Research

The overall research goal of Li’s lab is to determine how prion-like proteins, such as TIA1/TIAL, TDP-43, APP, and FUS, involve in various brain disorders and neurodegenerative diseases and help drug discovery based on their function and structure information. Prions are proteins that exist in two conformations: soluble and aggregated. The aggregated form is self-perpetuating. Initially discovered by Dr. Stanley Prusiner in the context of infectious diseases, prion-like conformation changes have also been found in several other neurodegenerative diseases, including Alzheimer’s, ALS, Huntington’s, Parkinson’s and Multiple sclerosis. Many of these prion-like proteins are related to RNA/DNA regulation and affect synaptic plasticity and brain circuitry. The lab is particularly interested in: 1) How these functional prion-like proteins are modulated by post-translational modification and chaperons; 2) How these proteins response to various stimuli (such as synaptic input, ROS, stress) and change synapse and circuitry through regulating downstream targets (mRNAs and genome). The lab is addressing these questions using a combination of molecular, genetic, electrophysiological, imaging, mouse behavior and structure biological methods.

Biography

2016-Present, Principal Investigator, SIAT, CAS
2008-2016, Postdoc Fellow/Associate Research Scientist, HHMI/Columbia University
2007, Ph.D., Case Western Reserve University
2002, M.S., Zhejiang University
1999, B.S., Zhejiang University

Selected publications

1. Qian ZJ, Li YJ, Chen JD, Li X, Gou DM. MiR-4632 mediates PDGF-BB-induced proliferation and antiapoptosis of plumonary artery smooth muscle cells via targting cJUN.American journal of physiology. Cell physiology313,C380-C391(2017)
2. Ben Ovryn, Xiang Li, Hille Chiel, Stefan Herlitze. Optical control of a rhodopsin-based switch. Proceeding of International Society of Optical Engineering, 2004, 5324, 197-207.
3. Xiang Li, Alexander Hümmer, Jing Han, Mian Xie, Katya Melnik-Martinez, Rosa L. Moreno, Matthias Buck, Melanie D. Mark, and Stefan Herlitze. G protein beta2 subunit-derived peptides for inhibiton and induction of G protein pathways. The Journal of Biological Chemistry, 2005, 280, 23945-23959
4. Xiang Li, Davina V. Gutierrez , M. Gartz Hanson , Jing Han , Melanie D. Mark , Hillel Chiel , Peter Hegemann , Lynn T. Landmesser, and Stefan Herlitze. Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc. Natl. Acad. Sci. USA, 2005, 102, 17816-17821
5. Jing Han, Melanie D. Mark, Xiang Li, Mian Xie, Sayumi Waka, Jens Rettig and Stefan Herlitze. RGS2 Determines Short-Term Synaptic Plasticity in Hippocampal Neurons by Regulating G(i/o)- Mediated Inhibition of Presynaptic Ca(2+) Channels. Neuron, 2006, 51(5):575-586
6. Blaine N. Armbruster, Xiang Li, Mark H. Pausch, Stefan Herlitze, and Bryan L. Roth. Evolving the lock to fit the key: using directed molecular evolution to create a family of muscarinic acetylcholine receptors potently activated by an inert ligand. Proc. Natl. Acad. Sci. U S A. 2007 Mar 20; 104(12):5163-8
7. Mian Xie, Xiang Li, Jing Han, Daniel L. Vogt, Silke Wittemann, Melanie D. Mark, and Stefan Herlitze Facilitation versus depression in cultured hippocampal neurons determined by targeting of Ca2+ channel Cav{beta}4 versus Cav{beta}2 subunits to synaptic terminals. Journal of Cell Biology 2007 Jul 30;178(3):489-502
8. Xiaobing Chen, Christine Winters, Rita Azzam, Xiang Li, James Galbraith, Richard D. Leapman, Thomas S. Reese. Organization of the core structure of the postsynaptic density. Proc. Natl. Acad. Sci. U S A 2008 Mar 7
9. Yi-Ping Rong, Ademuyiwa S. Aromolaran, Geert Bultynck, Fei Zhong, Xiang Li, Karen McColl, Stefan Herlitze, Shigemi Matsuyama, H. Llewelyn Roderick, Martin D.Bootman, Gregory A. Mignery, Jan B Parys, Humbert De Smedt, Clark W Distelhorst. Targeting Bcl-2-IP3 receptor interaction to reverse Bcl-2's inhibition of apoptotic calcium signals. Molecular Cell 2008 Jul 25;31(2):255-65
10. Xiaobing Chen, Christine Winters, Rita Azzam, Xiang Li, James Galbraith, Richard D. Leapman, Thomas S. Reese. Identifying individual scaffolding molecules in the postsynaptic density. Microsc Microanal. 2008 Aug;14 Suppl 2:1068-9
11. Warren Alilain, v Kevin P. Horn, Rishi Dhingra, Thomas E. Dick, Stefan Herlitze, Jerry Silver. Light induced return of motor function after spinal cord injury through a new type of respiratory plasticity. Journal of Neuroscience, 2008 Nov 12;28(46):11862-70
12. Xiaobing Chen, Nelson CD, Xiang Li, James Galbraith, Richard D. Leapman, Gainer H, Sheng M, Thomas S. Reese. PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density Journal of Neuroscience, 2011 Apr 27; 31 (17): 6329-6338
13. Xinzhu Yu, Gordon Wang, Ada Xin Yee, Xiang Li, Tonghui Xu, Stefan Smith, Lu Chen, Yi Zuo Accelerated experience-dependent pruning of cortical synapses in ephrin-A2 knockout mice. Neuron 2013 Oct 2;80(1):64-71
14. Xiang Li, Joseph Rayman, Eric Kandel, Irina Derkatch Functional Role for Tia1/Pub1 and Sup35 Prion Domains: Directing Protein Synthesis Machinery to Tubulin Cytoskeleton. Molecular Cell 2014 June 24
15. Luana Fioriti, Cory Myers, Yan-You Huang, Xiang Li, Joseph S Stephan, Pierre Trifilieff, Luca Colnaghi, Stylianos Kosmidis, Bettina Drisaldi, Elias Pavlopoulos, Eric R Kandel Persistence of long term memory storage and its reconsolidation require CPEB3-dependent protein synthesis in the hippocampus. Neuron 2015 June 17 1433-1448
16. Jennifer L. Hodges, Xinzhu Yu, Anthony Gilmore, Hannah Bennett, Michelle Tjia, James F. Perna, Chia-Chien Chen, Xiang Li, Ju Lu, Yi Zuo Astrocytic Contributions to Synaptic and Learning Abnormalities in a Mouse Model of Fragile X Syndrome Biological Psychiatry 2016