Name

Jie Xu

Title

Investigator

Degree

Ph.D.

Subject

Molecular Medicine

Position

Investigator

Phone

x1211

E-mail

xujie56@mail.sysu.edu.cn

□ Master Supervisor

• Doctoral Supervisor

Research Interest

Dr. Xu’s group is working on investigating the role of blood flow sensor GPR68 in ischemic diseases, aiming to improve patient outcome via accelerating collateral circulation, by mimicking the effect of blood flow using small molecules modulation GPR68. He is also working on how mechanical properties of extracellular matrix (stiffness, tension) influence the fibrosis process and has gained considerable insights by using tunable synthetic matrices. Lastly, his group recently established the first 384-well format high-throughput mechanical stretch

Biography

Dr. Xu is a principal investigator in the Institute of Precision Medicine (IPM) at the 1^st Affiliated Hospital. He received his postdoctoral training with Nobel Prize Laureate Dr. Ardem Patapoutian at Howard Hughes Medical Institute, Scripps Research Institute, studying mechanotransduction, i.e., how cells convert physical force into biological signals. Collaborating with Novartis, as well as Dr. Shu Chien at UCSD, Dr. Xu developed the world’s first high-throughput fluid shear stress screening device. Using this innovative system, he successfully discovered GPR68 as a mechanosensitive GPCR that senses the frictional force generated by blood flow and regulates the pathophysiology of blood vessels in response to changes in blood flow rate (Cell, 2018). In addition, Dr. Xu and colleagues characterized the physiological functions of mechanically-sensitive ion channel Piezo1 in the context of vasculature development (PNAS, 2014). Dr. Xu was also the champion of a 2.3-million compound screen resulting in a novel Piezo1 agonist Yoda1 (eLife 2015).

After postdoc, Dr. Xu’s became a Principal Investigator at Novartis and his group focused on translating the discovery of novel GPR68 biology into therapies for vascular diseases through high-throughput screening and preclinical genetic models. Additionally, his group is also at the cutting edge of next generation of phenotypic screens using 3D hydrogel as matrix to reinvent the way of assaying hepatic stellate cell (HSC) and cardiac fibroblast activation in vitro (Hep Comm 2019). stimulation system and is in the forefront of hunting for novel sensor of mechanical force.

Publications

Eloy D Hernandez, Lianxing Zheng, Young Kim, Bin Fang, Bo Liu, Reginald A Valdez, William F Dietrich, Paul V Rucker, Donatella Chianelli, James Schmeits, Dingjiu Bao, Jocelyn Zoll, Claire Dubois, Glenn C Federe, Lihao Chen, Sean B Joseph, Lloyd B Klickstein, John Walker, Valentina Molteni, Peter McNamara, Shelly Meeusen, David C Tully, Michael K. Badman, Jie Xu*, Bryan Laffitte. Tropifexor‐mediated abrogation of steatohepatitis and fibrosis is associated with the antioxidative gene expression profile in rodents, Hepatology Communications, 2019, 3(8): 1085-1097.

Scott Hammack, Bryan Laffitte, Ardem Patatpoutian, Jie Xu; Modulators of GPR68 and Uses Thereof for Treating and Preventing Diseases, World Intellectual Property Organization, WO 2019/150309 A1 (2019)

Jie Xu, Jayanti Mathur, Emilie Vessières, Scott Hammack, Keiko Nonomura, Julie Favre, Linda Grimaud, Matt Petrus, Allain Francisco, Jingyuan Li, Van Lee, Fu-li Xiang, James K. Mainquist, Stuart M. Cahalan, Anthony P. Orth, John R. Walker, Shang Ma, Viktor Lukacs, Laura Bordone, Michael Bandell, Bryan Laffitte, Yan Xu, Shu Chien, Daniel Henrion and Ardem Patapoutian. GPR68 senses flow and is essential for vascular physiology. Cell 173 (3): 762-775 (2018)

Ruhma Syeda, Jie Xu, Adrienne E. Dubin, Bertrand Coste, Jayanti Mathur, Truc Huynh, Jason Matzen, Jianmin Lao, David C. Tully, Ingo H. Engels, H. Michael Petrassi, Andrew M. Schumacher, Mauricio Montal, Michael Bandell, Ardem Patapoutian. Chemical activation of the mechanotransduction channel Piezo1. eLife (2015;4:e07369)

Sanjeev S. Ranade, Zhaozhu Qiu, Seung-Hyun Woo, Sung Sik Hur, Swetha E. Murthy, Stuart M. Cahalan, Jie Xu, Jayanti Mathur, Michael Bandell, Bertrand Coste, Yi-Shuan J. Li, Shu Chien, Ardem Patapoutian. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proceedings of the National Academy of Sciences, 111(28), 10347-10352 (2014).

Jie Xu, Mo Li, Ping Shen. A G-Protein-Coupled Neuropeptide Y-Like Receptor Suppresses Behavioral and Sensory Response to Multiple Stressful Stimuli in Drosophila. Journal of Neuroscience, 30(7):2504-2512 (2010).

Jie Xu, Andrew T. Sornborger, Jennifer K. Lee and Ping Shen. Drosophila TRPA channel modulates sugar-stimulated neuronal excitation, avoidance and social response. Nature Neuroscience, 11, 676-682 (2008).

Qi Wu, Yan Zhang, Jie Xu and Ping Shen. Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proceedings of the National Academy of Sciences, 102, 13289-13294 (2005)

Projects                        

2020 NSFC (82070311)

Honors and Awards

2012 Novartis Special Contribution Award

2018 Academy of Cardiovascular Research Excellence Junior Faculty Award