全体研究组长

王兰
博士 研究员 博士生导师

中科院肿瘤与微环境重点实验室,血液肿瘤学研究组组长

研究方向:血液肿瘤和造血干细胞的调控机制

电子邮件(E-mail):lwang@sibs.ac.cn

电话(Tel):021-54923267

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,研究员
2013-2015年:美国迈阿密大学,生物化学与分子生物学系,助理教授(tenure track)
2007-2013年:美国纪念斯隆凯特琳癌症中心博士后
2002-2007年:中科院上海生命科学院健康科学研究所,生物化学与分子生物学博士
1998-2002年:复旦大学生命科学院,生物学士

研究内容
造血干细胞恶性转化是血液肿瘤研究的关键问题,但是其机理尚不甚清楚。血液肿瘤干细胞与正常造血干细胞具有一个共同的特征:自我更新的能力,因此产生的子细胞具有增强的复制能力。增强的自我更新是血液肿瘤干细胞的一个显著特征,新的治疗策略应该特异地针对肿瘤干细胞异常的自我更新。在造血干细胞/白血病干细胞自我更新调控研究中,我们发现敲除DNA结合抑制蛋白Id1基因能够阻断造血干细胞/白血病干细胞的自我更新和白血病的形成并且Id1基因在3岁以下婴儿急性髓系白血病形成和成人急性髓系白血病形成中分别有促进和抑制的相反作用;另外,我们发现了Caspase-3与细胞自噬调控关键信号分子ULK1,mTOR作用并促进白血病发生的机理,研究结果为临床诊断和治疗提供了新的靶点。本课题组结合动物模型和生化机制分析造血干细胞恶性转化的分子机制,并最终把基础科研的发现转化成为癌症诊疗应用成果。

代表性论文(* 通讯作者)

