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李莉助理教授

邮  箱:lli@xmu.edu.cn

职称/职务:特任副研究员

联系方式:

  • 个人简介
  • 科研领域
  • 代表性成果

2008年,伟德国际官网登录入口生物科学专业,学士学位;
2013年,伟德国际官网登录入口细胞与分子生物学专业,博士学位;
2015-2018年,伟德BETVlCTOR1946,工程师;
2019年,伟德BETVlCTOR1946,助理教授。
B.S. 2008, Xiamen University, Life Science;
Ph.D. 2013, Xiamen University, Cellular and Molecular Biology;
Engineer, Xiamen University, 2015-2018;
Assistant Professor, School of Life Sciences, Xiamen University, 2019 to Present.

李莉博士的研究方向主要分为以下两个方面:
(1)活性天然产物药物的发现和机制研究
天然产物具有结构多样性和复杂性,是新靶点、新机制以及创新药物的绝佳来源。我们通过微生物天然产物分离以及合成生物学改造,从中发现具有生物活性的、结构新颖的天然产物,并应用化学蛋白质组学手段,解析其作用靶点和分子机制。
(2)新颖药物靶标的功能及分子调控机制研究
从重大疾病的研究入手,发现潜在的药物靶标,通过构建细胞或生化的筛选平台,获得特异性靶向潜在靶标的活性小分子,从而验证靶标可行性,同时为疾病治疗提供创新药物先导物。
Our research lies in two major areas:
(1) Discovery and mechanistic research of bioactive natural products
Natural products have long been considered as valuable source for drug development. Using traditional isolation and biosynthetic approaches, we aim to discover natural products with novel structural basis and biological activities; We further identify their direct targets and dissect the detailed molecular mechanisms by chemoproteomic approaches.
(2) Functional and regulatory mechanism study on potential therapeutic targets
We screen bioactive small molecules targeting potential therapeutic targets (such as untargeted kinases, epigenetic enzymes and so on), offer preclinical proof of concepts for therapeutic targeting these targets and provide lead compounds with novel structures.

