and in vivo. Neuron.

Zeng, J.#*, Li, X.#, Zhang, R., Lv, M., Wang, Y., Tan, K., Xia, X., Wan, J., Jing, M., Zhang, X., Li, Y., Yang, Y., Wang, L., Chu, J., Li, Y., & Li, Y.*. (2023). Local 5-HT signaling bi-directionally regulates the coincidence time window for associative learning. Neuron.

Qian, T.#, Wang, H.#, Wang, P.#, Geng, L., Mei, L., Osakada, T., Wang, L., Tang, Y., Kania, A., Grinevich, V., Stoop, R., Lin, D., Luo, M., & Li, Y.* (2023). A genetically encoded sensor measures temporal oxytocin release from different neuronal compartments. Nature Biotechnology.

Wu, Z.*, He, K., Chen, Y., Li, H., Pan, S., Li, B., Liu, T., Wang, H., Du, J., Jing, M., & Li, Y.* (2021). A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo Neuron, 110(5), 770-782.e775.

Dong, A., He, K., Dudok, B., Farrell, J. S., Guan, W., Liput, D. J., Puhl, H. L., Cai, R., Wang, H., Duan, J., Albarran, E., Ding, J., Lovinger, D. M., Li, B., Soltesz, I., & Li, Y.*. (2021). A fluorescent sensor for spatiotemporally resolved imaging of endocannabinoid dynamics in vivo. Nature Biotechnology.

Wan, J., Peng, W., Li, X., Qian, T., Song, K., Zeng, J., Deng, F., Hao, S., Feng,J., Zhang, P., Zhang, Y., Zou, J., Pan, S., Shin, M., Venton, B. J., Zhu, J. J., Jing, M., Xu, M., Li, Y.*.(2021). A genetically encoded sensor for measuring serotonin dynamics. Nature Neuroscience, https://doi.org/10.1038/s41593-021-00823-7.

Qian, C., Wu, Z., Sun, R., Yu, H., Zeng, J., Rao, Y., & Li, Y. * (2021). Localization, proteomics, and metabolite profiling reveal a putative vesicular transporter for UDP-glucose. eLife, 10, e65417.

Sun, F.#, Zhou, J.#, Dai, B.#, Qian, T., Zeng, J., Li, X., Zhuo, Y., Zhang, Y., Wang, Y., Qian, C., Tan, K., Feng, J., Dong, H., Lin, D.*, Cui, G.*, & Li, Y.*.(2020). Next-generation GRAB sensors for monitoring dopaminergic activity in vivo. Nature Methods, https://doi.org/10.1038/s41592-020-00981-9.

Jing, M.*, Li, Y., Zeng, J., Huang, P., Skirzewski, M., Kljakic, O., Peng, W., Qian, T., Tan, K., Wu, R., Zhang, S., Pan, S., Xu, M., Li, H., Saksida, L. M., Prado, V. F., Bussey, T., Prado, M. A. M., Chen, L., Cheng, H., Li, Y.*.(2020). An optimized acetylcholine sensor for monitoring in vivo cholinergic activity. Nature Methods, https://doi.org/10.1038/s41592-020-0953-2.

Yu, H., Zhao, T., Liu, S., Wu, Q., Johnson, O., Wu, Z., Zhuang, Z., Shi, Y., He, R., Yang, Y., Sun, J., Wang, X., Xu, H., Zeng, Z., Lei, X., Luo, W.* & Li, Y.*. (2019). MRGPRX4 is a bile acid receptor for human cholestatic itch. eLife, 8, e48431.

Feng, J., Zhang, C., Lischinsky, J. E., Jing, M., Zhou, J., Wang, H., Zhang, Y., Dong, A., Wu, Z., Wu, H., Chen, W., Zhang, P., Zou, J., Hires, S. A., Zhu, J. J., Cui, G., Lin, D., Du, J. & Li, Y.* (2019). A Genetically Encoded Fluorescent Sensor for Rapid and Specific In Vivo Detection of Norepinephrine. Neuron, 102(4), 745-761.

