肖百龙 - 清华大学

个人简介

肖百龙博士于2001年从中山大学生命科学学院生物化学专业获得理学学士学位；2001-2006年在加拿大卡尔加里大学(University of Calgary)师从Wayne Chen教授获得心血管分子生物学方向博士学位；2007-2012年在美国斯克利普斯研究所(The Scripps Research Institute) 师从Ardem Patapoutian教授，从事神经科学博士后研究。现任清华大学药学院副院长，其自2013年起任职于清华大学药学院、清华－北大生命科学联合中心及IDG／麦戈文脑科学研究院，担任研究员和博士生导师，主持（过）国家杰出青年科学基金、国家优秀青年科学基金、重点项目、面上项目以及及国家重大研究计划等多项科研项目。过去20年一直致力于离子通道研究，以第一作者与通讯作者（含共同）身份在Nature（4篇Article），Neuron（3篇），Nature Neuroscience，Nature Chemical Biology，Nature Communications（3篇），Cell Research, Circulation Research (2篇)，Annual Review of Pharmacology and Toxicology, Trends in Biochemical Sciences等高水平期刊发表论文28篇，期中2篇被收录进神经生物学教科书。荣誉及获奖国家杰出青年科学基金获得者（2018）国家优秀青年科学基金获得者（2014）

研究领域

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、本体觉、内脏觉、血压调节、心脏搏动、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通道药物与技术；4）鉴定发现新型机械门控离子通道及其调控蛋白。

近期论文

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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. Online ahead of print. 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. 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. Jing Wang*, Jinghui Jiang*, Xuzhong Yang, Li Wang, Bailong Xiao# (2020) Tethering Piezo channels to the actin cytoskeleton for mechanogating via the E-cadherin-β-catenin mechanotransduction complex. bioRxiv preprint posted May 13, 2020. doi: https://doi.org/10.1101/2020.05.12.092148. 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). 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. 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). 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. 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. 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. 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. 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.) 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. 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. 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. 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. 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) 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. Bertrand Coste* (co-first), Bailong Xiao* (co-first), Jose S. Santos, Ruhma Syeda, Jorg Grandl, Kathryn S. Spencer, Sung Eun Kim, Manuela Schmidt, Jayanti Mathur, Adrienne E. Dubin, Mauricio Montal, Ardem Patapoutian (2012). Piezo Proteins Are Pore-forming Subunits of Mechanically Activated Channels. Nature. 2012 Feb 19;483(7388):176-81 PMID:22343900 ( Highly cited paper and this study has been cited by the textbook of Principals of Neurobiology edited by Dr. Liqun Luo; Selected by Faculty of 1000; Featured by Nature News & Views; TSRI News & Views; Reported by Science Daily) Bailong Xiao*, Bertrand Coste, Jayanti Mathur, Ardem Patapoutian (2011). Temperature-dependent STIM1 activation induces Ca 2+ influx and modulates gene expression. Nat Chem Biol. 2011 Jun;7(6):351-8. PMID: 21499266 ( Nominated for 2011 signaling breakthroughs of the year by Science Signaling; Featured by Nat Chem Biol. News & Views; Featured by TSRI News & Views; Reported by Science Daily)