Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

LI Ping was graduated with his PhD degree from Shanghai Institute of Material Medica (SIMM) and received his postdoctoral in Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences and University of Michigan sequentially. He has joined into SIMM since January, 2021. And his interests are focusing on the drug development for neurodegenerative disorders and metabolic diseases. Generally, he is hunting for novel ion channels residing on the intracellular membrane of cells, like lysosomes, autophagosomes, endoplasmic reticulum, mitochondria etc, and their physiological/pathological roles in neurodegenerative disorders and metabolic diseases.

Education

2009.09-2014.07 SIMM, Neuropharmacology, SIMM, CAS

2005.09 - 2009.06 Hubei University, Chemical Biology, Bachelor

Work Experience

2015.10-2020.10 Professor, Department of Neuropharmacology, SIMM, CAS;

2014.07-2015.06 Postdoctoral in SIAT, CAS

Research Directions

1. drug development targeting on organellar ion channels for neurodegenerative disorders and metabolic diseases

Grants & Research Projects

Achievements

1.During doctoral phase, my study identified the voltage sensor domain of Kv7.2 as a novel target for anti-epilepsy drugs (Li et al., Cell Research, 2013). By screening 220,000 small chemicals, 9 agonists of Kv7.2 with different molecular skeleton were first obtained through the combination of the high throughput screening, whole-cell patch clamp recording, and the computer-aid virtual screening. 4 of agonists demonstrated excellent anti-epilepsy effects with more than 90% inhibition in the epilepsy mouse model. More importantly, 2 agonists exhibited the comparable anti-epilepsy effects with the FDA approved anti-convulsive drug (Retigabine). After my publication, Dr. Bernard Attali from Tel Aviv University of Israel specifically wrote a commentary paper in Cell Research that respects our work in leading the novel anti-epilepsy drug development and hunting drugs for patients with refractory epilepsy.

2.Restricted with the shortage of investigation methods, researches of organellar physiologies in cells are pushed forward slowly. As the whole-endolysosome patch clamp recording originally established by Dr. Haoxing Xu at University of Michigan develops, explorations the physiologies and pathologies of ion channels expressed on lysosome and autophagosome membranes are recently coming hot-spots. My first project finished in Dr. Haoxing Xu`s lab discovered a new role of lysosomes, acting as the “cellular bladder” (Li et al., PNAS, 2020). I provide compelling evidence that in individual cells, lysosomes sequester, then extrude toxic levels of intracellular water, to help alleviate the water crisis, comparable with the “charging” and “discharging” phases of the bladder organ. Furthermore, I determined that an ionic-strength-sensitive Lyso-VRAC in lysosomal membranes orchestrates the lysosome osmoregulatory behavior. In current physiology textbooks, cell volume is described as only executed by the plasma membrane, which helps passively extrude H2O from the cytosol. My work now reports that a second mechanism, “active” H2O extrusion mediated by lysosomes, also plays an essential role in cell volume. Thus, this work is a breakthrough study switching the cell volume regulation from the cell surface to the intracellular organelle, and could be helpful for disclosure of human metabolic disorders from the organellar angle.

3.As the longevity of human life gradually achieves, Parkinson`s disorder (PD) is becoming one of the priory diseases decreasing the life quality of senior population significantly. This urges to validate new drug targets for PD treatments. My second project completed during the postdoc period originally discovered a novel protein as the lysosome proton channel is potential to be first intracellular target for PD drug discovery (Hu&Li et al., in submission). My results showed the agonist cleaned the accumulation of PD biomarker in the brain of PD mouse dramatically. Therefore, this work will light up the novel PD drug discovery targeting at the lysosome proton channel, and lead frontier studies that interpret relationships of human neurodegenerative diseases with lysosome ion channels.

4.The screening and discovery of leading hits targeting at the ion channels are very important for the drug development, as ion channels are the second druggable membrane proteins for the launched drugs. I have participated plenty of screenings of ion channel drugs, and acquired a series of leading hits with various molecular skeletons. I patented urea and thiourea compounds activating Kv7.2 channels as the potent anti-epilepsy drugs in the mouse model. I found natural products, Chukrasones, are the Kv1.2 channel inhibitor that could be useful for atxia patient treatment. I disclosed another nature product, vindoline, increases insulin releasing and consequentially regulates glucose metabolism as the Katp channel inhibitor. I discovered modulators of TRPML1 channel are able to treat “heart-burn” patients with disturbed gastric acid secretion, Duchenne muscular dystrophy disease, and neurodegenerative diseases.