Wu, Z.#, Feng, J.#, Jing, M., & Li, Y.* (2019). G protein-assisted optimization of GPCR-activation based (GRAB) sensors. Neural Imaging and Sensing 2019, vol. 10865, p. 108650N. International Society for Optics and Photonics.

Wu, L., Dong, A., Dong, L., Wang, S. Q., & Li, Y*. (2019). PARIS, an optogenetic method for functionally mapping gap junctions. eLife, 8, e43366.

Sun, F.#, Zeng, J.#, Jing, M.#, Zhou, J., Feng, J., Owen, S., Luo, Y., Li, F., Wang, H., Yamaguchi, T., Yong, Z., Gao, Y., Peng, W., Wang, L., Zhang, S., Du, J., Lin, D., Xu, M., Kreitzer, A. C., Cui, G. & Li, Y.* (2018). A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice. Cell, 174(2), 481-496.

Jing, M.#, Zhang, P.#, Wang, G., Feng, J., Mesik, L., Zeng, J., Jiang, H., Wang, S., Looby, J. C., Guagliardo, N. A., Langma, L. W., Lu, J., Zuo, Y., Talmage, D. A., Role, L. W., Barrett, P. Q., Zhang, L. I., Luo, M., Song, Y., Zhu, JJ* & Li, Y*. (2018). A genetically-encoded fluorescent acetylcholine indicator for in vitro and in vivo studies. Nature Biotechnology, 36(8), 726-737.

Li, Y.*, & Tsien, R. W.* (2012). pHTomato, a red, genetically encoded indicator that enables multiplex interrogation of synaptic activity. Nature neuroscience, 15(7), 1047-1053.

Li, Y., Augustine, G. J., & Weninger, K.* (2007). Kinetics of complexin binding to the SNARE complex: correcting single molecule FRET measurements for hidden events. Biophysical journal, 93(6), 2178-2187.

Collaborative publications

Sang, D.#, Lin, K.#, Yang, Y.#, Ran, G., Li, B., Chen, C., Li, Q., Ma, Y., Lu, L., Cui, X.-Y., Liu, Z., Lv, S.-Q., Luo, M., Liu, Q., Li, Y., & Zhang, E. E.* (2023). Prolonged sleep deprivation induces a cytokine-storm-like syndrome in mammals. Cell, 186(25), 5500-5516.e5521.

Terauchi, A., Yee, P., Johnson-Venkatesh, E. M., Seiglie, M. P., Kim, L., Pitino, J. C., Kritzer, E., Zhang, Q., Zhou, J., Li, Y., Ginty, D. D., Lee, W. A., & Umemori, H.# (2023). The projection-specific signals that establish functionally segregated dopaminergic synapses. Cell, https://doi.org/10.1016/j.cell.2023.07.023.

Krok, A. C., Maltese, M., Mistry, P., Miao, X., Li, Y., & Tritsch, N. X.# (2023). Intrinsic dopamine and acetylcholine dynamics in the striatum of mice. Nature, https://doi.org/10.1038/s41586-023-05995-9.

Yu, X., Zhao, G., Wang, D., ...Li, Y., Dong, H.#, Franks, N.# & William, W. # (2022). A specific circuit in the midbrain detects stress and induces restorative sleep. Science, 377, 63-72.

Provencher, V. #, Drummond, G., Feng, J., Li, Y. & Sur, M. # (2022). Spatiotemporal dynamics of noradrenaline during learned behavior. Nature, 606, 732-738.

Liu, C. #, Cai, X., Ritzau-Jost, A., Kramer, P.F., Li, Y., Khaliq, Z.M., Hallermann, S. & Kaeser P.S. # (2022). An action potential initiation mechanism in distal axons for the control of dopamine release. Science, 375, 1378-1385.

