刘文教授

发布者:张欧扬发布时间:2016-03-14浏览次数:64806

PI刘文,南强特聘教授、博士生导师,厦门大学药学院院长,福建省药物新靶点研究重点实验室主任

国家级青年人才项目入选者、国家基金委杰出青年基金、国家基金委优秀青年基金、福建省杰出青年科学基金获得者



    主要专注于癌症等重大疾病的表观遗传分子机制以及应用研究,在此领域取得了一系列具有重要意义的成果:是多项国际国内专利的持有人;发表多篇高水平研究论文,包括Nature,Cell,Cancer Cell,Developmental Cell, Molecular Cell,Science Advances, Nature Communications, PNAS,EMBO Journal等;在抗癌小分子K-80003方面的研究成果在国际上具有广泛的影响力,该小分子获得了美国FDA关于其在晚期结直肠癌中开展临床实验的批件并进入I期临床实验。主持多项课题:国家自然科学基金杰出青年基金,优秀青年基金,区域创新发展联合基金重点项目,NIH-NSFC生物医学合作研究项目,NSFC-RS中英人才项目,重大研究计划项目(培育项目),面上项目;科技部重大研究计划课题负责人;福建省自然科学基金“杰出青年科学基金”。取得多项荣誉,获得中国药学会-赛诺菲青年生物药物奖、福建省自然科学一等奖和福建省运盛青年科技奖。

  

获奖情况:

福建省科学技术奖一等奖,2023。

国家自然科学基金杰出青年科学基金2021

国家自然科学基金牛顿高级学者基金2018

福建省自然科学奖二等奖(参与),2018

厦门市科技进步三等奖(参与),2017

第二十四届运盛青年科技奖,2017

厦门大学科创竞赛优秀指导教师暨德贞社会课堂基金优秀指导教师奖,2017

第八届中国药学会-赛诺菲青年生物药物奖,2016

国家自然科学基金优秀青年科学基金2015

福建省自然科学基金杰出青年科学基金2015

厦门大学中国电信奖教金,2015

国家级青年人才项目,2013

福建省闽江学者特聘教授,2013

Susan G. Komen for the Cure Breast Cancer基金,2012

  

实验室简介:

        基因转录和剪接异常是导致癌症以及人类其它重大疾病的关键原因之一,而基因转录和剪接往往受到包括核受体,转录因子和表观遗传调控因子在内的关键因素精密调控。它们已被证实与癌症以及人类其它重大疾病密切关联,并已成为当今最前沿的药物靶点之一。探寻能有效抑制其活性和功能的小分子并开发新药物是当今生命医学研究最前沿的领域之一。然而,人们对于表观遗传调控因子调控基因转录和剪接的分子机制的认知还很匮乏,这严重制约了新药的开发。我们实验室充分结合分子生物学、细胞生物学、生物化学、药物化学、癌症生物学、高通量测序、质谱分析和生物信息学等多学科的技术,深入研究疾病中基因转录和剪接的潜在分子机制和调节通道,以期多角度地发现疾病诊疗新标志物,并以此为靶点探寻特异和有效的活性小分子,为开发新药物奠定坚实的理论和实验基础。

  

团队简介: 

1名教授,1名副教授,1名助理教授,博士后7名(其中合作培养3名),博士研究生8名,硕士研究生15名,其中专业生物信息技术人员2名,专业蛋白组学技术人员1名,专业计算机辅助药物设计人员2名。

  

目前开展的主要工作

表观遗传调控因子(包括非编码RNA)在乳腺癌、前列腺癌、结直肠癌和食道癌等癌症中的功能和分子机制研究;靶向表观遗传调控因子的药物研发研究。

  

代表性论文(第一或通讯作者论文):

1.  Shi-qiang Cao, Song-tao Xue, Wen-juan Li, Guo-sheng Hu, Zhi-gang Wu, Jian-cong Zheng, Shu-liang Zhang, Xiao Lin, Chun Chen*, Wen Liu*, Bin Zheng*. CircHIPK3 regulates fatty acid metabolism through miR-637/FASN axis to promote esophageal squamous cell carcinoma, Cell Death Discovery. 2024 Mar 2;10(1):110. doi: 10.1038/s41420-024-01881-z. Epub 2024 Mar 2.(*共同通讯作者)

2.  Song-tao Xue, Shi-qiang Cao, Jian-cheng Ding, Wen-juan Li, Guo-sheng Hu, Jian-cong Zheng, Xiao Lin, Chun Chen*, Wen Liu*, Bin Zheng*. LncRNA LUESCC promotes esophageal squamous cell carcinoma by targeting the miR-6785-5p/NRSN2 axis. Cellular and molecular life sciences.2024 Mar 8;81(1):121. doi: 10.1007/s00018-024-05172-9. Epub 2024 Mar 8. (*共同通讯作者)