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Social Titles

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Awards & Honors

1.Gordon Research Conferences, Seminar Meeting Travel Award, 2019;

2.“ZhuLi YueHua” Outstanding Graduates of Chinese Academy of Sciences, 2014;

3.National Scholarship for Ph.D candidates, 2013;

4.First award for outstanding research articles in Pudong New Distract of Shanghai, 2013;

5.“All-around good student” of Chinese Academy of Sciences, 2013

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Pubilcations

Full Publication List

Selected Publications

1.Ping Li#,*, Meiqin Hu, Ce Wang, Xinghua Feng, Zhuangzhuang Zhao, Ying Yang, Nirakar Sahoo, Mingxue Gu, Yexin Yang, Shiyu Xiao, Rajan Sah, Timothy L. Cover, Janet Chou, Raif Geha, Fernando Benavides, Richard I. Hume* and Haoxing Xu, LRRC8 family proteins within Lysosomes Regulate Cellular Osmoregulation and Enhance Cell Survival to Multiple Physiological Stresses. PNAS;2020 Nov. 17;117(46):29155-29165;

2.Ping Li#, Zhuxi Chen#, Haiyan Xu, Haifeng Sun, Hao Li, Hong Liu, Huaiyu Yang, Zhaobing Gao*, Hualiang Jiang*, and Min Li, The gating charge pathway of an epilepsy-associated potassium channel accommodates chemical ligands. Cell Research 2013 Sep; 23(9); 1106-18;

3. Li P#, Gu M# and Xu H*. Lysosomal ion channels as decoders of cellular signals. Trends in Biochemical Sciences; 2019 Feb; 44(2):110-124.

4.Xiaoli Zhang#, Wei Chen#, Ping Li#, Raul Calvo, Noel Southall, Xin Hu, Melanie Bryant-Genevier, Xinghua Feng, Qi Geng, Chenlang Gao, Meimei Yang, Kaiyuan Tang, Marc Ferrer, Jan Jose Marugan, Haoxing Xu*, Agonist-specific voltage-dependent gating of lysosomal two-pore Na+ channels. eLife 2019;8:e51423.

5. Li P#, Chen X, Zhang Q, Zheng Y, Jiang H, Yang H, Gao Z*. The human ether-a-go-go-related gene activator NS1643 enhances epilepsy-associated KCNQ channels. J Pharmacol Exp Ther. 2014 Dec; 351(3): 596-604.

6. Ping Li#, Jin Zhu, Qingya Kong, Baifeng Jiang, Xia Wan, Jinfeng Yue, Min Li, Hualiang Jiang, Jian Li, Zhaobing Gao*. The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2 potassium channel. Toxicology Letters, 2013 June 7; 219(3): 211-7;

7.Ping Li#, Hai-feng SUN, Ping-Zheng ZHOU, Chao-ying MA, Guo-yuan HU, Hua-liang JIANG, Min LI, Hong LIU, Zhao-bing GAO*. The inhibitory effects of DC031050，a class III antiarrhythmic agent with high selectivity for hERG channels, on three neuronal potassium channels. Acta Pharmacologica Sinica, 2012 June; 33(6): 728-736;

8.Meiqin Hu#,*, Ping Li#, Ce Wang, Xinghua Feng, Qi Geng, Wei Chen, Matangi Marthi, Chenlang Gao, Whitney Reid, Joel Swanson, Wanlu Du, Richard I. Hume, and Haoxing Xu, Parkinson`s Disease-linked LyPAP Is a Proton-selective Ion Channel in The Endosome and Lysosome. (in submission)

9.Huaiyu Yang#, Zhaobing Gao#, Ping Li, Kunqian Yu, Ye Yu, Tianle Xu, Min Li, and Hualiang Jiang*. A theoretical Model for Calculating Voltage Sensitivity of Ion Channels and the Application on Kv1.2 Potassium Channel. Biophysical Journal, 2012 April 18; 102(8): 1815-25;

10. Hong-Bing Liu#, Hua Zhang, Ping Li, Yan Wu, Zhao-Bing Gao and Jian-Min Yue*. Kv1.2 potassium cahnnel inhibitors from Chukrasia tabularis. Organic Biomolecular Chemistry, 2012, Feb 21; 10(7): 1448-1458;

11.Hong-Bing Liu#, Hua Zhang, Ping Li, Zhao-Bing Gao,and Jian-Min Yue*. Chukrasones A and B: Potential Kv1.2 Potassium Channel Blockers with New Skeletons from Chukrasia tabularis. Organic Letters, 2012 sep 7; 14(17): 4438-41;

12. Yao XG#, Chen F, Li P, Quan L, Chen J, Yu L, Ding H, Li C, Chen L, Gao Z, Wan P, Hu L, Jiang H*, Shen X*. Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models. J Ethnopharmacol. 2013 Oct 28; 150(1): 285-97;

13.Wan X#, Lu Y, Chen X, Xiong J, Zhou Y, Li P, Xia B, Li M, Zhu MX, Gao Z*. Biomodal voltage dependence of TRPA1: mutations of a key pore helix residue reveal strong intrinsic voltagedependent inactivation. Pflugers Arch. 2014 Jul; 466(7): 1237-87;

14. Fang Bai#, Xiaoping Pi#, Ping Li, Pingzheng Zhou, Huaiyu Yang, Xicheng Wang, Min Li, Zhaobing Gao* and Hualiang Jiang*. A statistical thermodynamic model for ligands interacting with ion channels: theoretical model and experimental validation of the KCNQ2 channel. Frontier in Pharmacology; 2018 March 9; 9:150;

15. Wang W#, Zhang X, Gao Q, Lawas M, Yu L, Cheng X, Gu M, Sahoo N, Li X, Li P, Ireland S, Meredith A and Xu H*. A voltage-dependent K channel in the lysosome is required for refilling lysosomal Ca2+ stores. Journal of Cell Biology; 2017 Jun 5; 216(6):1715-1730.

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