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Biography

Yuanyuan Li, Ph.D., Principal Investigator of Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Principal Investigator of Zhongshan Institute for Drug Discovery, the Institutes of Drug Discovery and Developments, Chinese Academy of Sciences. She was graduated with her PhD degree from SIMM and received her postdoctoral training at Johns Hopkins University, Northeast Ohio Medical University and Baylor College of Medicine. Her research is centered on elucidation of pathogenesis and identification of novel therapeutic targets of metabolic disorders, such as non-alcoholic fatty liver diseases, diabetes and atherosclerosis. She has published 25 papers, including 9 papers published as first or co-first author in high profile journals, such as Nature Metabolism, Hepatology, Arteriosclerosis, Thrombosis, and Vascular Biology, etc. The total citations of her papers are beyond 1000, with a H index of 18. She also has rich experiences in Drug development. As one of the primary participants in the drug development program, she has developed more than 10 novel small molecules with the potential for Diabetes treatment.  

Education:

2004.09 - 2010.01  Ph.D. Shanghai Institute of Materia Medica

2000.09 - 2004.06  B.S. Huazhong University of Science and Technology

Work Experience:

2020.08-Present   Principal investigator, Shanghai Institute of Materia Medica, Chinese Academy of Sciences; Principal investigator, Zhongshan Institute for Drug Discovery, the Institutes of Drug Discovery and Developments, Chinese Academy of Sciences

2019.10-2020.06   Postdoctoral Fellow, Baylor College of Medicine

2012.09-2018.04   Postdoctoral Fellow, Northeast Ohio Medical University

2010.09-2012.08   Postdoctoral Fellow, Johns Hopkins University

Research Directions

Mechanism Study and Drug Development for Metabolic Disorders, such as non-alcoholic fatty liver diseases, Diabetes and Atherosclerosis

Achievements

1.Identification of CES1 and CES2 participating in the pathogenesis of NAFLD as novel TG hydrolases for the first time, and validation of them as promising targets for NAFLD treatment. Elucidation of the mechanism of OCA in NAFLD treatment, a drug which has achieved its endpoint in its Phase III clinical trial. These results are published in Hepatology,2014:59:1761-177 and Hepatology, 2016:63:1860-1874, and highly recommended by experts of Faculty of 1000.

2.Identification of several novel promising pathways for atherosclerosis treatment, such as FOXA3-ApoAI, ATF3-Cyp8b1/SR-B1 pathway, etc. Demonstration of AAV-FOXA3 as a promising gene therapy for atherosclerosis. These results are published in Nature Metabolism, 2021, 3(1):59-74 and Arteriosclerosis, Thrombosis, and Vascular Biology, 2019, 39(8):1574-1587.

3.Participation in the development of several novel small molecules for the treatment of Type 2 Diabetes, such as AMPK activators, DPPIV inhibitors, etc. These work are published in Toxicol Appl Pharm, 2013:273(2):325-34， ACS Med. Chem. Lett., 2013:4 (5): 475–480，ChemMedChem, 2013:8(7):1104-16，Acta Pharmacologica Sinica, 2010:31:1005–1012. Patent PCT/CN2006/001596 was applied.  

Publications

1. Yanyong Xu#, Yuanyuan Li#, Kavita Jadhav#, Xiaoli Pan, Yingdong Zhu, Shuwei Hu, Shaoru Chen, Liuying Chen, Yong Tang, Helen H Wang, Ling Yang, David Q-H Wang, Liya Yin, Yanqiao Zhang. Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism. Nature Metabolism, 2021, 3(1):59-74(# Co-first author)

2. Yuanyuan Li#, Yanyong Xu#, Kavita Jadhav, Liya Yin and Yanqiao Zhang. Hepatic forkhead box protein A3 regulates ApoA I expression, cholesterol efflux and atherogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 2019, 39(8):1574-1587(# Co-first author)

3. Yuanyuan Li, Munaf Zalzala, Kavita Jadhav, Yang Xu, Takhar Kasumov, Liya Yin and Yanqiao Zhang. Carboxylesterase 2 Prevents Liver Steatosis by Modulating Lipolysis, ER stress and Lipogenesis and is regulated by Hepatocyte Nuclear Factor 4 Alpha in Mice. Hepatology, 2016, 63:1860-1874