3.  Xiao-Nan Wu, Jia-yuan Li, Qi He, Bo-qun Li, Yao-hui He, Xu Pan, Ming-yue Wang, Rui Sang, Jian-cheng Ding, Xiang Gao, Zhen Wu*, Wen Liu*. Targeting the PHF8/YY1 Axis Suppresses Cancer Cell Growth Through Modulation of ROS. PNAS. 2024 Jan 9;121(2):e2219352120. doi: 10.1073/pnas.2219352120. Epub 2024 Jan 2. (*共同通讯作者)

4.   Kuang Z, Guo K, Cao Y, Jiang M, Wang C, Wu Q, Hu G, Ao M, Huang M, Qin J, Zhao T, Lu S, Sun C, Li M, Wu T*, Liu W*, Fang M*. The novel CDK9 inhibitor, XPW1, alone and in combination with BRD4 inhibitor JQ1, for the treatment of clear cell renal cell carcinoma. Br J Cancer. 2023 Dec;129(12):1915-1929. doi: 10.1038/s41416-023-02464-y. Epub 2023 Oct 26. PMID: 37884683; PMCID: PMC10703862. (*共同通讯作者)

5.   Li WJ, Huang Y, Lin YA, Zhang BD, Li MY, Zou YQ, Hu GS, He YH, Yang JJ, Xie BL, Huang HH, Deng X*, Liu W*. Targeting PRMT1-mediated SRSF1 methylation to suppress oncogenic exon inclusion events and breast tumorigenesis. Cell Rep. 2023 Nov 28;42(11):113385. doi: 10.1016/j.celrep.2023.113385. Epub 2023 Nov 8. PMID: 37938975. (*共同通讯作者)

6.   Lu X, Peng L, Ding J, Li Y, Li Q, Rao M, Shu T, He X, Liu C, Ye J, Liu W*, You H*. A deregulated m6A writer complex axis driven by BRD4 confers an epitranscriptomic vulnerability in combined DNA repair-targeted therapy. Proc Natl Acad Sci U S A. 2023 Oct 10;120(41):e2304534120. doi: 10.1073/pnas.2304534120. Epub 2023 Oct 2. PMID: 37782793; PMCID: PMC10576145. (*共同通讯作者)

7.  Shi TT, Huang Y, Li Y, Dai XL, He YH, Ding JC, Ran T, Shi Y, Yuan Q, Li WJ*, Liu W*. MAVI1, an endoplasmic reticulum-localized microprotein, suppresses antiviral innate immune response by targeting MAVS on mitochondrion. Sci Adv. 2023 Sep;9(35):eadg7053. doi: 10.1126/sciadv.adg7053. Epub 2023 Sep 1. PMID: 37656786. (*共同通讯作者)

8.   Li D, Wang W, Liu B, Jin D, Wang Y, He G, Guo L, Liu W*, Li Y*. Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis. Cell Death Discov. 2023 Aug 10;9(1):294. doi: 10.1038/s41420-023-01593-w. PMID: 37563132; PMCID: PMC10415397. (*共同通讯作者)

9.   Chen X, Ding JC, Hu GS, Shu XY, Liu Y, Du J, Wen ZJ, Liu JY, Huang HH, Tang GH, Liu W. Estrogen-Induced LncRNA, LINC02568, promotes estrogen receptor-positive breast cancer development and drug resistance through both in trans and in cis mechanisms. Adv Sci (Weinh). 2023 Jul 5:e2206663. doi: 10.1002/advs.202206663. Epub ahead of print. PMID: 37404090. (通讯作者)

10. Ding N, You AB., Yang H, Hu GS, Lai CP, Liu W*, Ye F*.  A Tumor-suppressive Molecular Axis EP300/circRERE/miR-6837-3p/MAVS Activates Type I IFN Pathway and Antitumor Immunity to Suppress Colorectal Cancer.Clin Cancer Res. 2023 Jun 1, 29(11):2095-2109.doi: 10.1158/1078-0432.CCR-22-3836. PMID: 36951687; PMCID: PMC10233356.

