肖百龙

电子邮件：xbailong@mail.tsinghua.edu.cn

电话：＋86-10－62773981

研究方向：

机械门控阳离子通道作为机械力分子受体承担将机械力刺激转化为生物电化学信号的功能，决定触觉、痛觉、血压调节、骨的生成与重塑等基本生命活动。但是由于这类通道在哺乳动物中的分子组成及机制长期未被了解，导致对其所介导的生物机械传感机制的研究和理解远落后于由配体或电压门控离子通道所介导的化学或电信号传感机制的理解。

进化上高度保守的Piezo通道家族是在哺乳动物中所鉴定发现并被确证的首类机械门控阳离子通道 (Coste B. et al., Science 2010; Coste B. and Xiao B. et al. Nature 2012)。我们综合利用生化结构、电生理膜片钳、高通量药物筛选、转基因小鼠模型以及人类遗传学等多学科研究手段，聚焦于从分子、细胞及动物水平解答Piezo通道如何将机械力刺激转化为电化学信号并决定其相关的生理病理功能这一核心科学问题，并致力于开发以Piezo通道为靶点的新型药物及技术。具体研究方向包括：1）从原子级别空间尺度、毫秒级别时间尺度、皮安级别电流尺度以及皮牛级别力学尺度，深入探究Piezo通道的动态机械门控机制以及调控机制；2）揭示Piezo 通道如何利用其生物物理特性决定其重要的生理病理功能；3）发现与开发Piezo通道药物；4）鉴定发现新型机械门控离子通道。

科研论文：

7. Bailong Xiao#  (2024) Mechanisms of mechanotransduction and physiological roles of PIEZO channels. Nature Reviews Molecular and Cell Biology 2024

Nov;25(11):886-903. doi: 10.1038/s41580-024-00773-5. Epub 2024 Sep 9.

8. Celeste M. Nelson, Bailong Xiao, Sara A. Wickström, Yves F. Dufrêne, Daniel J.

Cosgrove, Carl-Philipp Heisenberg, Sirio Dupont, Amy E. Shyer, Alan R. Rodrigues, Xavier Trepat, Alba Diz-Muñoz (2024) Mechanobiology: Shaping the future of cellular form and function. Cell, VOICES| VOLUME 187, ISSUE 11, P2652-2656, MAY 23,   2024. DOI:https://doi.org/10.1016/j.cell.2024.04.006

9. Shaopeng Chi*  Yaxiong Cui* , Haiping Wang* , Jinghui Jiang, Tingxin Zhang, Suhua Sun, Zhuan Zhou, Yi Zhong, Bailong Xiao#  (2022) Astrocytic Piezo1-mediated

mechanotransduction determines adult neurogenesis and cognitive functions.

Neuron. 2022 Sep 21;110(18):2984-2999.e8.  doi: 10.1016/j.neuron.2022.07.010. Epub 2022 Aug 12.

10.Xuzhong Yang* , Chao Lin* , Xudong Chen* , Shouqin Li* , Xueming Li# , Bailong Xiao# (2022) Deformation and curvature-gating of the PIEZO1 channel in lipid membranes. Nature 2022 Apr;604(7905):377-383. doi: 10.1038/s41586-022-04574-8. Epub 2022 Apr 6.

11.Jing Wang*, Jinghui Jiang*, Xuzhong Yang, Li Wang, Bailong Xiao#  (2022) Tethering Piezo channels to the actin cytoskeleton for mechanogating via the E-cadherin-β- catenin  mechanotransduction  complex.  Cell  Rep.  2022  Feb 8;38(6):110342. doi: 10.1016/j.celrep.2022.110342.

12. Wei-Zheng Zeng#    and   Bailong Xiao#   (2021)   Eukaryotic   Mechanosensitive   Ion Channels (book chapter). Nonclassical Ion Channels in the Nervous System，Edited by Xu Tian-le, Long-Jun Wu, ISBN 9780367623951, Published August 20, 2021 by CRC Press.

13. Yao Rong*, Jinghui Jiang*, Yiwei Gao*, Jianli Guo, Danfeng Song, Wenhao

Liu, Mingmin Zhang, Yan Zhao# , Bailong Xiao# , Zhenfeng Liu#  (2021) TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or

stretch-induced channel activities in cells. Elife. 2021 Aug 19;10:e71474. doi:

10.7554/eLife.71474.

14. Yang Jiang*, Xuzhong Yang*, Jinghui Jiang*, Bailong Xiao# (2021) Structural Designs and Mechanogating of the Mechanosensitive Piezo channels. Trends Biochem Sci.

2021 Feb 17:S0968-0004(21)00022-0. doi: 10.1016/j.tibs.2021.01.008.

15. Fan Jiang, Kunlun Yin, Kun Wu, Mingmin Zhang, Shiqiang Wang, Heping Cheng, Zhou Zhou, Bailong Xiao# (2021) The mechanosensitive Piezo1 channel mediates heart mechano-chemo   transduction.   Nature   Commun.   2021 Feb   8;12(1):869. doi: 10.1038/s41467-021-21178-4.