  1. Kai Xue#, Ji-Chuan Wu#, Xi-Ya Li#, Ran Li#, Qun-ling Zhang, Jin-Jia Chang, Yi-Zhen Liu, Chun-Hui Xu, Jia-Ying Zhang, Xiao-Jian Sun, Juan J. Gu, Wei-Jian Guo*, Wang L*. Chidamide triggers BTG1-mediated autophagy and reverses the chemotherapy resistance in the relapsed/refractory B-cell lymphoma. Cell Death Dis 2021 Oct 1;12(10):900.
  2. Bing-Yi Chen#, Jun-Hong Song#, Cheng-Long Hu#, Shu-Bei Chen, Qunling Zhang, Chun-Hui Xu, Ji-Chuan Wu, Dan Hou, Dr. Ming Sun, Yuan-Liang Zhang, Na Liu, Peng-Cheng Yu, Ping Liu, Li-juan Zong, Jia-Ying Zhang, Ruo-fei Dai, Dr. Fei Lan, Qiuhua Huang, Sujiang Zhang, Stephen D Nimer, Prof. Zhu Chen, Prof. Sai-Juan Chen, Xiao-Jian Sun*, Wang L*. SETD2 deficiency accelerates MDS-associated leukemogenesis via S100a9 in NHD13 mice and predicts poor prognosis in MDS. Blood 2020 Jun 18;35(25):2271-2285.
  3. Meng-Meng Zhang#, Na Liu#, Yuan-Liang Zhang#, Bowen Rong, Xiao-Lin Wang, Chun-Hui Xu, Yin-Yin Xie, Shuhong Shen, Jiang Zhu, Stephen D. Nimer, Zhu Chen, Sai-Juan Chen, Robert G. Roeder, Fei Lan, Wang L*, Qiu-Hua Huang*, Xiao-Jian Sun*. Destabilization of AETFC through C/EBPα-mediated repression of LYL1 contributes to t(8,21) leukemic cell differentiation. Leukemia 2019 Jul;33(7):1822-1827.
  4. Liu Na#, Song Junhong#, Xie Yangyang#, Wang Xiaolin, Rong Bowen, Man Na, Zhang Mengmeng, Zhang Qunling, Gao Feifei, Du Meirong, Zhang Ying, Shen Jian, Xu Chunhui, Hu Chenglong, Wu Jichuan, Liu Ping, Zhang Yuanliang, Xie Yinyin, Liu Ping, Huang Jinyan, Huang Qiuhua, Lan Fei, Shen Shuhong, Nimer Stephen D, Chen Zhu, Chen Saijuan, Roeder Robert G*, Wang L*, Sun Xiaojian*. Different roles of E proteins in t(8;21) leukemia: E2-2 compromises the function of AETFC and negatively regulates leukemogenesis. Proc Natl Acad Sci U S A 2019 Jan 15;116(3):890-899.
  5. Na Man, Yurong Tan, Xiaojian Sun, Fan Liu, Guoyan Cheng, Sarah Greenblatt, Camilo Martinez, Daniel L. Karl, Koji Ando, Ming Sun, Dan Hou, Bingyi Chen, Mingjiang Xu, Fengchun Yang, Zhu Chen, Saijuan Chen, Stephen D. Nimer*, Wang L*. Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1 dependent manner. Blood 2017 May 18;129(20):2782-2792.
  6. Na Man, Sun XJ, Tan Y, Cao M, Liu F, Cheng G, Hatlen M, Xu H, Shah R, Huang G, Zhou Y, Sheng M, Yang F, Benezra R, Nimer SD*, Wang L*. Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin. Blood 2016 May 12;127(19):2322-2326.
  7. Wang L, Hamard PJ, Nimer SD. PARP inhibitors: a treatment option for AML? Nat Med 2015 Dec;21(12):1393-1394.
  8. Wang L*, Man N, Sun XJ, Tan Y, Cao MG, Liu F, Hatlen M, Xu H, Huang G, Mattlin M, Mehta A, Rampersaud E, Benezra R, Nimer SD. Regulation of AKT signaling by Id1 controls t(8,21) leukemia initiation and progression. Blood 2015 Jul 30;126(5):640-650. (* corresponding author)
  9. Sun XJ, Man N, Tan Y, Nimer SD, Wang L*. The Role of Histone Acetyltransferases in Normal and Malignant Hematopoiesis. Front Oncol 2015 May 26;5:108.
  10. Wang L, Gural A, Sun XJ, Zhao X, Perna F, Huang G, Hatlen MA, Vu L, Liu F, Xu H, Asai T, Xu H, Deblasio T, Menendez S, Voza F, Jiang Y, Cole PA, Zhang J, Melnick A, Roeder RG, Nimer SD. The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation. Science 2011 Aug 5;333(6043):765-769.
  11. Wang L, Huang G, Zhao X, Hatlen MA, Vu L, Liu F, Nimer SD. Post-translational modifications of Runx1 regulate its activity in the cell. Blood Cells Mol Dis 2009 Jul-Aug;43(1):30-34.
  12. Zhao WL, Wang L (co-first author), Liu YH, Yan JS, Leboeuf C, Liu YY, Wu WL, Janin A, Chen Z, Chen SJ. Combined effects of histone deacetylase inhibitor and rituximab on non-Hodgkin's B-lymphoma cells apoptosis. Exp Hematol 2007 Dec;35(12):1801-1811.