11. Yi J, Wang L, Du J, Wang M, Shen H, Liu Z, Qin Y, Liu J, Hu G, Xiao R, Ding J, Chen X, Wang H, Huang H, Ouyang G*, Liu W*. ER-localized JmjC domain-containing protein JMJD8 targets STING to promote immune evasion and tumor growth in breast cancer. Dev Cell. 2023 Apr 6:S1534-5807(23)00131-4. doi: 10.1016/j.devcel.2023.03.015. Epub ahead of print. PMID: 37054705. (*共同通讯作者)

12. Yi J, Wang L, Hu GS, Zhang YY, Du J, Ding JC, Ji X, Shen HF, Huang HH, Ye F*, Liu W*. CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS. EMBO J. 2023 Apr 3:e112408. doi: 10.15252/embj.2022112408. Epub ahead of print. PMID: 37009655. (*共同通讯作者)

13.  Xia L, Yuan LZ, Hu YH, Liu JY, Hu GS, Qi RY, Zhang TY, Xiong HL, Zheng ZZ, Lin HW, Zhang JM, Yu C, Zhou M, Ma J, Cheng T, Chen RR, Guan Y, Xia NS*, Liu W*. A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19. Cell Mol Immunol. 2023 Apr;20(4):351-364. doi: 10.1038/s41423-023-00985-3. Epub 2023 Mar 2. PMID: 36864189; PMCID: PMC9979130. (*共同通讯作者)

14.  Hu GS, Zheng ZZ, He YH, Wang DC, Liu W. CPPA: A Web Tool for Exploring Proteomic and Phosphoproteomic Data in Cancer. J Proteome Res. 2023 Feb 3;22(2):368-373. doi: 10.1021/acs.jproteome.2c00512. Epub 2022 Dec 12. PMID: 36507870; PMCID: PMC9904288. (通讯作者)

15.  Zheng ZZ, Xia L, Hu GS, Liu JY, Hu YH, Chen YJ, Peng JY, Zhang WJ*, Liu W*. Super-enhancer-controlled positive feedback loop BRD4/ERα-RET-ERα promotes ERα-positive breast cancer. Nucleic Acids Res. 2022 Oct 14;50(18):10230-10248. doi: 10.1093/nar/gkac778. PMID: 36124682; PMCID: PMC9561272. (*共同通讯作者)

16.  Xiao RQ, Ran T, Huang QX, Hu GS, Fan DM, Yi J, Liu W. A specific JMJD6 inhibitor potently suppresses multiple types of cancers both in vitro and in vivo. Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2200753119. doi: 10.1073/pnas.2200753119. Epub 2022 Aug 15. PMID: 35969736; PMCID: PMC9407455. (通讯作者)

17. Songtao Xue, Bin Zheng, Shiqiang Cao, Jiancheng Ding, Guosheng Hu, Wen Liu*, Chun Chen*. Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis. Molecular Cancer. 2022. doi:10.1186/s12943-022-01539-3 (⃰ 共同通讯作者)

18. Xian Lin, Xianliang Ke, Xiaoqin Jian, Lin Xia, Yang Yang, Tianying Zhang, Hualong Xiong, Binghai Zhao, Wen Liu*, Quanjiao Chen*, Chong Tang*. Azacytidine targeting SARS-CoV-2 viral RNA as a potential treatment for COVID-19. Science Bulletin. 2022. doi:10.1016/j.scib.2022.02.002. (⃰ 共同通讯作者)

19. Zhaopeng Shi, Guifang Gan, Xiang Xu, Jieying Zhang, Yuan Yuan, Bo Bi, Xianfu Gao, Pengfei Xu, Wenbin Zeng, Jixi Li, Youqiong Ye, Aiwu Zhou, Naixia Zhang, Wen Liu*, Shuhai Lin*, Jun Mi*. Kynurenine derivative 3-HAA is an agonist ligand for transcription factor YY1. Journal of Hematology & Oncology. 2021 Sep 25;14(1):153.  (⃰ 共同通讯作者)

20. Wensheng Liu, Yinan Zhao, Xiaohua Liu, Xiaoya Zhang, Jiancheng Ding, Yang Li, Yingpu Tian, Haibin Wang, Wen Liu*, Zhongxian Lu*. A Novel Meiosis-Related lncRNA, Rbakdn, Contributes to Spermatogenesis by Stabilizing Ptbp2. Frontiers in Genetics. 2021 Oct 11; 12:752495. (⃰ 共同通讯作者)

21. Liu W, Xie L, He YH, Wu ZY, Liu LX, Bai XF, Deng DX, Xu XE, Liao LD, Lin W, Heng JH, Xu X, Peng L, Huang QF, Li CY, Zhang ZD, Wang W, Zhang GR, Gao X, Wang SH, Li CQ, Xu LY*, Liu W*, Li EM*. Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting. Nature Communications. 2021 Aug 16;12(1):4961.  (⃰ 共同通讯作者)

