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李勇教授博导

邮  箱:yongli@xmu.edu.cn

职称/职务:教授 博士生导师

联系方式:+86-592-2181510

  • 个人简介
  • 科研领域
  • 代表性成果

1990年,南京大学动物学专业,学士学位;
1999年,美国南佛罗里达大学分子生物学专业,博士学位;
1999-2001年,美国宾西法尼亚大学,博士后;
2001-2003年,美国大通福克斯癌症中心,博士后;
2003-2007年,美国美国范安德尔研究所,研究科学家;
2007-2010年,美国匹兹堡大学,助理教授;
2009年至今,伟德BETVlCTOR1946,闽江学者特聘教授。
B.S. 1990, Nanjing University, Zoology;
Ph.D. 1999, University of South Florida, Molecular Biology;
Postdoctoral Researcher, University of Pennsylvania, 1999-2001;
Postdoctoral Associate, Fox Chase Cancer Center, 2001-2003;
Research Scientist, Van Andel Research Institute, 2003-2007;
Assistant Professor, University of Pittsburgh, 2007-2010;
Professor, School of Life Sciences, Xiamen University, 2009 to Present.

致力于药物与靶点之间相互作用的构效关系及药物调控机制的研究,将药理学、生理学、生物化学与结构生物学等研究手段进行全新有机的结合,从药物与靶标的构效关系、药物作用的生理和病理效应以及药物调控的分子机理等方面开展全面的研究,为新药的研发提供科学依据和指导。我们在世界上率先解出了多个药物/核受体靶标的三维晶体结构,并系统阐明了这些药物调控核受体与辅调节因子特异性结合的分子机理。我们还对现有药物的新靶点、新用途和再定位 进行探索研究,已经取得了突破性成果,在药物的筛选及构效关系研究方面,发现了一系列潜在的可用于药物开发利用的新型核受体配体,并结合小鼠模型阐述了这些配体调节糖脂代谢的信号通路分子机理和药理机制,对以核受体为靶标的药理学研究与药物开发具有巨大的指导价值。
We are focusing on studying protein structure and function, as well as its implications in drug development. We intend to take advantage of the drug repositioning strategy, combined with our research experience and strength in the study of structure-activity relationship (SAR) of nuclear receptors, in developing new drugs targeting metabolic diseases with improved potency and efficacy but reduced side effects. Our investigations of structure-activity relationship with drugs and their targets, as well as with their respective signaling pathways, are revealing clinically-significant mechanisms of drug signaling in diverse disease processes and also novel strategies for therapeutic purpose.

代表性论文(# co-first author, * Corresponding author):

1. Zheng W, Lu Y, Tian S, Ma F, Wei Y, Xu S, Li Y*. Structural insights into the heterodimeric complex of the nuclear receptors FXR and RXR. J Biol Chem. 2018 Aug 10;293(32):12535-12541.
2. Wei Y, Lu Y, Zhu Y, Zheng W, Guo F, Yao B, Xu S, Wang Y, Jin L*, Li Y*. Structural basis for the hepatoprotective effects of antihypertensive 1,4-dihydropyridine drugs. Biochim Biophys Acta. 2018 Jul 23;1862(10):2261-2270.
3. Lu Y, Zheng W, Lin S, Guo F, Zhu Y, Wei Y, Liu X, Jin S, Jin L*, Li Y*. Identification of an Oleanane-type Triterpene Hedragonic Acid as a Novel Farnesoid X Receptor Ligand with Liver Protective Effects and Anti-inflammatory Activity. Mol Pharmacol. 2018 Feb;93(2):63-72.
4. Zheng W, Wang R, Liu X, Tian S, Yao B, Chen A, Jin S, Li Y*. Structural insights into the nuclear import of the histone acetyltransferase males-absent-on-the-first by importin α1. Traffic. 2018;19(1): 19-28.
5. Zheng W, Lu Y, Lin S, Wang R, Qiu L, Zhu Y, Yao B, Guo F, Jin S, Jin L, Li Y*. A Novel Class of Natural FXR Modulators with a Unique Mode of Selective Co-regulator Assembly. Chembiochem. 2017 Apr 18;18(8):721-725.
6. Jin L, Wang R, Zhu Y, Zheng W, Han Y, Guo F, Ye F.B. & Li Y*. Selective targeting of nuclear receptor FXR by avermectin analogues with therapeutic effects on nonalcoholic fatty liver disease. Sci Rep. 2015 5: 17288. doi: 10.1038/srep17288.
7. Yang C, Li Q, Li Y*. Targeting nuclear receptors with marine natural products. Mar Drugs. 2014 Jan 27;12(2):601-35.
8. Jin L, Feng X, Pan Z, Inaba Y, Qiu L, Zheng W, Lin S, Wang R, Rong H, Wang Z, Li S, Xie W, and Li Y*. The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. Nature Communications. 2013 Jun 3; 4: 1937. doi: 10.1038/ncomms2924.
9. Zheng W, Feng X, Qiu L, Pan Z, Wang R, Lin S, Hou D, Jin L*, and Li Y*. Identification of the antibiotic ionomycin as an unexpected PPARγ ligand with a unique binding mode and effective glucose-lowering activity in a mouse model of diabetes. Diabetologia. 2013 Feb; 56(2):401-11. 10. Wang S, Wang Z, Lin S, Zheng W, Wang R, Jin S, Chen J, Jin L, and Li Y*. Revealing a natural marine product as a novel agonist for retinoic acid receptors with a unique binding mode and inhibitory effects on cancer cells. 2012, Biochem J. 446(1):79-87.
11. Lin S, Han Y, Shi Y, Rong H, Zheng S, Jin S, Lin SY, Lin SC*, Li Y*. Revealing a steroid receptor ligand as a unique PPARγ agonist. 2012, Cell Res. 22(4):746-56, 2012.
12. Jin L, Lin S, Rong H, Zheng S, Jin S, Wang R, Li Y*. Structural basis for iloprost as a dual peroxisome proliferator-activated receptor alpha/delta agonist. J Biol Chem. 2011, 286(36):31473-9.
13. Jin L, Li Y*. Structural and functional insights into nuclear receptor signaling. Adv Drug Deliv Rev. 2010, 62: 1218–1226.
14. Jin L, Martynowski D, Zheng S, Wada T, Xie W, and Li Y*. Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORγ. Molecular Endocrinology, 2010, 24(5): 923-929.
15. Xu HE* and Li Y*. Ligand-dependent and -independent regulation of PPAR gamma and orphan nuclear receptors. Sci. Signal 2008, 1(48), pe52.
16. Li Y*, Zhang J, Schopfer F, Martynowski D, Garcia-Barrio M, Kovach A, Suino-Powell K, Baker P, Freeman B, Chen Y, and Xu HE*. Molecular recognition of nitro-fatty acids by PPARγ. Nature Structural & Molecular Biology 2008. 15(8):865-7.
17. Li Y*, Kovach A, Suino-Powell K, Martynowski D, and Xu HE*. Structural and Biochemical Basis for the Binding Selectivity of PPARγ to PGC1α. J Biol Chem. 2008. 283(27):19132-9. (IF: 5.581)
18. Motola D, Cummins L, Rottiers V, Sharma K, Li T, Li Y, Powell K, Xu HE, Auchus RJ, Antebi A, and Mangelsdorf DJ. Identification of Ligands for DAF-12 that Govern Dauer Formation and Reproduction in C. elegans. Cell 2006.124(6):1209-1223.

荣誉、奖励及参加学术团体的情况: