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李勤喜教授博导

邮  箱:liqinxi@xmu.edu.cn

职称/职务:教授 博士生导师

联系方式:0592-2183839

  • 个人简介
  • 科研领域
  • 代表性成果

1995年,兰州医学院(现兰州大学医学院)临床医学专业,学士学位;
1998年,兰州医学院(现兰州大学医学院)临床血液学,硕士学位;
2001年,兰州大学无机化学,理学博士;
2003-2005年,香港科技大学,访问学者;
2010-2011年,多伦多大学,博士后;
2001年至今,澳门大阳城集团澳门大阳城集团2138网站,助理教授/副教授/教授;
2017年至今,澳门大阳城集团澳门大阳城集团2138网站,副院长。
B.S. 1995, Lanzhou Medical College, Clinical Medicine;
M.S. 1998, Lanzhou Medical College, Clinical Hematology;
Ph.D. 2001, Lanzhou University, Inorganic Chemistry;
Visiting Scholar, Hongkong University of Science and Technology, 2003-2005;
Postdoc Fellow, University of Toronto, 2010-2011;
Assistant Professor/Associate Professor/Professor, School of Life Sciences, Xiamen University, 2001 to Present;
Vice Dean, School of Life Sciences, Xiamen University, 2017 to Present.

1. 异柠檬酸脱氢酶1(IDH1)R132H/Q突变体致癌的机理
IDH1-R132H/Q突变与多种肿瘤,特别是胶质瘤的发生密切相关。研究表明该突变体能产生大量的2-羟基戊二酸(2-HG),2-HG作为癌性代谢产物导致了肿瘤的发生,但2-HG致癌的机理仍待进一步阐明。我们从2-HG引起代谢紊乱及细胞凋亡异常方面入手对其致癌机理进行研究,鉴定2-HG引起代谢紊乱的靶点,开发针对这些靶点的抗肿瘤药物。


(Cell Rep. 2017 Apr 11; 19(2): 389-400) (Cell Rep. 2017 May 30; 19(9): 1846-1857)
2. 原癌基因c-src通过改变细胞代谢模式促进肿瘤发生和转移的分子机制
肿瘤细胞代谢的一大特征是出现Warburg effect,即在有氧的情况下,肿瘤细胞主要通过提高无氧代谢糖酵解的效率来供应能量及生物合成的原料,并伴有大量乳酸的生成。这种代谢改变对肿瘤细胞的生长、增殖及迁移起重要作用。c-src是一个非常重要的原癌基因,其蛋白产物c-Src是第一个被发现的酪氨酸激酶。c-Src的高表达或过度激活与多种肿瘤的发生和转移密切相关,但其调控细胞代谢的机理还不清楚。我们研究c-Src通过改变细胞代谢模式在肿瘤发生和转移中的作用。
(c-Src通过激活有氧糖酵解促进肿瘤发生发展)
3. 谷氨酰胺酶GLS1在营养应激、肿瘤发生及器官发育中的作用
GLS1是谷氨酸分解代谢的关键酶,目前的研究表明其在多种恶性肿瘤中高表达,促进肿瘤增殖,因此,被认为是一个重要的肿瘤治疗靶点。我们研究发现在谷氨酰胺缺乏的情况下,GLS1能通过感受其产物谷氨酸的浓度进行结构重塑,高度激活其酶活性,进而导致细胞死亡。目前,我们在进一步研究GLS1在营养应激、肿瘤发生及器官发育中的作用,筛选能通过激活GLS1抑制肿瘤生长的小分子化合物。

GLS1通过结构重塑促进谷氨酰胺缺乏引起的细胞的机理(Mol Cell, 2022 May 19)
4. 抑癌因子p53调控肿瘤代谢的新机理
抑癌因子p53的功能缺失与多种肿瘤发生有关,其被发现能抑制Warburg effect。我们主要研究p53对生物合成及脂代谢的调节作用。