22. Lin XT, Zhuang SW, Chen X, Du J, Zhong LH, Ding JC, Wang L, Yi J, Hu GS, Tang GH, Luo X*, Liu W*, Ye F*. LncRNA ITGB8-AS1 functions as a ceRNA to promote colorectal cancer growth and migration through integrin-mediated focal adhesion signaling.Molecular Therapy.2022 Feb 2;30(2):688-702. (⃰ 共同通讯作者)

23. Xia L, Liu JY, Zheng ZZ, Chen YJ, Ding JC, Hu YH, Hu GS, Xia NS, Liu W. BRD4 inhibition boosts the therapeutic effects of epidermal growth factor receptor-targeted chimeric antigen receptor T cells in glioblastoma.Molecular Therapy. 2021 Oct 6;29(10):3011-3026. (通讯作者)

24. Jiang MX, Kuang ZJ, He YH, Cao Y, Yu TY, Chen JD*, Liu W*, Wang W*. SNAPIN regulates cell cycle progression to promote pancreatic β cell growth.Frontiers in Endocrinology. 2021 Jun 14;12:624309. (⃰ 共同通讯作者) 

25. Xia L, Zheng ZZ, Liu JY, Chen YJ, Ding JC, Hu GS, Liu SL, Luo WX, Xia NS, Liu W. Targeting triple negative breast cancer with combination therapy of epidermal growth factor receptor-targeted chimeric antigen receptor T cell and CDK7 inhibitor. Cancer Immunology Research. 2021 Jun;9(6):707-722.(通讯作者)

26. Li WJ, He YH, Yang JJ, Hu GS, Lin YA, Ran T, Peng BL, Xie BL, Huang MF, Gao X, Huang HH, Zhu HH, Ye F, Liu W. Profiling PRMT methylome reveals roles of hnRNPA1 arginine methylation in RNA splicing and cell growth. Nature Communications. 2021 Mar 29;12(1):1946.(通讯作者)

27. Shen HF, Zhang WJ, Huang Y, He YH, Hu GS, Wang L, Peng BL, Yi J, Li TT, Rong R, Chen XY, Liu JY, Li WJ, Ohgi K, Li SW, Rosenfeld MG, Liu W.The dual function of KDM5C in both gene transcriptional activation and repression promotes breast cancer cell growth and tumorigenesis. Advanced Science. 2021 Feb 18;8(9):2004635.(通讯作者)

28. Wang L, Yi j, Lu LY, Zhang YY, Wang L, Hu GS, Liu YC, Ding JC, Shen HF, Zhao FQ, Huang HH, Liu W. Estrogen-induced circRNA, circPGR, functions as a ceRNA to promote estrogen receptor-positive breast cancer cell growth by regulating cell cycle-related genes. Theranostics .2021 Jan 1; 11(4): 1732-1752.(通讯作者)

29. Xia L, Zheng ZZ, Liu JY, Chen YJ, Ding JC, Xia NX, Luo WX*, Liu W*. EGFR-targeted CAR-T cells are potent and specific in suppressing triple-negative breast cancer both in vitro and in vivo. Clinical & Translational Immunology 2020 May 3;9(5):e01135. (⃰ 共同通讯作者)

30. Peng BL, Li WJ, Ding JC, He YH, Ran T, Xie BL, Wang ZR, Shen HF, Xiao RQ, Gao WW, Ye TY, Gao X, Liu W. A hypermethylation strategy utilized by enhancer-bound CARM1 to promote estrogen receptor -dependent transcriptional activation and breast carcinogenesis. Theranostics2020 Feb 10; 10(8): 3451-3473. (通讯作者)

31. Tang GH, Chen X, Ding JC, Du J, Lin XT, Xia L, Lian JB, Ye F*, He XS*, Liu W*. LncRNA LUCRC Regulates Colorectal Cancer Cell Growth and Tumorigenesis by Targeting Endoplasmic Reticulum Stress Response. Frontiers in Genetics 2020 Jan 31;10:1409. ( ⃰ 共同通讯作者)

32. Ran T, Xiao RQ, Huang QX, Yuan HL, Lu T, Liu W. In Silico Discovery of JMJD6 Inhibitors for Cancer Treatment. ACS Med. Chem. Lett. 2019, Nov 19, 10(12):16091613. ( ⃰通讯作者)

33.  Lin BQ, An Y, Meng LY, Zhang HM, Song J, Zhu Z, Liu W*, Song YL*, Yang CY*. Control of CRISPR-Cas9 with small molecule-activated allosteric aptamer regulating sgRNAs. Chem. Commun. 2019 Oct 8;55(81):12223-12226. ( ⃰共同通讯作者)

