Faculty | Bailong XIAO, Ph.D.

Bailong XIAO, PI

Principal Investigator, Tenured Associate Professor

Professor Xiao obtained his B.S. from the Sun Yat-sen University in 2001, and then pursued his PhD study with Dr. Wayne Chen from the University of Calgary in Canada from 2001 to 2006, focusing on studying the structure-function relationships and physiological roles of the cardiac Ryanodine Receptor. Then he did his postdoctoral training with Dr. Ardem Patapoutian at the Scripps Research Institute in the United States from 2007 to 2012, focusing on studying the molecular and cellular mechanisms that underly the sensation of touch and pain. In 2013, he was appointed as a Tenure-track assistant professor in Tsinghua University, and then promoted as a tenured associate professor in 2018.

 

Research Interests

Ion channels are fundamental membrane proteins that regulate the flow of ions across cell membranes and control cell excitability and function. Inappropriate channel activities caused by either mutations or abnormal physiological regulations underlie the etiology of numerous pathologies (collectively known as channelopathies). Ion channels are also the second largest family of targets for clinically used drugs. Thus, ion channels represent a major research topic in the field of neuroscience, physiology and pharmacology.
 
Dr. Bailong Xiao’s laboratory has been interested in identifying and characterizing the so-called sensory ion channels, including the temperature-activated ion channels such as the STIM1/Orai-constituted CRAC channels and the mechanically activated ion channels such as the Piezo channels. These channels can function as molecular receptors for various physical stimuli including temperature, chemicals, and mechanical force, and consequently govern the sense of touch and other mechanotransduction processes. By focusing on these ion channels, we aim to better understand the molecular and cellular mechanisms of the sense of touch and pain and mechanotransduction in other biological systems. Our ultimate goal is to develop novel therapeutics by targeting these ion channels.
 
Taking a multidisciplinary approach combining protein engineering and purification, cryo-EM, electrophysiology, drug screening and mouse genetics, we aim to 1) understand how the mechanosensitive Piezo channels serves as effective mechanotransducers for converting mechanical force into cationic conduction at both the molecular and physiological levels; 2) identify novel mechanosensitive or thermosensitive ion channels/receptors.
 
Major scientific contributions
Dr. Bailong Xiao has contributed to the identification and characterization of several classes of ion channels involved in sensing noxious chemicals, temperature and mechanical force (J Neurosci. 2007; Nat Chem Biol. 2011; Nature 2012; Cell Research 2019), including the long-sought-after mammalian mechanosensitive cation channels – Piezo channels, which represent a novel and unique class of channel proteins. Aiming to understand how the mechanosensitive Piezo channels serve as effective mechanotransducers for converting mechanical force into cationic conduction at both the molecular and physiological levels, he has made significant contribution in exploring their structure-function relationships (Nature 2015, 2018; Neuron 2016, 2017; Nat Commun. 2017, 2018; Cell Reports 2019; Annual Review of Pharmacology and Toxicology 2020). His ultimate goal is to harness the deep understanding of the Piezo channels for developing novel therapeutics and technologies for disease treatment or biological manipulation.
The cryo-EM structure and a lever-like mechanogating mechanism of the mechanosensitive Piezo1 channel. A, The three-bladed, propeller-like cryo-EM structure of Piezo1. B and C, The 38-TM topology model (B) and cartoon model (C) showing the featured structural domains and critical functional sites. The characteristically curved Blade consisting of 9 Repetitive THUs, the 90 Å-long intracellular Beam and the Anchor domains form the peripheral mechanotransduction module, while the last two-TM containing C-terminal domain of ~350 residues form the pore module. D, The ion-conducting pore module shown in Ribbon diagram or in surface electrostatic potential. We propose that Piezo1 employs its blades and the long beams with the L1342/L2345 as a pivot to form a lever-like apparatus. Such a lever-like mechanotransduction mechanism might enable Piezo channels to effectively convert a large conformational change of the distal blades to a relatively slight opening of the central pore, allowing cation-selective permeation. Three sets of such lever-like apparatus are further assembled into a gigantic propeller-like machinery, which might confer a coordinated mechanosensitivity.
 
1. Revealed the physiological roles of Piezo channels in mediating gentle touch, proprioception and suppressing acute pain responses in mice (Cell reports 2019)
2. Determined the high-resolution cryo-EM structure of the Piezo1 channel and functionally revealed its lever-like mechanogating mechanism (Nature 2018).
3. Identified Piezo1 chemical activators and revealed the underlying activation mechanism (Nat Commun. 2018).
4. Identified SERCAs as inhibitory interacting proteins of Piezo channels via acting on the 14-residue-constituted intracellular linker that connects the N-terminal mechanotransduction module and the C-terminal pore module (Nat Commun. 2017).
5. Uncovered the bona fide ion-conducting pore module and mechanotransduction module of the mechanosensitive Piezo channels (Neuron 2016).
6. Determined the cryo-EM structure of the mammalian mechanosensitive Piezo1 ion channel (Nature 2015).
7. Established Piezo proteins as the pore-forming subunits of the mammalian mechanically activated cation channels (Nature 2012).
8. Discovered STIM1 as an in vivo warm sensor in skin keratinocytes and proposed a peripheral reference temperature mechanism for precise warm sensation in mice (Cell Research 2019; Nature Chemical Biology 2011)
 

Honors and Awards

The National Science Fund for Distinguished Young Scholar
The 10,000 Talent Program Scholar
The Young 1,000 Talent Program Scholar
Excellent Young Scientists Award
Bayer Investigator Fellowship and Janssen Investigator Fellowship in Tsinghua University
 

Selected Publications

1. Bailong Xiao# (2020) Levering mechanically activated Piezo channels for potential pharmacological intervention. Annual Review of Pharmacology and Toxicology (accepted).
2. 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.
3. 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]
4. 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. 2018 Nov 30. doi: 10.1111/febs.14711. 
5. 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.
6. 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 2018 Feb 22;554(7693):487-492 
7. Tingxin Zhang*, Shaopeng Chi1*, 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. 
8. Yubo Wang, Bailong Xiao# (2017). The mechanosensitive Piezo1 channel: structural features and molecular bases underlying its ion permeation and mechanotransduction. J Physiol. 2017 Nov 24. 
9. 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. 
10. 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. 
11. 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. 
12. 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. 
13. 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.