16. Jie Geng*, Wenhao Liu*, Heng Zhou*, Tingxin Zhang*, Li Wang*, Mingmin Zhang, Yiran Li, Bo Shen, Xueming Li# , Bailong Xiao#  (2020) A plug-and-latch mechanism for gating the mechanosensitive Piezo channel. Neuron. 2020 May 6;106(3):438- 451.e6.doi: 10.1016/j.neuron.2020.02.010 (Featured by Neuron Previews).

17. Bailong Xiao# (2020) Levering mechanically activated Piezo channels for potential pharmacological intervention. Annual Review of Pharmacology and Toxicology 2020 Jan 6;60:195-218. doi: 10.1146/annurev-pharmtox-010919-023703.

18. Li Wang* , Heng Zhou* , Mingmin Zhang* , Wenhao Liu* , Tuan Deng, Qiancheng Zhao, Yiran Li, Jianlin Lei, Xueming Li# , Bailong Xiao# (2019) Structure and mechanogating of the mammalian tactile channel PIEZO2. Nature (Article) 2019 Sep;573(7773):225-

229. doi: 10.1038/s41586-019-1505-8. Epub 2019 Aug 21. (Featured by Nature News & Views).

19.Weijia Sun* , Shaopeng Chi* , Yuheng Li, Shukuan Ling, Yingjun Tan, Youjia Xu, Fan Jiang, Jianwei Li, Caizhi Liu, Guohui Zhong, Dengchao Cao, Xiaoyan Jin, Dingsheng Zhao, Xingcheng  Gao, Zizhong  Liu,  Bailong  Xiao# ,  and  Yingxian  Li#   (2019) The mechanosensitive Piezo1 channel is required for bone formation. Elife. 2019 Jul 10;8. pii: e47454. doi: 10.7554/eLife.47454.

20. Mingmin  Zhang,  Yanfeng  Wang,  Jie  Geng, Shuqin  Zhou, Bailong  Xiao#   (2019) Mechanically Activated   Piezo   Channels   Mediate   Touch   and   Suppress   Acute Mechanical Pain Response in Mice. Cell Rep. 2019 Feb 5;26(6):1419-1431.e4. doi: 10.1016/j.celrep.2019.01.056.

21.Xiaoling Liu*, Haiping Wang*, Yan Jiang*, Qin Zheng*, Matt Petrus, Mingmin Zhang, Sisi Zheng, Christian Schmedt, Xinzhong Dong, Bailong  Xiao#    (2019) STIM1 thermosensitivity defines the optimal preference temperature for warm sensation in mice. Cell Res. 2019 Jan 3. doi: 10.1038/s41422-018-0129-0.

22.Qiancheng   Zhao*,    Heng   Zhou*,    Xueming   Li# ,    Bailong    Xiao#      (2018)   The mechanosensitive Piezo1 channel: a three-bladed propeller-like structure and a lever- like   mechanogating    mechanism.   FEBS   J.    2019   Jul;286(13):2461-2470.    doi: 10.1111/febs.14711. Epub 2018 Dec 14.

23.Qiancheng Zhao*, Heng Zhou*, Shaopeng Chi*, Yanfeng Wang*, Jianhua Wang, Jie Geng, Kun Wu, Wenhao Liu, Tingxin Zhang, Meng-Qiu Dong, Jiawei Wang, Xueming Li# , Bailong Xiao#   (2018) Structure and Mechanogating Mechanism of the Piezo1 Channel.      Nature (Article)       2018       Feb       22;554(7693):487-492.       doi: 10.1038/nature25743.  Epub  2018  Jan 22. (Featured by Nature News & Views; Selected by Faculty of 1000.) (Highly cited paper and this study has been cited by the textbook of Principals of Neurobiology edited by Dr. Liqun Luo)

24. Yanfeng Wang*, Shaopeng Chi*, Huifang Guo, Guang Li, Li Wang, Qiancheng Zhao, Yu Rao, Liansuo Zu, Wei He, Bailong Xiao#  (2018) A lever-like transduction pathway for  long-distance  chemical-  and  mechano-gating  of  the  mechanosensitive  Piezo1 channel. Nat Commun. 2018 Apr 3;9(1):1300. doi: 10.1038/s41467-018-03570-9.

25. Yubo Wang, Bailong Xiao# (2018). The mechanosensitive Piezo1 channel: structural features and molecular bases underlying its ion permeation and mechanotransduction. J Physiol. 2018 Mar 15;596(6):969-978.

26. Tingxin Zhang*, Shaopeng Chi*, Fan Jiang, Qiancheng Zhao, Bailong Xiao#  (2017). A protein interaction mechanism for suppressing the mechanosensitive Piezo channels. Nat Commun. 2017 Nov 27;8(1):1797.

27. Jie Geng*, Qiancheng Zhao*, Tingxing Zhang*, Bailong Xiao# (2017). In Touch With the    Mechanosensitive     Piezo     Channels:     Structure,     Ion     Permeation    and Mechanotransduction. Curr Top Membr. 2017;79:159-195.