34. Chen CH, Yang N, Zhang YC, Ding JC, Zhang WJ, Liu R, Liu W*, Chen CS*. Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers. Int. J. Biol. Sci.2019 Jun 10;15(8) :1733–1742. (共同通讯作者)

35. Li Y, Liu WS, Yi J, Kong SB, Ding JC, Zhao YN, Tian YP, Feng GS, Li CJ, Liu W*, Wang HB, Lu ZX*. The role of tyrosine phosphatase Shp2 in spermatogonial differentiation and spermatocyte meiosis.Asian Journal of Andrology.2020 Jan-Feb; 22(1):79–87.(共同通讯作者)

36. Ran T, Li WJ, Peng BL, Xie BL, Lu T, Lu S*, Liu W*. Virtual Screening with Structure-based Pharmacophore Model to Identify Small-molecule Inhibitors of CARM1. J Chem Inf Model .2019 Jan 28;59(1):522-534. (*共同通讯作者)

37. Gao WW, Xiao RQ, Zhang WJ, Hu YR, Peng BL, Li WJ, He YH, Shen HF, Ding JC, Huang QX, Ye TY, Li Y, Liu ZY, Ding R, Rosenfeld MG, Liu W. JMJD6 licenses estrogen receptor a-dependent enhancer and coding gene activation by modulating the recruitment of the CARM1/MED12 co-activator complex. Mol Cell 2018 Apr 19;70(2):340-357.e8. (通讯作者)

38. Wu XN, Shi TT, He YH, Wang FF, Sang R, Ding JC, Zhang WJ, Shu XY, Shen HF, Yi J, Gao X, Liu W. Methylation of transcription factor YY2 regulates its transcriptional activity and cell proliferation. Cell Discov. 2017 Oct 3;3:17035.通讯作者

39. Yi J, Shen HF, Qiu JS, Huang MF, Zhang WJ, Ding JC, Zhu XY, Zhou Y, Fu XD*, Liu W*. JMJD6 and U2AF65 co-regulate alternative splicing in both JMJD6 enzymatic activity dependent and independent manner. Nucleic Acids Res. 2017 Apr 7;45(6):3503-3518. ( ⃰共同通讯作者)

40. Zhang WJ, Wu XN, Shi TT, Xu HT, Yia J, Shen HF, Huang MF, Shu XY, Wang FF, Peng BL, Xiao RQ, Gao WW, Ding JC, Liu W. Regulation of transcription factor Yin Yang 1 by SET7/9-mediated lysine methylation. Sci Rep. 2016 Feb 23;6:21718.通讯作者

41. Gao WW, Xiao RQ, Peng BL, Xu HT, Shen HF, Huang MF, Shi TT, Yi J, Zhang WJ, Wu XN, Gao X, Lin XZ, Dorrestein PC, Rosenfeld MG*, Liu W*. Arginine methylation of HSP70 regulates retinoid acid-mediated RARβ2 gene activation. Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):E3327-36. ( ⃰共同通讯作者)

42. Liu W ⃰ #Ma Q#, Wong K, Li W, Ohgi K, Zhang J, Aggarwal AK, Rosenfeld MG ⃰. Brd4 and JMJD6-associated anti-Pause enhancers in regulation of transcriptional pause release. Cell. 2013 Dec 19;155(7):1581-1595. ( ⃰ 共同通讯作者#共同第一作者).

43. Liu W, Tanasa B, Tyurina OV, Zhou TY, Gassmann R, Liu WT, Ohgi KA, Benner C, Garcia-Bassets I, Aggarwal AK, Desai A, Dorrestein PC, Glass CK, Rosenfeld MG. PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression. Nature. 2010 Jul 22; 466(7305):508-12.第一作者

44. Zhou H #, Liu W#, Su Y, Wei Z, Liu J, Kolluri S.K., Wu H, Cao Y, Chen J, Wu Y, Yan T, Cao X, Gao W, Molotkov A, Jiang F, Li W.G., Lin B, Zhang H.P., Yu J, Luo S.P., Zeng JZ, Duester G, Huang PQ, Zhang XK NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling. Cancer Cell. 2010 Jun 15;17(6):560-73. ( #共同通讯作者)

  

招聘:本实验室诚招助理教授,博士后,博士及硕士研究生(长期有效)。

联系方式:

电话:0592-2881146

传真:0592-2881146

电子邮箱:w2liu@xmu.edu.cn