4. Jiesi Xu #, Yuanyuan Li #, Wei Dong Chen #, Yang Xu #, Liya Yin, Xuemei Ge, Kavita Jadhav, Luciano Adorini, and Yanqiao Zhang. Hepatic Carboxylesterase 1 Is Essential for Both Normal and Farnesoid X Receptor Controlled Lipid Homeostasis. Hepatology, 2014, 59:1761-1771 (# Co-first author) Received Editorial Comment in Hepatology, 2014 59:1665-7 and Highlighted by Faculty of 1000

5.Yuanyuan Li, Kavita Jadhav, and Yanqiao Zhang. Bile acid receptors in non-alcoholic fatty liver disease. Biochem Pharmacol, 2013, 86(11):1517-24

6.Yuan-Yuan Li#, Li-Fang Yu#, Li-Na Zhang, Bei-Ying Qiu, Ming-Bo Su, Fang Wu, Tao Pang, Min Gu, Wei Zhang, Da-Kai Chen,Wei-Ping Ma, Jing-Ya Li*, Fa-Jun Nan*, Jia Li*. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice. Toxicol Appl Pharm, 2013, 273(2):325-34(# Co-first author)

7. Li-Fang Yu#, Yuan-Yuan Li#, Ming-Bo Su, Mei Zhang , Wei Zhang , Li-Na Zhang , Tao Pang , Run-Tao Zhang , Bing Liu , Jing-Ya Li*, Jia Li*, and Fa-Jun Nan*. Development of Novel Alkene Oxindole Derivatives As Orally Efficacious AMP-Activated Protein Kinase Activators. ACS Med. Chem. Lett., 2013, 4 (5): 475–480 (# Co-first author)

8. Linrong Zhu#, Yuanyuan Li#, Qiu Ling, Mingbo Su, Xin Wang, Chunmei Xia, Yi Qu, Jingya Li, Jia Li*, Bin Xiong*, Jingkang Shen*. Design and Synthesis of 4-(2,4,5-Trifluorophenyl)butane-1,3-diamines as Dipeptidyl Peptidase IV Inhibitors. ChemMedChem, 2013, 8(7):1104-16 (# Co-first author)

9. Zhang Liu#, Qian Chai #, Yuanyuan Li #, Qiang Shen, Lanping Ma*, Lina Zhang, Xin Wang, Li Sheng, Jingya Li, Jia Li*, Jingkang Shen. Discovery of novel PTP1B inhibitors with antihyperglycemic activity. Acta Pharmacologica Sinica, 2010, 31:1005–1012 (# Co-first author)

10. Yanyong Xu, Xiaoli Pan, Shuwei Hu, Yingdong Zhu, Fathima Cassim Bawa, Yuanyuan Li, Liya Yin, Yanqiao Zhang. Hepatocyte-specific Expression of Human Carboxylesterase 2 Attenuates Non-alcoholic Steatohepatitis in Mice. Am J Physiol Gastrointest Liver Physiol. 2020 Dec 16. Online ahead of print.

11. Yanyong Xu, Yingdong Zhu, Kavita Jadhav, Yuanyuan Li, Huihui Sun, Liya Yin, Takhar Kasumov, Xiaoli Chen, Yanqiao Zhang. Lipocalin-2 Protects Against Diet-Induced duced Nonalcoholic Fatty Liver Disease by Targeting Hepatocytes. Hepatology Communications, 2019, 3:763-775

12. Kavita Jadhav#, Yang Xu#, Yanyong Xu#, Yuanyuan Li, Jiesi Xu, Yingdong Zhu, Luciano Adorini, Yoon Kwang Lee, Takhar Kasumov, Liya Yin, Yanqiao Zhang. Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR. Molecular Metabolism, 2018, 9:131-140

13. Jiesi Xu, Yang Xu, Yuanyuan Li, Kavita Jadhav, Min You, Liya Yin & Yanqiao Zhang (2016). Carboxylesterase 1 Is Regulated by Hepatocyte Nuclear Factor 4α and Protects Against Alcohol- and MCD diet-induced Liver Injury. Scientific Reports, 2016, 6:24277

14. Michael L. Multhaup, Marcus M. Seldin, Andrew E. Jaffe, Xia Lei, Henriette Kirchner, Prosenjit Mondal, Yuanyuan Li, Varenka Rodriguez, Alexander Drong, Mehboob Hussain, Cecilia Lindgren, Mark McCarthy, Erik Naslund, Juleen R. Zierath, G. William Wong, Andrew P. Feinberg. Mouse-Human Experimental Epigenetic Analysis Unmasks Dietary Targets and Genetic Liability for Diabetic Phenotypes. Cell Metabolism, 2015, 21(1):138-49 Received Editorial Comment in Nature Reviews Endocrinology, 2015:11(5):261-2

