Dr. Bailong Xiao
Email：xbailong@mail.tsinghua.edu.cn
Tel：＋86-10－62773981
Research Interests:
Many fundamental biological processes such as the sense of touch and pain and the regulation of vascular development and blood pressure require designated mechanotransducers for converting mechanical force into electrochemical signals, a process termed mechanotransduction. Mechanically activated (MA) cation channels represent a specialized type of mechanotransducers for rapidly responding to changes of mechanical force to either excite cell membranes or trigger biochemical signaling. However, the molecular identities and mechanogating mechanisms of mammalian MA cation channels remain largely unknown, which has rendered mechanotransduction much less understood compared to our understanding of chemotransduction and electrotransduction, the other two types of biological signal transduction mechanisms. Following the discovery and establishment of the MA Piezo channel family, we have been utilizing Piezo channels as prototypes of mammalian MA cation channels to understand how Piezo channels effectively convert mechanical force into selective cation permeation at an atomic-level of spatial resolution, a millisecond-level of temporal resolution, a picoampere-level of current resolution and a piconewton level of force resolution, and how their mechanosensitivity and ion permeation properties precisely control various mechanotransduction processes at cellular and animal levels. Our ultimate goal is to harness the deep understanding of Piezo channels for developing novel therapeutics for disease treatment or novel technologies for biological manipulation. We are also interested in identifying novel MA channels via adopting an innovative structural and pharmacological profiling approach.The proposed studies might not only advance our understanding of MA ion channels and the mechanotransduction mechanism, but also help to reveal novel therapeutic targets for treating devastating diseases such as pain, hypertension, cancer and bone loss.
Selected publications (*first author, #corresponding author):
1. Jie Geng*, Wenhao Liu*, Heng Zhou*, Tingxin Zhang1*, Li Wang1*, 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. Epub 2020 Mar 5.
2. 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. Epub 2019 Aug 27.
3. 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 ahead of print] (Featured by Nature News & Views).
4. 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.
5. 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.
6. 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. [Epub ahead of print]
7. 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. Review.
8. 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.)
9. 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.
10. 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. (#Corresponding author).
11. 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.
12. 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.
13. 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)
14. 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. Nov 5;527(7576):64-9. (#Co-corresponding author).
15. 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; Selected by Faculty of 1000; Featured by Nature News & Views; TSRI News & Views; Reported by Science Daily)
16. Bailong Xiao*, Bertrand Coste, Jayanti Mathur, Ardem Patapoutian (2011). Temperature-dependent STIM1 activation induces Ca2+ 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)
17. Bailong Xiao*, Ardem Patapoutian (2011). Scratching the surface: a role of pain-sensing TRPA1 in itch. Nat Neurosci. 2011 May;14(5):540-2. PMID: 21522144 News & Views
18. Bailong Xiao*, Adrienne E. Dubin, Badry Bursulaya, Veena Viswanath, Timothy J. Jegla, Ardem Patapoutian (2008). Identification of Transmembrane Domain Five as a Critical Molecular Determinant of Menthol Sensitivity in Mammalian TRPA1 Channels. J Neurosci. 2008 Sep 24;28(39):9640-51.
19. Lindsey J. Macpherson (co-first), Bailong Xiao (co-first), Kelvin Y. Kwan (co-first), Matt J. Petrus, Adrienne E. Dubin, SunWook Hwang, Benjamin Cravatt, David P. Corey, Ardem Patapoutian (2007). An Ion Channel Essential for Sensing Chemical Damage. J Neurosci. 2007 Oct 17;27(42):11412-5.
20. Bailong Xiao*, Xixi Tian, Wenjun Xie, Peter P. Jones, Shitian Cai, Xianhua Wang, Dawei Jiang, Lin Zhang, Keyun Chen, Michael P. Walsh, Heping Cheng, and S. R. Wayne Chen (2007). Functional Consequence of PKA-dependent Phosphorylation of the Cardiac Ryanodine Receptor: Sensitization of Store-overload-induced Ca2+ release (SOICR). J Biol Chem. 2007 Aug 10.
21. Bailong Xiao*, Guofeng Zhong, Masakazu Obayashi, Dongmei Yang, Michael P. Walsh, Yakhin Shimoni, Heping Cheng, Henk ter Keurs, and S. R. Wayne Chen (2006). Serine-2030, but not Serine-2808, is the Major RyR2 Phosphorylation Site Responding to PKA Activation upon beta-adrenergic Stimulation in Normal and Failing Hearts. Biochem J. 2006 Feb 17. (Commented by editorial)
22. Bailong Xiao*, Ming Tao Jiang, Mingcai Zhao, Dongmei Yang, Cindy Sutherland, F. Anthony Lai, Michael P. Walsh, Heping Cheng, David C. Warltier, and S. R. Wayne Chen (2005). Characterization of a Novel Protein Kinase A Phosphorylation Site, Serine-2030, Reveals No PKA Hyperphosphorylation of the Cardiac Ryanodine Receptor in Canine Heart Failure. Circ Res. 2005 Apr 29;96(8):847-55.
23. Bailong Xiao*, Cindy Sutherland, Michael P. Walsh, S. R. Wayne Chen (2004). Protein Kinase A Phosphorylation at Serine-2808 of the Cardiac Ca2+-Release Channel (Ryanodine Receptor) Does Not Dissociate 12.6-kDa FK506-Binding Protein (FKBP12.6). Circ Res. 2004 Mar 5;94(4):487-95.
24. Bailong Xiao*, Haruko Masumiya, Dawei Jiang, Ruiwu Wang, Yoshitatsu Sei, Lin Zhang, Takashi Murayama, Yasuo Ogawa, F. Anthony Lai, Terence Wagenknecht, and S. R. Wayne Chen (2002). Isoform Dependent Formation of Heteromeric Ca2+ Release Channels (Ryanodine Receptors). J Biol Chem. 2002 Nov 1; 277(44): 41778-85. (Selected by Faculty of 1000)