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

1. Li, L.#; Liu, Y.#; Chen, H. Z.#; Li, F. W.#; Wu, J. F.; Zhang, H. K.; He, J. P.; Xing, Y. Z.; Chen, Y.; Wang, W. J.; Tian, X. Y.; Li, A. Z.; Zhang, Q.; Huang, P. Q.; Han, J.; Lin, T.*; Wu, Q.*, Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation. Nat Chem Biol 2015, 11 (5), 339-46.
2. Wang, Y.#; Zhang, L.#; Wei, Y.#; Huang, W.#; Li, L.#; Wu, A. A.; Dastur, A.; Greninger, P.; Bray, W. M.; Zhang, C. S.; Li, M.; Lian, W.; Hu, Z.; Wang, X.; Liu, G.; Yao, L.; Guh, J. H.; Chen, L.; Wang, H. R.; Zhou, D.; Lin, S. C.; Xu, Q.; Shen, Y.; Zhang, J.; Jurica, M. S.; Benes, C. H.; Deng, X.*, Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol 2020, 27 (11), 1359-1370 e8.
3. Li, Y.#; Liu, Z.#; Li, L.#; Lian, W.; He, Y.; Khalil, E.; Makila, E.; Zhang, W.; Torrieri, G.; Liu, X.; Su, J.; Xiu, Y.; Fontana, F.; Salonen, J.; Hirvonen, J.; Liu, W.; Zhang, H.*; Santos, H. A.*;Deng, X.*, Tandem-Mass-Tag Based Proteomic Analysis Facilitates Analyzing Critical Factors of Porous Silicon Nanoparticles in Determining Their Biological Responses under Diseased Condition. Adv Sci (Weinh) 2020, 7 (15), 2001129.
4. Chen, H. Z.#; Liu, Q. F.#; Li, L.#; Wang, W. J.; Yao, L. M.; Yang, M.; Liu, B.; Chen, W.; Zhan, Y. Y.; Zhang, M. Q.; Cai, J. C.; Zheng, Z. H.; Lin, S. C.; Li, B. A.*;Wu, Q.*, The orphan receptor TR3 suppresses intestinal tumorigenesis in mice by downregulating Wnt signalling. Gut 2012, 61 (5), 714-24.
5. Lu, Y.#; Fan, Z.#; Zhu, S. J.#; Huang, X.; Zhuang, Z.; Li, Y.; Deng, Z.; Gao, L.; Hong, X.; Zhang, T.; Li, L.; Sun, X.; Huang, W.; Zhang, J.; Liu, Y.; Zhang, B.; Jiang, J.; Gui, F.; Wang, Z.; Li, Q.; Song, S.; Huang, X.; Wu, Q.; Chen, L.; Zhou, D.; Zhang, J.; Yun, C. H.*; Chen, L.*;Deng, X.*, A new ALK inhibitor overcomes resistance to first- and second-generation inhibitors in NSCLC. EMBO Mol Med 2022, 14 (1), e14296.
6. Feng, L.#; Chen, K.#; Huang, W.#; Jiang, Y.; Sun, X.; Zhou, Y.; Li, L.; Li, Y.; Deng, X.*;Xu, B.*, Pharmacological targeting PIKfyve and tubulin as an effective treatment strategy for double-hit lymphoma. Cell Death Discov 2022, 8 (1), 39.
7. Zhang, L.#; Wang, Y.#; Huang, W.#; Wei, Y.; Jiang, Z.; Kong, L.; Wu, A. A.; Hu, Z.; Huang, H.; Xu, Q.; Li, L.;Deng, X.*, Biosynthesis and Chemical Diversification of Verucopeptin Leads to Structural and Functional Versatility. Org Lett 2020, 22 (11), 4366-4371.
8. Yang, P. B.#; Hou, P. P.#; Liu, F. Y.#; Hong, W. B.#; Chen, H. Z.#; Sun, X. Y.; Li, P.; Zhang, Y.; Ju, C. Y.; Luo, L. J.; Wu, S. F.; Zhou, J. X.; Wang, Z. J.; He, J. P.; Li, L.; Zhao, T. J.; Deng, X.; Lin, T.*;Wu, Q.*, Blocking PPARgamma interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression. Proc Natl Acad Sci U S A 2020, 117 (44), 27412-27422.
9. Li, X.#; Su, J.#; Yang, Y.#; Lian, W.; Deng, Z.; Yang, Z.; Chen, G.; Zhang, B.; Dong, C.; Liu, X.; Li, L.; Wang, Z.; Hu, Z.; Xu, Q.; Deng, X.*, Discovery of 4-methyl-N- (4-((4-methylpiperazin-1-yl)methyl) -3- (trifluoromethyl)phenyl) -3- ((6-(pyridin-3-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl)-oxy)benzamide as a potent inhibitor of RET and its gatekeeper mutant. Eur J Med Chem 2020, 207, 112755.
10. Li, W.; Ni, H.; Wu, S.; Han, S.; Chen, C.; Li, L.; Li, Y.; Gui, F.; Han, J.*;Deng, X.*, Targeting RIPK3 oligomerization blocks necroptosis without inducing apoptosis. FEBS Lett 2020, 594 (14), 2294-2302.
11. Deng, Z.#; Chen, G.#; Liu, S.; Li, Y.; Zhong, J.; Zhang, B.; Li, L.; Huang, H.; Wang, Z.; Xu, Q.; Deng, X.*, Discovery of methyl 3-((2-((1-(dimethylglycyl)-5-methoxyindolin-6-yl)amino)-5-(trifluoro-methyl) pyrimidin-4-yl)amino)thiophene-2-carboxylate as a potent and selective polo-like kinase 1 (PLK1) inhibitor for combating hepatocellular carcinoma. Eur J Med Chem 2020, 206, 112697.
12. Chen, Y.#; He, H.#; Jiang, H.#; Li, L.; Hu, Z.; Huang, H.; Xu, Q.; Zhou, R*.;Deng, X.*, Discovery and optimization of 4-oxo-2-thioxo-thiazolidinones as NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inhibitors. Bioorg Med Chem Lett 2020, 30 (7), 127021.
