王跃祥

王跃祥

博士
肿瘤演变与转化医学研究组组长

邮箱: yxwang76@sinh.ac.cn

电话: +86-21-54923278

所属部门: 中国科学院肿瘤与微环境重点实验室

个人简历

2017-至  今:中国科学院上海营养与健康研究所,研究员
2015-2016年:中国科学院上海生命科学研究院/上海交通大学医学院健康科学研究所-上海长征医院联合转化医学中心,研究员
2007-2015年:美国哈佛大学医学院/布莱根妇女医院病理系博士后、高级研究科学家、讲师
1999-2007年:复旦大学上海医学院分子医学教育部重点实验室助教、讲师、副教授
2001-2007年:复旦大学上海医学院,生物化学与分子生物学,博士
1994-1999年:上海医科大学,药理学,学士
  

研究方向

消化道肿瘤恶性演变的分子机制及治疗策略

研究内容

  肿瘤是一类由基因突变导致的遗传性疾病,本实验室主要解析人类恶性肿瘤演变的分子遗传学机制,为这些致死性肿瘤的早期诊断和治疗提供新型策略。主要的研究方向有:
  1. 肉瘤(间叶细胞来源恶性肿瘤)演变的分子机制;
  2. KRAS突变癌(胰腺癌、肺癌等)演变的分子机制;
  3. 整合多组学大数据分析与人工智能;
  4. 新型诊断试剂及抗肿瘤药物的研制。
  

代表论著(#第一作者,*通讯作者)

1. Wang S, Xiong Y, Luo Y, Shen Y, Zhang F, Lan H, Pang Y, Wang X, Li X, Zheng X, Lu X, Liu X, Cheng Y, Wu T, Dong Y, Lu Y, Cui J, Jia X, Yang S, Wang L*, Wang Y*. Genome-wide CRISPR screens identify PKMYT1 as a therapeutic target in pancreatic ductal adenocarcinoma. EMBO Mol Med 2024; doi: 10.1038/s44321-024-00060-y.

2. Zheng X#, Luo Y#, Xiong Y#, Liu X, Zeng C, Lu X, Wang X, Cheng Y, Wang S, Lan H, Wang K, Weng Z, Bi W, Gan X, Jia X, Wang L*, Wang Y*. Tumor cell-intrinsic SETD2 inactivation sensitizes cancer cells to immune checkpoint blockade through the NR2F1-STAT1 pathway. J Immunother Cancer 2023;11(12):e007678.

3. Li K#, Zheng X#, Tang H#, Zang Y#, Zeng C, Liu X, Shen Y, Pang Y, Wang S, Xie F, Lu X, Luo Y, Li Z, Bi W, Jia X, Huang T, Wei R, Huang K, Chen Z, Zhu Q, He Y, Zhang M, Gu Z, Xiao Y, Zhang X, Fletcher J, Wang Y*. E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non-small cell lung cancer. J Exp Med 2021;218(8):e20210151.

4. Lu X#, Pang Y#, Cao H#, Liu X#, Tu L, Shen Y, Jia X, Lee JC, Wang Y*. Integrated screens identify CDK1 as a therapeutic target in advanced gastrointestinal stromal tumors. Cancer Res 2021;81(9):2481-2494.

5. Pang Y#, Xie F#, Cao H#, Wang C#, Zhu M, Liu X, Lu X, Huang T, Shen Y, Li K, Jia X, Li Z, Zheng X, Wang S, He Y, Wang L, Fletcher J*, Wang Y*. Mutational inactivation of mTORC1 repressor gene DEPDC5 in human gastrointestinal stromal tumors. Proc Natl Acad Sci U S A 2019;116(45):22746-22753. (Direct submission)
(highlighted by MedicalXpress, The Medical News, Genome Web, Science Codex, Asia-Pacific Biotech News)

6. Cheng Y#, Jia X#, Wang Y*. Advance of non-receptor tyrosine kinase targets in the treatment of gastrointestinal stromal tumor. Cancer 2022;42(10):700-707.

7. Liu X#, Li Z#, Wang Y*. Advances in targeted therapy and immunotherapy for pancreatic cancer. Adv Biology 2021;5(3):e1900236.

8. Zhou Y#, Zeng C#, Sun X#, Zhang J#, Qu H#, Zhang X#, Zhou Y#, Liu Z#, Wu X#, Wu X#, Jiao X, Shen L, Zhou Y*, Wang Y*, Li J*. Activity of anlotinib in the second-line therapy of metastatic gastrointestinal stromal tumors: a prospective, multicenter, in vitro study. Oncologist 2023;28(4):e191-e197.

9. Lv Y#, Tang W#, Zhang Z#, Lin Q#, Luo Y#, Zheng P, Li K, Jia X, Pang Y, Ji M, Feng Q, He G, Wang Y*, Xu J*. Cullin-9/p53 mediates HNRNPC degradation to inhibit erastin-induced ferroptosis and is blocked by MDM2 inhibition in colorectal cancer. Oncogene 2022;41(23):3210-3221.