1. Mechanisms underlying tumorigenesis driven by isocitrate dehydrogenase 1 (IDH1) R132H/Q mutations. IDH1-R132H/Q mutations are related to the generation and development of various tumors, in particular glioma. It has been well understood that it is the large amount of 2-hydroxyglutarate (2-HG) produced by these mutants that leads to tumorigenesis. However, the mechanism by which 2-HG results in tumorigenesis remains far to be clarified. We are working on the metabolic and apoptotic disorders caused by 2-HG, which may play important roles in 2-HG induced tumorigenesis.
2. The roles of metabolic alterations caused by proto-oncogene c-src in tumorigenesis and metastasis. One hallmark of cancer cell metabolism is Warburg effect, a metabolic alteration that even in the presence of oxygen, cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation. This metabolic switch is essential for cancer cells to maintain survival, proliferation and mobility. c-src is an important proto-oncogene that encodes c-Src protein, the firstly identified tyrosine kinase. Excessive expression and/or activation of c-Src contribute to the generation and metastasis of various tumors. However, little is known about how c-Src regulates metabolism of tumor cells. One of our goals is to clarify the contribution of metabolic alterations caused by proto-oncogene c-Src to tumorigenesis and metastasis.
3. The roles of Glutaminase 1 (GLS1) in nutrient stress, tumorigenesis and organ development
GLS1, a key enzyme in glutamine catabolism, is considered as an important target for tumor therapy because it is excessively expressed in various tumor and functions to stimulated tumor proliferation. We find that upon glutamine deprivation, the structure of GLS1 is remodelled by the lower concentration of its product glutamate to stimulate its enzymatic activity which in turn leads to cell death. We are now engaged in the studies to clarify the roles of GLS1 in nutrient stress, tumorigenesis and organ development. We are also interested in screening small molecules showing strong anti-tumor activity by stimulating GLS1 activity.
4. The novel mechanisms underlying metabolic regulation by p53. Deficiency of tumor suppressor p53 is high correlated with the incidence of various tumors. p53 has been found participating in the suppression of Warburg effect, a hallmark of cancer. We focus on the regulatory effect of p53 on biosynthesis and lipid metabolism of cancer cells.