15. Yang Xu#, Munaf Zalzala#, Jiesi Xu, Yuanyuan Li, Liya Yin, Yanqiao Zhang. A metabolic stress-inducible miR-34a-HNF4α pathway regulates lipid and lipoprotein metabolism. Nature communications, 2015, 6:7466

16. Prosenjit Mondal#, Woo-Jin Song#, Yuanyuan Li, Kil S. Yang, and Mehboob A. Hussain. Increasing β-Cell Mass Requires Additional Stimulation for Adaptation to Secretory Demand. Mol Endocrinol., 2015, 29(1):108-20

17. Ryan C. Riddle, Julie M. Leslie, Mathieu Ferron, Yuanyuan Li, Douglas J.Digirolamo, Marie-Claude Faugere, Mehboob A. Hussain, Gerard Karsenty and Thomas L. Clemens. Tsc2 Is a Molecular Checkpoint Controlling Osteoblast Development and Glucose Homeostasis. Mol Cell Biol., 2014:34(10):1850-62

18. Jiesi Xu, Liya Yin, Yang Xu, Yuanyuan Li, Munaf Zalzala, Gang Cheng, Yanqiao Zhang. Hepatic Carboxylesterase 1 Is Induced by Glucose and Regulates Postprandial Glucose Levels. PLoS ONE, 2014, 9(10):e109663

19. Woo-Jin Song#, Prosenjit Mondal#, Yuanyuan Li, Suh Eun Lee and Mehboob A. Hussain. Pancreatic β-cell Response to Increased Metabolic Demand and to Pharmacologic Secretagogues Requires EPAC2A. Diabetes, 2013, 62(8):2796-807 Received Editorial Comment in Diabetes, 2013,62(8):2665-6

20. Li-Na Zhang, Hua-Yong Zhou, Yan-Yun Fu, Yuan-Yuan Li, Fang Wu, Min Gu, Ling-Yan Wu, Chun-Mei Xia, Tian-Cheng Dong, Jing-Ya Li*, Jing-Kang Shen*, and Jia Li*. Novel Small-Molecule PGC-1α Transcriptional Regulator With Beneficial Effects on Diabetic db/db Mice. Diabetes, 2013, 62(4):1297-307

21. Li-Na Zhang, Lei Xu, Hua-Yong Zhou, Ling-Yan Wu, Yuan-Yuan Li, Tao Pang, Chun-Mei Xia, Bei-Ying Qiu, Min Gu, Tian-Cheng Dong, Jing-Ya Li*, Jing-Kang Shen*, Jia Li*. Novel Small-Molecule AMP-Activated Protein Kinase Allosteric Activator with Beneficial Effects in db/db Mice. PLoS ONE, 2013, 8(8):e72092

22. Beiying Qiu, Turner N, Yuanyuan Li, Ming Gu, Mingwei Huang, Fang Wu, Tao Pang, Fajun Nan, Jiming Ye, Jingya Li*, Jia Li*. High-Throughput Assay for Modulators of Mitochondrial Membrane Potential Identifies a Novel Compound With Beneficial Effects on db/db Mice. Diabetes, 2010, 59:256–265

23. Zhe Cheng#, Anfeng Chen#, Fang Wu, Li Sheng, Hankun Zhang, Min Gu, Yuanyuan Li, Lina Zhang, Lihong Hu*, Jingya Li*, Jia Li*. 8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models. Bioorganic & Medicinal Chemistry, 2010, 18:5915–5924

24. Guanghui Deng, Deju Ye, Yuanyuan Li, Lingyan He, Yu Zhou, Jiang Wang, Jia Li, Hualiang Jiang, Hong Liu. Synthesis of (S)-, (R)-, and (rac)-2-amino-3,3-bis(4-fluorophenyl) propanoic acids and an evaluation of the DPP IV inhibitory activity of Denagliptin diastereomers. Tetrahedron, 2008, 64(46):10512-10516

25. Xiang Guang-ya, Liang Rong-bei, Li Yan-ping, Li Yuanyuan. Synthesis of NO-releasing oxaprozin and determination of NO-releasing activities in vitro. Central South Pharmacy, 2005, 3(4):206