10. Zeng C#, Zhu L#, Jia X#, Pang Y#, Li Z#, Lu X, Xie F, Duan L, Wang Y*. Spectrum of activity of dasatinib against mutant KIT kinases associated with drug-sensitive and drug-resistant gastrointestinal stromal tumors. Gastric Cancer 2020;23(5):837-847.

11. Li Z#, Shao C#, Liu X, Lu X, Jia X, Zheng X, Wang S, Zhu L, Li K, Pang Y, Xie F, Lu Y, Wang Y*. Oncogenic ERBB2 aberrations and KRAS mutations cooperate to promote pancreatic ductal adenocarcinoma progression. Carcinogenesis 2020;41(1):44-55.

12. Guan L, Li Z, Xie F, Pang Y, Zhang C, Tang H, Zhang H, Chen C, Zhan Y, Zhao T, Jiang H, Jia X, Wang Y*, Lu Y*. Oncogenic and drug-sensitive RET mutations in human epithelial ovarian cancer. J Exp Clin Cancer Res 2020;39(1):53.

13. Chinese expert consensus on the small gastrointestinal stromal tumors. Chinese Clinical Oncology 2020;25(4):352-358.

14. Wang YX*, Fletcher JA*. Cell cycle and dystrophin dysregulation in GIST. Cell Cycle 2015;14(17):2713-2714.

15. Wang YX, Marino-Enriquez A, Bennett RR, Zhu MJ, Shen YP, Eilers G, Lee JC, Fletcher BS, Gu ZZ, Fox EA, Antonescu CR, Fletcher CDM, Guo XQ, Raut CP, Demetri GD, van de Rijn M, Ordog T, Kunkel LM, Fletcher JA. Dystrophin is a tumor suppressor in human cancers with myogenic programs. Nat Genet 2014;46(6):601-606.
(highlighted by "Laboratory Investigation", "Modern Pathology" and "BioWorld Today", featured in "Cancer Discovery" Research Watch and selected as one of the most popular stories on nature.com)

16. Serrano C#, Wang YX#, Marino-Enriquez A, Lee JC, Ravegnini G, Morgan JA, Bertagnolli MM, Beadling C, Demetri GD, Corless CL, Heinrich MC, Fletcher JA. KRAS and KIT gatekeeper mutations confer polyclonal primary imatinib resistance in GIST: Relevance of concomitant PI3K/AKT dysregulation. J Clin Oncol 2015;33(22):e93-96. (#Both authors contributed equally)

17. Song Z#, Wang S#, Lu L#, Xu J, Zhou Q, Lu W, Tong H, Zhang Y, Liu W, Wang Z, Li W, You Y, Zhang C, Guo X, Luo R, Hou Y, Wang C, Wang Y, Sun L*, Huang H*, Zhou Y*. Lipidomics and transcriptomics differ liposarcoma differentiation characteristics that can be altered by pentose phosphate pathway intervention. Metabolites 2022;12(12):1227.

18. Zhang X, Mao T, Zhang B, Xu H, Cui J, Jiao F, Chen D, Wang Y, Hu J, Xia Q, Li S, Yue M, Ma J, Yao J, Wang Y, Zhang X, Chen S, Bai Y, Wang Y, Zhang X, Liu Q, Sun Y, Fu D, Liu Y, Xiong L, Wang L. Characterization of DNA damage response deficiency in pancreatic cancer patients from China. Cancer Commun (Lond) 2022;42(1):70-74.

19. Heinrich M, Patterson J, Beadling C, Wang Y, Debiec-Rychter M, Dewaele B, Corless CL, Duensing A, Raut CP, Rubin B, Ordog T, van de Rijn M, Call J, Mühlenberg T, Fletcher JA, Bauer S. Genomic aberrations in cell cycle genes predict progression of KIT-mutant gastrointestinal stromal tumors. Clin Sarcoma Res 2019;9:3.

20. Schaefer IM, Wang Y, Liang CW, Bahri N, Quattrone A, Doyle L, Marino-Enriquez A, Lauria A, Zhu M, Debiec-Rychter M, Grunewald S, Hechtman JF, Dufresne A, Antonescu CR, Beadling C, Sicinska ET, van de Rijn M, Demetri GD, Ladanyi M, Corless CL, Heinrich MC, Raut CP, Bauer S, Fletcher JA. MAX inactivation is an early event in GIST development that regulates p16 and cell proliferation. Nat Commun 2017;8:14674.

21. Chen W, Kuang Y, Qiu HB, Cao Z, Tu Y, Sheng Q, Eilers G, He Q, Li HL, Zhu M, Wang Y, Zhang R, Wu Y, Meng F, Fletcher JA, Ou WB. Dual targeting of Insulin Receptor and KIT in imatinib-resistant gastrointestinal stromal tumors. Cancer Res 2017;77(18):5107-5117.

