Research | Bailong XIAO, Ph.D.

Bailong XIAO

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 cardiac Ryanodine Receptor. Then he did his postdoctoral training in the filed of somatosensory neurobiology at the Scripps Research Institute in the United States with Dr. Ardem Patapoutian from 2007 to 2012. In 2013, he was appointed as a Tenure-Track assistant professor in Tsinghua University, and then promoted as a Tenure-Track associate professor in 2015.

 

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). Thus, an understanding of their structure and function is likely to lead to the development of novel therapeutics.
 
My laboratory is interested in identifying and characterizing the so-called sensory ion channels, including temperature-activated ion channels and mechanically activated ion channels such as Piezo channels. These channels can function as 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.
 
Our current research focuses aim to 1) comprehensively characterize the newly identified mechanically activated Piezo channels; 2) unravel the physiological relevance of the thermosensitive STIM1/Orai-mediated CRAC channels; 3) identify novel mechanosensitive or thermosensitive ion channels/receptors.

Selected Achievements

1.Uncovered the ion permeation and mechanotransduction mechanisms of the mechanosensitive Piezo channels (Zhao et al., Neuron 2016; Previewed by Neuron).

2.Determined the cryo-EM structure of the mammalian mechanosensitive Piezo1 ion channel (Ge et al., Nature 2015).

3.Established Piezo proteins as the pore-forming subunits of mammalian mechanically activated cation channels (Coste and Xiao et al., Nature 2012, highly cited paper).

4.Identified STIM1/Orai1 as a novel class of temperature-activated ion channels (Xiao et al., Nat Chem Biol. 2011, Nominated for 2011 signaling breakthroughs of the year by Science Signaling).

Honors and Awards

Excellent Young Scientists Award, Bayer Investigator Fellowship and Janssen Investigator Fellowship in Tsinghua University

Selected Publications

1.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; Highlighted by Neuroscience Bulletin; News report by EurekAlert).
2.Jingpeng Ge (co-first), Wanqiu Li (co-first), Qiancheng Zhao (co-first), Ningning Li (co-first), Maofei Chen, Peng Zhi, Ruochong Li, Ning Gao#, Bailong Xiao#, Maojun Yang# (2015). Architecture of the mammalian mechanosensitive Piezo1 channel. Nature. 2015 Nov 5;527(7576):64-9. doi: 10.1038/nature15247. Epub 2015 Sep 21. (# Co-corresponding author).
3.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)
4.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)
5.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
6.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.
7.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.
8.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.
9.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)
10.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.
11.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.
12.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)
13.Adrienne E. Dubin, Manuela Schmidt, Jayanti Mathur, Matt J. PetrusBailong Xiao, Bertrand Coste, Ardem Patapoutian. Inflammatory signals enhance piezo2-mediated mechanosensitive currents. Cell Rep. 2012 Sep 27;2(3):511-7.Epub 2012 Aug 23. PMID: 22921401
14.Peter P. Jones, Xing Meng, Bailong Xiao, Shitian Cai, Jeff Bolstad, Terence Wagenknecht, Zheng Liu and S. R. Wayne Chen (2008). Localization of PKA phosphorylation site, Ser2030, in the three-dimensional structure of cardiac ryanodine receptor. Biochem J. 2008 Mar 1;410(2):261-70.
15.Xing Meng, Bailong Xiao, Shitian Cai, Xiaojun Huang, Fei Li, Jeff Bolstad, Ramon Trujillo, Judith Airey, S. R. Wayne Chen, Terence Wagenknecht, and Zheng Liu (2007). Three-Dimensional Localization of Serine 2808, a Phosphorylation Site in Cardiac Ryanodine ReceptorJ Biol Chem. 2007 Aug 31;282(35):25929-39.
16.Dongmei Yang, Wei-Zhong Zhu, Bailong Xiao, Didier X. P. Brochet, S. R. Wayne Chen, Edward G. Lakatta, Rui-Ping Xiao and Heping Cheng (2007). Ca2+/calmodulin kinase II-dependent Phosphorylation of Ryanodine Receptors Suppresses Ca2+ Sparks and Ca2+ Waves in Cardiac Myocytes. Circ Res. 2007 Feb 16;100(3):399-407.
17.Masakazu Obayashi, Bailong Xiao, Bruno D. Stuyvers, Allen W. Davidoff, Jie Mei, S.R. Wayne Chen, Henk E.D.J. ter Keurs (2006). Spontaneous diastolic contractions and phosphorylation of the cardiac ryanodine receptor at serine-2808 in congestive heart failure in rat. Cardiovasc Res. 2006 Jan;69(1):140-51.
18.Dawei Jiang, Ruiwu Wang, Bailong Xiao, Huihui Kong, Philip Choi, Lin Zhang, and S. R. Wayne Chen (2005). Enhanced Store Overload Induced Ca2+ Release (SOICR) and Channel Sensitivity to Luminal Ca2+ Activation is a Common Defect of RyR2 Mutations Linked to Ventricular Tachycardia and Sudden Death. Circ Res. 2005 Nov 25;97(11):1173-81. (Commented by editorial)
19.Dawei Jiang, Bailong Xiao, Dongmei Yang, Ruiwu Wang, Philip Choi, Lin Zhang, Heping Cheng, and S. R. Wayne Chen  (2004). Ryanodine Receptor Mutations Associated with Ventricular Tachycardia and Sudden Cardiac Death Reduce the Threshold for Store Overload Induced Ca2+ Release (SOICR). Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):13062-7.
20.Dawei Jiang, Bailong Xiao, Xiaoli Li, and S. R. Wayne Chen (2003). Smooth Muscle Tissues Express a Major Dominant-Negative Splice Variant of the Type 3 Ca2+ Release Channel (Ryanodine Receptor) J Biol Chem. 2003 Feb 14; 278(7): 4763-9. (Selected by Faculty of 1000)
21.Haruko Masumiya, Ruiwu Wang, Jing Zhang, Bailong Xiao, S. R. Wayne Chen (2003) Localization of the 12.6-kDa FK506-binding protein (FKBP12.6) binding site to the NH2-terminal domain of the cardiac Ca2+ release channel (ryanodine receptor). J Biol Chem. 2003 Feb 7; 278(6): 3786-92.
22.Dawei Jiang, Bailong Xiao, Lin Zhang, S. R. Wayne Chen (2002). Enhanced Basal Activity of a Cardiac Ca2+ Release Channel (Ryanodine Receptor) Mutant Associated With Ventricular Tachycardia and Sudden Death. Circ Res. 9; 91(3): 218-25. (Commented by editorial)