28. Qiancheng Zhao*, Kun Wu*, Jie Geng*, Shaopeng Chi*, Yanfeng Wang, Peng Zhi, Mingmin Zhang,  Bailong Xiao#   (2016).  Ion  Permeation  and  Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels. Neuron. 2016 Mar 16;89(6):1248-

63. (Previewed by Neuron; Reported by www.Eurekalert.org)

29. Jingpeng Ge*, Wanqiu Li*, Qiancheng Zhao*, Ningning Li*, Maofei Chen, Peng Zhi, Ruochong Li, Ning Gao# , Bailong Xiao# , Maojun Yang# (2015). Architecture of the mammalian mechanosensitive Piezo1 channel. Nature (Article). Nov 5;527(7576):64- 9. (Highly cited paper).

30. Zhang J, Li J, Hou Y, Lin Y, Zhao H, Shi Y, Chen K, Nian C, Tang J, Pan L, Xing Y, Gao H, Yang B, Song Z, Cheng Y, Liu Y, Sun M, Linghu Y, Li J, Huang H, Lai Z, Zhou Z, Li Z, Sun X, Chen Q, Su D, Li W, Peng Z, Liu P, Chen W, Huang H, Chen Y, Bailong Xiao, Ye  L,  Chen  L,  Zhou  D. Osr2  functions  as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor. Cell 2024 Jun 20;187(13):3409-3426.e24. doi: 10.1016/j.cell.2024.04.023. Epub 2024 May 13.

31. Liang Guo , Qionglei Mao, Ji He, Xiaoling Liu , Xuejiao Piao , Li Luo , Xiaoxu Hao, Hanzhi Yu, Qiang Song, Bailong Xiao, Dongsheng Fan, Zhaobing Gao, Yichang Jia

(2023) Disruption of ER ion homeostasis maintained by an ER anion channel CLCC1 contributes   to   ALS-like    pathologies.   Cell Res    2023   Jul;33(7):497-515.    doi: 10.1038/s41422-023-00798-z. Epub 2023 May 4.

32. Jie Li, Shuang Liu, Chenmeng Song, Qun Hu, Zhikai Zhao, Tuantuan Deng, Yi

Wang, Tong Zhu, Linzhi Zou, Shufeng Wang, Jiaofeng Chen, Lian Liu, Hanqing

Hou, Kexin Yuan, Hairong Zheng, Zhiyong Liu, Xiaowei Chen, Wenzhi Sun, Bailong Xiao, Wei Xiong (2021) PIEZO2 mediates ultrasonic hearing via cochlear outer hair cells in mice. Proc Natl Acad Sci U S A. 2021 Jul 13;118(28):e2101207118.

33. Longwei Liu, Hongsheng Yu, Hui Zhao, Zhaozhao Wu, Yi Long, Jingbo Zhang,

Xiaojun Yan, Zhifeng You, Lyu Zhou, Tie Xia, Yan Shi, Bailong Xiao, Yingxiao

Wang, Chenyu Huang, Yanan Du (2020) Matrix-transmitted paratensile signaling

enables myofibroblast-fibroblast cross talk in fibrosis expansion. Proc Natl Acad Sci U S A. 2020 May 19;117(20):10832-10838.

34. David Beech, Bailong Xiao (2018). Piezo channel mechanisms in health and disease. J Physiol. 2018 Mar 15;596(6):965-967.

35. Pan X, Li Z, Zhou Q, Shen H, Wu K, Huang X, Chen J, Zhang J, Zhu X, Lei J, Xiong W, Gong H, Bailong Xiao, Yan N (2018). Structure of the human voltage-gated sodium channel  Nav1.4  in  complex with β1. Science. 2018 Sep 6. pii: eaau2486. doi: 10.1126/science.aau2486.

36. Zhang Y, Rong H, Zhang FX, Wu K, Mu L, Meng J, Bailong Xiao, Zamponi GW, Shi Y (2018). A  Membrane  Potential- and Calpain-Dependent  Reversal of Caspase-1 Inhibition   Regulates   Canonical   NLRP3    Inflammasome.   Cell   Rep.   2018   Aug 28;24(9):2356-2369.e5. doi: 10.1016/j.celrep.2018.07.098.

37. Si Wang, Boqiang Hu, Zhichao Ding, Yujiao Dang, Jun Wu, Di Li, Xiaoling Liu, Bailong Xiao, Weiqi Zhang, Ruotong Ren, Jinghui Lei, Huifang Hu, Chang Chen, Piu Chan, Dong Li, Jing Qu, Fuchou Tang, and Guang-Hui Liu (2018) ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells. Cell Discov. 2018;

4: 2.

38. Lan H, Wu K, Zheng Y, Pan M, Huang YC, Gao S, Zheng QY, Zheng JS, Li YM, Xiao B, Liu L (2016). Total synthesis of mambalgin-1/2/3 by two-segment hydrazide-based native chemical ligation. J Pept Sci. 2016 May;22(5):320-6.