22. Wang Y, Yan X, Mi S, Li Z, Wang Y, Zhu H, Sun X, Zhao B, Zhao C, Zou Y, Hu K, Ding X, Sun A, Ge J. Naoxintong attenuates ischaemia/reperfusion injury through inhibiting NLRP3 inflammasome activation. J Cell Mol Med 2017;21(1):4-12.

23. Wang Q, Liu F, Wang B, Zou F, Chen C, Liu X, Wang A, Qi S, Wang W, Qi Z, Zhao Z, Hu Z, Wang W, Wang L, Zhang S, Wang Y, Liu J, Liu Q. Discovery of N-(3-((1- Isonicotinoylpiperidin-4-yl)oxy)-4-methylphenyl)-3-(trifluoromethyl)benzamide(CHMFL-KIT-110) as a Selective, Potent, and Orally Available Type II c-KIT Kinase Inhibitor for Gastrointestinal Stromal Tumors. J Med Chem 2016;59(8):3964-3979.

24. Maynard MA, Marino-Enriquez A, Fletcher JA, Dorfman DM, Raut CP, Yassa L, Guo C, Wang Y, Dorfman C, Feldman HA, Frates MC, Song H, Jugo RH, Taguchi T, Hershman JM, Larsen PR, Huang SA. Thyroid hormone inactivation in gastrointestinal stromal tumors. N Engl J Med 2014;370(14):1327-1334.

25. Marino-Enriquez A, Ou WB, Cowley G, Luo B, Jonker AH, Mayeda M, Okamoto M, Eilers G, Czaplinski JT, Sicinska E, Wang Y, Taguchi T, Demetri GD, Root DE, Fletcher JA. Genome-wide functional screening identifies CDC37 as a crucial HSP90-cofactor for KIT oncogenic expression in gastrointestinal stromal tumors. Oncogene 2014;33(14):1872-1876.

26. Lynn M, Wang Y, Slater J, Shah N, Conroy J, Ennis S, Morris T, Betts DR, Fletcher JA, O'Sullivan MJ. High-resolution genome-wide copy-number analyses identify localized copy-number alterations in Ewing sarcoma. Diagn Mol Pathol 2013;22(2):76-84.

27. Ravegnini G, Marino-Enriquez A, Slater J, Eilers G, Wang Y, Zhu M, Nucci MR,George S, Angelini S, Raut CP, Fletcher JA. MED12 mutations in leiomyosarcoma and extrauterine leiomyoma. Mod Pathol 2013;26(5):743-749.

28. Lee CH, Ou WB, Marino-Enriquez A, Zhu M, Mayeda M, Wang Y, Guo X, Brunner AL, Amant F, French CA, West RB, McAlpine JN, Gilks CB, Yaffe MB, Prentice LM,McPherson A, Jones SJ, Marra MA, Shah SP, van de Rijn M, Huntsman DG, Dal Cin P, Debiec-Rychter M, Nucci MR, Fletcher JA. 14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma. Proc Natl Acad Sci U S A 2012;109(3):929-934.

29. Wang YX, Qian LX, Dong YX, Yao LL, Gui YH, Zhong TP, Song HY. Bone Morphogenetic Protein-2 acts upstream of Myocyte-specific Enhancer Factor 2A to control embryonic cardiac contractility. Cardiovasc Res 2007;74(2):290-303.

30. Wang YX, Qian LX, Jiang Q, Dong YX, Gui YH, Zhong TP, Song HY. Myocyte-specific enhancer factor 2A is essential for zebrafish posterior somite development. Mech Dev 2006;123(10):783-791.

31. Wang YX, Qian LX, Yu Z, Jiang Q, Dong YX, Liu XF, Yang XY, Zhong TP, Song HY. Requirements of myocyte-specific enhancer factor 2A in zebrafish cardiac contractility. FEBS Lett 2005;579(21):4843-4850.

32. Wang Y, Zhong T, Qian L, Dong Y, Jiang Q, Tan L, Song H. Wortmannin induces zebrafish cardia bifida through a mechanism independent of phosphoinositide 3-kinase and myosin light chain kinase. Biochem Biophys Res Commun 2005;331(1):303-308. (Cover Photo)

33. Wang YX, Song HY. Developmental genetics of zebrafish cardiovascular systems. Section Genet Foreign Med Sci 2004;27(4):220-223.

34. Wang YX, Yang J, Ma CG, Yang XY, Song HY. VEGF121 cDNA gene transfer and expression in Vitro. Prog Biochem Biophys 2003;30(4):612-616.

35. Wang YX, Guan XQ, Yang J, Mo W, Song HY. Molecular Cloning, Expression and characterization of recombinant human vascular endothelial growth factor 121. Prog Biochem Biophys 2002;29(3):444-448.