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

1. Jiang B, Zhang J, Zhao G, Liu M, Hu J, Lin F, Wang J, Zhao W, Ma H, Zhang C, Wu C, Yao L, Liu Q, Chen X, Cao Y, Zheng Y, Zhang C, Han A, Lin D, Li Q*. Filamentous GLS1 promotes ROS-induced apoptosis upon glutamine deprivation via insufficient asparagine synthesis. Molecular Cell 2022 May 19; 82(10):1821-1835.e6. doi: 10.1016/j.molcel.2022.03.016
2. Zhou Y, Lin F, Wan T, Chen Ai, Wang H, Jiang B, Zhao W, Liao S, Wang S, Li G, Xu Z, Wang J, Zhang J, Ma H, Lin D, Li Q*. ZEB1 enhances Warburg effect to facilitate tumorigenesis and metastasis of HCC by transcriptionally activating PFKM. Theranostics 2021 April 03; 11(12):5926-5938.
3. Ma H, Zhang F, Zhou L, Cao T, Sun D, Wen S, Zhu J, Xiong Z, Tsau M-T, Cheng M-L, Hung L-M, Zhou Y, Li Q*. c-Src facilitates tumorigenesis by phosphorylating and activating G6PD. Oncogene 2021 March 08; 40:2567–2580.
4. Ma H, Zhang J, Zhou L, Wen S, Tang HY, Jiang B, Zhang F, Suleman M, Sun D, Chen A, Zhao W, Lin F, Tsau MT, Shih LM, Xie C, Li X, Lin D, Hung LM*, Cheng ML*, Li Q*. c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3. Cell Rep. 2020 Mar 24; 30(12):4235-4249.e6.
5. Suleman M, Chen A, Ma H, Wen S, Zhao W, Lin D, Wu G*, Li Q*. PIR promotes tumorigenesis of breast cancer by upregulating cell cycle activator E2F1. Cell Cycle. 2019 Nov; 18(21):2914-2927.
6. Jiang B, Zhao W, Shi M, Zhang J, Chen A, Ma H, Suleman M, Lin F, Zhou L, Wang J, Zhang Y, Liu M, Wen S, Ouyang C, Wang H, Huang X*, Zhou H*, Li Q*. IDH1 R132 mutant promotes tumor formation through downregulating p53. J. Biol. Chem. 2018 Jun 22; 293(25):9747-9758
7. Yang Z, Jiang B, Wang Y, Ni H, Zhang J, Xia J, Shi M, Hung L-M, Ruan J, Mak TW, Li Q* and Han J*. 2-HG Inhibits Necroptosis by Stimulating DNMT1-Dependent Hypermethylation of the RIP3 Promoter. Cell Reports. 2017 May 30; 19(9): 1846-1857.
8. Jiang B, Zhang J, Xia J, Zhao W, Wu Y, Shi M, Luo L, Zhou H, Chen A, Ma H, Zhao Q, Suleman M, Lin F, Zhou L, Wang J, Zhang Y, He Y, Li X, Hung LM, Mak TW, Li Q*. IDH1 Mutation Promotes Tumorigenesis by Inhibiting JNK Activation and Apoptosis Induced by Serum Starvation. Cell Reports. 2017 Apr 11; 19(2): 389-400.
9. Zhang J, Wang S, Jiang B, Huang L, Ji Z, Li X, Zhou H, Han A, Chen A, Wu Y, Ma H, Zhao W, Zhao Q, Xie C, Sun X, Zhou Y, Huang H, Suleman M, Lin F, Zhou L, Tian F, Jin M, Cai Y, Zhang N, Li Q*. c-Src phosphorylation and activation of hexokinase promotes tumorigenesis and metastasis. Nature Communications. 2017 Jan 5; 8:13732.
10. Inoue S, Li WY, Tseng A, Beerman I, Elia AJ, Bendall SC, Lemonnier F, Kron KJ, Cescon DW, Hao Z, Lind EF, Takayama N, Planello AC, Shen SY, Shih AH, Larsen DM, Li Q, Snow BE, Wakeham A, Haight J, Gorrini C, Bassi C, Thu KL, Murakami K, Elford AR, Ueda T, Straley K, Yen KE, Melino G, Cimmino L, Aifantis I, Levine RL, De Carvalho DD, Lupien M, Rossi DJ, Nolan GP, Cairns RA, Mak TW. Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2. Cancer Cell. 30(2): 337-48. 2016, Aug 8.
11. Liu Q, Cheng Z, Luo L, Yang Y, Zhang Z, Ma H, Chen T, Huang X, Lin S-Y, Jin M, Li Q*, Li X*. C-terminus of MUC16 activates Wnt signaling pathway through its interaction with β-catenin to promote tumorigenesis and metastasis. Oncotarget. 14; 7(24): 36800-36813. 2016, May 5.