13. Yin, C.#; Zhu, B.#; Zhang, T.#; Liu, T.; Chen, S.; Liu, Y.; Li, X.; Miao, X.; Li, S.; Mi, X.; Zhang, J.; Li, L.; Wei, G.; Xu, Z. X.; Gao, X.; Huang, C.; Wei, Z.; Goding, C. R.; Wang, P.*; Deng, X.*;Cui, R.*, Pharmacological Targeting of STK19 Inhibits Oncogenic NRAS-Driven Melanomagenesis. Cell 2019, 176 (5), 1113-1127 e16.
14. Tian, M.#; Zeng, T.#; Liu, M.; Han, S.; Lin, H.; Lin, Q.; Li, L.; Jiang, T.; Li, G.; Lin, H.; Zhang, T.; Kang, Q.; Deng, X.*; Wang, H. R.*, A cell-based high-throughput screening method based on a ubiquitin-reference technique for identifying modulators of E3 ligases. J Biol Chem 2019, 294 (8), 2880-2891.
15. Liu, Z. H.#; Li, Y. Z.#; Li, W.; Lian, W. H.; Kemell, M.; Hietala, S.; Figueiredo, P.; Li, L.; Makila, E.; Ma, M.; Salonen, J.; Hirvonen, J. T.; Liu, D. F.; Zhang, H. B.*; Deng, X. M.*;Santos, H. A.*, Close-loop dynamic nanohybrids on collagen-ark with in situ gelling transformation capability for biomimetic stage-specific diabetic wound healing. Materials Horizons 2019, 6 (2), 385-393.
16. Gui, F.#; Jiang, J.#; He, Z.#; Li, L.; Li, Y.; Deng, Z.; Lu, Y.; Wu, X.; Chen, G.; Su, J.; Song, S.; Zhang, Y. M.; Yun, C. H.; Huang, X.; Weisberg, E.; Zhang, J.*; Deng, X.*, A non-covalent inhibitor XMU-MP-3 overrides ibrutinib-resistant Btk(C481S) mutation in B-cell malignancies. Br J Pharmacol 2019, 176 (23), 4491-4509.
17. Huang, W.#; Sun, X.#; Li, Y.; He, Z.; Li, L.; Deng, Z.; Huang, X.; Han, S.; Zhang, T.; Zhong, J.; Wang, Z.; Xu, Q.; Zhang, J.*;Deng, X.*, Discovery and Identification of Small Molecules as Methuosis Inducers with in Vivo Antitumor Activities. J Med Chem 2018, 61 (12), 5424-5434.
18. Jin, K.; Li, L.; Sun, X.; Xu, Q.; Song, S.; Shen, Y.; Deng, X.*, Mycoepoxydiene suppresses HeLa cell growth by inhibiting glycolysis and the pentose phosphate pathway. Appl Microbiol Biotechnol 2017, 101 (10), 4201-4213.
19. Jiang, J.#; Gui, F.#; He, Z.#; Li, L.; Li, Y.; Li, S.; Wu, X.; Deng, Z.; Sun, X.; Huang, X.; Huang, W.; Han, S.; Zhang, T.; Wang, Z.; Jiao, B.; Song, S.; Wang, H.; Chen, L.; Zhou, D.; Liu, Q.; Ren, R.*; Zhang, J.*;Deng, X.*, Targeting BRK-Positive Breast Cancers with Small-Molecule Kinase Inhibitors. Cancer Res 2017, 77 (1), 175-186.
20. Huang, X.#; Huang, W.#; Li, L.; Sun, X.; Song, S.; Xu, Q.; Zhang, L.; Wei, B. G.; Deng, X.*, Structure Determinants of Lagunamide A for Anticancer Activity and Its Molecular Mechanism of Mitochondrial Apoptosis. Mol Pharm 2016, 13 (11), 3756-3763.
21. Chen, Y.#; Wu, R.#; Chen, H. Z.; Xiao, Q.; Wang, W. J.; He, J. P.; Li, X. X.; Yu, X. W.; Li, L.; Wang, P.; Wan, X. C.; Tian, X. H.; Li, S. J.; Yu, X.; Wu, Q.*, Enhancement of hypothalamic STAT3 acetylation by nuclear receptor Nur77 dictates leptin sensitivity. Diabetes 2015, 64 (6), 2069-81.
22. Wang, W. J.#; Wang, Y.#; Chen, H. Z.#; Xing, Y. Z.#; Li, F. W.#; Zhang, Q.; Zhou, B.; Zhang, H. K.; Zhang, J.; Bian, X. L.; Li, L.; Liu, Y.; Zhao, B. X.; Chen, Y.; Wu, R.; Li, A. Z.; Yao, L. M.; Chen, P.; Zhang, Y.; Tian, X. Y.; Beermann, F.; Wu, M.; Han, J.; Huang, P. Q.; Lin, T.*;Wu, Q.*, Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway. Nat Chem Biol 2014, 10 (2), 133-40.
23. Lee, S. O.; Li, X.; Hedrick, E.; Jin, U. H.; Tjalkens, R. B.; Backos, D. S.; Li, L.; Zhang, Y.; Wu, Q.; Safe, S.*, Diindolylmethane analogs bind NR4A1 and are NR4A1 antagonists in colon cancer cells. Mol Endocrinol 2014, 28 (10), 1729-39.
24. Chen, H. Z.; Li, L.; Wang, W. J.; Du, X. D.; Wen, Q.; He, J. P.; Zhao, B. X.; Li, G. D.; Zhou, W.; Xia, Y.; Yang, Q. Y.; Hew, C. L.; Liou, Y. C.*;Wu, Q.*, Prolyl isomerase Pin1 stabilizes and activates orphan nuclear receptor TR3 to promote mitogenesis. Oncogene 2012, 31 (23), 2876-87.
25. Chen, H. Z.; Zhao, B. X.; Zhao, W. X.; Li, L.; Zhang, B.; Wu, Q.*, Akt phosphorylates the TR3 orphan receptor and blocks its targeting to the mitochondria. Carcinogenesis 2008, 29 (11), 2078-88.

荣誉、奖励及参加学术团体的情况:

福建省自然科学一等奖,2017年