Hasegawa, E., Miyasaka, A., Sakurai, K., Cherasse, Y., Li, Y., & Sakurai, T. # (2022). Rapid eye movement sleep is initiated by basolateral amygdala dopamine signaling in mice. Science, 375(6584), pp.994-1000.

Deng, H., Xiao, X., Yang, T., …, Li, Y., Huang, J. & Li, B. #. (2021) A genetically defined insula-brainstem circuit selectively controls motivational vigor. Cell, 184, 6344-6360.

Wang, J.#, Li, J.#, Yang, Q.#, Xie, Y.-K., Wen, Y.-L., Xu, Z.-Z., Li, Y., Xu, T., Wu, Z.-Y., Duan, S., & Xu, H.* (2021). Basal forebrain mediates prosocial behavior via disinhibition of midbrain dopamine neurons. Proceedings of the National Academy of Sciences,118(7), e2019295118. https://doi.org/10.1073/pnas.2019295118.

Kim, H. R.*, Malik, A. N., Mikhael, J. G., Bech, P., Tsutsui-Kimura, I., Sun, F., Zhang, Y., Li, Y., Watabe-Uchida, M., Gershman, S. J., & Uchida, N.* (2020). A Unified Framework for Dopamine Signals across Timescales. Cell, https://doi.org/https://doi.org/10.1016/j.cell.2020.11.013.

Peng, W.#, Wu, Z.#, Kun, S.#, Zhang, S., Li, Y. & Min, X.* (2020). Regulation of sleep homeostasis mediator adenosine by basal forebrain glutamatergic neurons. Science, 369, 1208.

Mazzone, C.M., Liang-Guallpa, J.,Li, C., Wolcott, N. S., Boone, M. H., Southern, M., Kobzar, N. P., Salgado, I. A., Reddy, D. M., Sun, F., Zhang, Y., Li, Y., Cui, G. * & Krashes, M. J.* (2020). High-fat food biases hypothalamic and mesolimbic expression of consummatory drives. Nature Neuroscience, https://doi.org/10.1038/s41593-020-0684-9.

Lin, R., Liang, J., Wang, R., Yan, T., Zhou, Y., Liu, Y., Feng, Q., Sun, F.,, Li, Y., Li, A., Gong, H., & Luo, M.* (2020). The Raphe Dopamine System Controls the Expression of Incentive Memory. Neuron, 1420-19.

Handler, A., Graham, T. G. M., Cohn, R., Morantte, I., Siliciano, A. F., Zeng J., Li, Y. & Ruta, V.* (2019). Distinct dopamine receptor pathways underlie the temporal sensitivity of associative learning. Cell, 178(1), 60-75.

Li, B.#, Wong, C.#, Gao, S. M., Zhang, R., Sun, R., Li, Y., & *Song, Y. (2018). The retromer complex safeguards against neural progenitor-derived tumorigenesis by regulating Notch receptor trafficking. eLife, 7, e38181.

Tanaka, M., Sun, F., Li, Y., & Mooney, R.* (2018). A mesocortical dopamine circuit enables the cultural transmission of vocal behaviour. Nature, 563(7729), 117-120.

Shen, Y., Ge, W. P., Li, Y., Hirano, A., Lee, H. Y., Rohlmann, A., Missler, M., Tsien, R. W., Jan, L. Y., Fu, Y. H.* & Ptacek, L. J.* (2015). Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis. Proceedings of the National Academy of Sciences, 112(10), 2935-2941.

Liang, L., Li, Y., Potter, C. J., Yizhar, O., Deisseroth, K., Tsien, R. W., & Luo, L.* (2013). GABAergic Projection Neurons Route Selective Olfactory Inputs to Specific Higher-Order Neurons. Neuron, 79(5), 917-931.

Park, H., Li, Y., & Tsien, R. W.* (2012). Influence of synaptic vesicle position on release probability and exocytotic fusion mode. Science, 335(6074), 1362-1366.