12. Xu M, Cai C1, Sun X, Chen W, Li Q*, Zhou H*. Clnk plays a role in TNF-alpha-induced cell death in murine fibrosarcoma cell line. Biochem Biophys Res Commun. 463(3): 275-9. 2015, Jul 31.
13. Ying He, Guili Lian, Shuyong Lin, Zhiyun Ye, Qinxi Li*. MDM2 Inhibits Axin-induced p53 Activation Independently of Its E3 Ligase Activity. PLOS ONE, 8(6): e67529. 2013, Jun 27.
14. Guo HL, Zhang C, Liu Q, Li Q, Lian G, Wu D, Li X, Zhang W, Shen Y, Ye Z, Lin SY, Lin SC. The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation. Cell Res. 22(8): 1246-1257. 2012, Apr.
15. Lin SY, Li TY, Liu Q, Zhang C, Li X, Chen Y, Zhang SM, Lian G, Liu Q, Ruan K, Wang Z, Zhang CS, Chien KY, Wu J, Li Q, Han J, Lin SC. GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy. Science. 336(6080): 477-81, 2012, Apr 27.
16. Li Q, He Y, Wei L, Wu X, Wu D, Lin S, Wang Z, Ye Z, Lin SC., AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation. Oncogene. 30(10): 1194-1204, 2011.
17. Li Q., Lin S., Wang X., Lian G., Lu Z., Guo H., Ruan K., Wang Y., Ye Z., Han J. and Lin S.-C., Axin determines cell fates by controlling p53 activation threshold upon DNA damage. Nature Cell Biology. 11(9): 1128-1134, 2009.
18. Li Q.,*, Ye Z., Wen J., Ma L., He Y., Lian G., Wang Z., Wei L., Wu D. and Jiang B., Gelsolin, but not its cleavage, is required for TNF-induced ROS generation and apoptosis in MCF-7 cells. Biochem. Biophys. Res. Commun. 385(2): 284-289, 2009.
19. Zhan, Y., Du, X., Chen, H., Liu, J., Zhao, B., Huang, D., Li, G., Xu, Q., Zhang, M., Weimer, B.C., Chen, D., Cheng, Z., Zhang, L., Li, Q., Li, S., Zheng, Z., Song, S., Huang, Y., Ye, Z., Su, W., Lin, S.C., Shen, Y. and Wu, Q., Cytosporone B is anagonist for nuclear orphan receptor Nur77. Nature Chem. Biol. 4(9): 548-556, 2008.
20. Li, Q., Zhang, N., Zhang, D., Wang, Y., Lin, T., Wang, Y., Zhou, H., Ye, Z., Zhang, F., Lin, S.C. and Han, J., Determinants that control the distinct subcellular localization of p38α-PRAK and p38β-PRAK complexes. J. Biol. Chem. 283(16): 11014-23, 2008
21. Li, Q., Wang, X., Wu, X., Rui, Y., Liu, W., Wang, J., Wang, X., Liou,Y.-C., Ye, Z. and Lin, S.C., Daxx Cooperates with the Axin/HIPK2/p53 Complex to Induce Cell Death. Cancer Res. 67(1): 66-74, 2007
22. Lin, S.-C. and Li, Q.X., Axin bridges Daxx to p53. Cell Res., 17: 301-302, 2007, Apr.
23. Zou, H., Li, Q.*, Lin, S.C., Wu, Z., Han, J. and Ye, Z.*, Differential requirement of MKK4 and MKK7 in JNK activation by distinct scaffold proteins. FEBS Letters 581(2): 196–202, 2007.
24. Li, J., Li, Q.*, Xie, C., Zhou, H., Wang Y., Zhang, N., Shao, H., Chan, S.C., Peng, X., Lin, S.C. and Han, J. *, beta-actin is required for mitochondria clustering and ROS generation in TNF-induced, caspase-independent cell death. Journal of Cell Science 117: 4673-4680, 2004.
25. Rui, Y., Xu, Z., Lin, S., Li, Q., Rui, H., Luo, W., Zhou, H., Cheung, P., Wu, Z., Ye, Z., Li, P., Han, J. and Lin, S.-C., Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation. EMBO J. 23, 4583-4594, 2004, Nov 24.

荣誉、奖励及参加学术团体的情况:

“第四届复旦大学谈家桢基金生命科学九源奖学金”二等奖,2000年
教育部“新世纪优秀人才支持计划”入选者,2009年
福建省自然科学基金杰出青年基金获得者,2009年
福建省高等教育教学成果奖特等奖,2017年
国家高等教育教学成果奖二等奖,2018年
“宝钢优秀教师奖”,2019年
福建省高等教育教学成果奖特等奖,2020年