Yoo, A. S.*, Sun, A. X., Li, L., Shcheglovitov, A., Portmann, T., Li, Y., Lee-Messer, C., Dolmetsch, R. E., Tsien R. W. & Crabtree, G. R.* (2011). MicroRNA-mediated conversion of human fibroblasts to neurons. Nature, 476(7359), 228-231.

Zhang, Q., Li, Y., & Tsien, R. W.* (2009). The dynamic control of kiss-and-run and vesicular reuse probed with single nanoparticles. Science, 323(5920), 1448-1453.

Kuner, T.*, Li, Y., Gee, K. R., Bonewald, L. F., & Augustine, G. J. (2008). Photolysis of a caged peptide reveals rapid action of N-ethylmaleimide sensitive factor before neurotransmitter release. Proceedings of the National Academy of Sciences, 105(1), 347-352.

Reviews, Book Reviews and Highlights
Qian, T., Wang, H., Xia, X., & Li, Y.# (2023) Current and emerging methods for probing neuropeptide transmission. Current Opinion in Neurobiology, 81, 102751.

Dong, C.#, Zheng, Y.#, Long-Iyer, K., Wright, E. C., Li, Y.*, & Tian, L.* (2022). Fluorescence imaging of neural activity, neurochemical dynamics, and drug-specific receptor conformation with genetically encoded sensors. Annual Review of Neuroscience.

Wu, Z., Lin, D., & Li, Y.* (2022). Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators. Nature Reviews Neuroscience.

Zhuo, Y., Li, Y.* (2022). New imaging methods for monitoring dopaminergic neurotransmission. Science China Life Sciences, 65.

Yulong Li. (2021). Neuron, 109(21), 3346-3348.

Yu, H., Wangensteen, K., Deng, T., Li, Y., & Luo, W.* (2021). MRGPRX4 in Cholestatic Pruritus. Semin Liver Dis41(03), 358-367.

Wan, J. & Li, Y.* (2020). Recent Advances in Detection Methods for Neurotransmitters. Chinese Journal of Analytical Chemistry, 48(3), 307-315. (In Chinese)

Wu, Z.* & Li, Y.* (2020). New frontiers in probing the dynamics of purinergic transmitters in vivo. Neuroscience Research, https://doi.org/10.1016/j.neures.2020.01.008.

Zeng, J., Sun, F., Wan, J., Feng, J. & Li, Y.* (2019). New optical methods for detecting monoamine neuromodulators. Current Opinion in Biomedical Engineering, https://doi.org/10.1016/j.cobme.2019.09.010.

Jing, M., Zhang, Y., Wang, H. & Li, Y.* (2019). GPCR‐based sensors for imaging neurochemicals with high sensitivity and specificity. Journal of Neurochemistry, https://doi.org/10.1111/jnc.14855.

Dong, A.*, Liu, S., & Li, Y.* (2018). Gap Junctions in the Nervous System: Probing Functional Connections Using New Imaging Approaches. Frontiers in Cellular Neuroscience, 12, 320.

Wang, H., Jing, M., & Li, Y.* (2018). Lighting up the brain: genetically encoded fluorescent sensors for imaging neurotransmitters and neuromodulators. Current Opinion in Neurobiology, 50, 171-178.

Wang, A.#, Feng, J.#, Li, Y.*, & Zou, P.* (2018). Beyond Fluorescent Proteins: Hybrid and Bioluminescent Indicators for Imaging Neural Activities. ACS chemical neuroscience, 9(4), 639-650.

Qian, C., & Li, Y.* (2015). Spine maturation and pruning during development: Cadherin/Catenin complexes come to help. Science China. Life sciences,58(9), 929.

Li, Y.*, & Rao, Y.* (2015). Pied Piper of Neuroscience. Cell, 163(2), 267-268.

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