  13. Zhou GB, Kang H, Wang L (co-first author), Gao L, Liu P, Xie J, Zhang FX, Weng XQ, Shen ZX, Chen J, Gu LJ, Yan M, Zhang DE, Chen SJ, Wang ZY, Chen Z. Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8,21) leukemia in vitro and in vivo. Blood 2007 Apr 15;109(8):3441-3450.
  14. Wang L, Zhao WL, Yan JS, Liu P, Sun HP, Zhou GB, Weng ZY, Wu WL, Weng XQ, Sun XJ, Chen Z, Sun HD, Chen SJ. Eriocalyxin B induces apoptosis of t(8,21) leukemia cells through NF-kappaB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. Cell Death Differ 2007 Feb;14(2):306-317.
  15. Dian-Jia Liu#, Fan Zhang#, Yi Chen#, Yi Jin, Yuan-Liang Zhang, Shu-Bei Chen, Yin-Yin Xie, Qiu-Hua Huang, Wei-Li Zhao, Wang L, Peng-Fei Xu, Zhu Chen, Sai-Juan Chen, Bing Li, Aijun Zhang, Xiao-Jian Sun*. Setd2 knockout zebrafish is viable and fertile: differential and developmental stress-related requirements for Setd2 and histone H3K36 trimethylation in different vertebrate animals. Cell Discov 2020 Oct 20;6:72.
  16. Ye Xu, Na Man, Daniel Karl, Concepcion Martinez, Fan Liu, Jun Sun, Camilo Jose Martinez, Gloria Mas Martin, Felipe Beckedorff, Fan Lai, Jingyin Yue, Alejandro Roisman, Sarah Greenblatt, Stephanie Duffort, Wang L, Xiaojian Sun, Maria Figueroa, Ramin Shiekhattar*, Stephen Nimer*. TAF1 plays a critical role in AML1-ETO driven leukemogenesis. Nat Commun 2019 Oct 29;10(1):4925.
  17. Zhang YL, Sun JW, Xie YY, Zhou Y, Liu P, Song JC, Xu CH, Wang L, Liu D, Xu AN, Chen Z, Chen SJ, Sun XJ*, Huang QH*. Setd2 deficiency impairs hematopoietic stem cell self-renewal and causes malignant transformation. Cell Res 2018 Apr;28(4):476-490.
  18. G Cheng, F Liu, T Asai, F Lai, N Man, H Xu, S Chen, S Greenblatt, P-J Hamard, K Ando, X Chen, L Wang, C Martinez, M Tadi, Wang L, M Xu, F-C Yang, R Shiekhattar, S D Nimer. Loss of p300 accelerates MDS-associated leukemogenesis. Leukemia 2017 Jun;31(6):1382-1390.
  19. Li J, He F, Zhang P, Chen S, Shi H, Sun Y, Guo Y, Yang H, Man N, Greenblatt S, Li Z, Guo Z, Zhou Y, Wang L, Morey L, Williams S, Chen X, Wang QT, Nimer SD, Yu P, Wang QF, Xu M, Yang FC. Loss of Asxl2 leads to myeloid malignancies in mice. Nat Commun 2017 Jun 8;8:15456.
  20. Tang YC, Yuwen H, Wang K, Bruno PM, Bullock K, Deik A, Santaguida S, Trakala M, Pfau SJ, Zhong N, Huang T, Wang L, Clish CB, Hemann MT, Amon A. Aneuploid Cell Survival Relies upon Sphingolipid Homeostasis. Cancer Res 2017 Oct 1;77(19):5272-5286.
  21. Liu F, Wang L, Perna F, Nimer SD. Beyond transcription factors: how oncogenic signaling reshapes the epigenetic landscape. Nature Reviews Cancer 2016 Jun;16(6):359-372.
  22. Shirakawa K, Wang L, Man N, Maksimoska J, Sorum AW, Lim HW, Lee IS, Shimazu T, Newman JC, Schroder S, Ott M, Marmorstein R, Meier J, Nimer S, Verdin E. Salycylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity. Elife 2016 May 31;5.
  23. Megan A. Hatlen, Arora K, Vacic V, Grabowska E, Liao W, Riley-Gillis B, Oschwald D, Wang L, Joergens J, Shih A, Rapaport F, Gu S, Voza F, Asai T, Neel B, Kharas M, Gonen M, Levine R, Nimer SD. Integrative analysis of the mutational landscape of mouse and human AML identifies functionally relevant leukemia disease alleles. J Exp Med 2016 Jan 11;213(1):25-34.
  24. Liu F, Cheng G, Hamard PJ, Greenblatt S, Wang L, Man N, Perna F, Xu H, Tadi M, Luciani L, Nimer SD. Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis. J Clin Invest 2015 Sep;125(9):3532-3544.
  25. Vu L, Perna F, Wang L, Voza F, et al. PRMT4 Blocks Myeloid Differentiation by Assembling a Methyl-RUNX1-Dependent Repressor Complex. Cell Reports 2013 Dec 26;5(6):1625-1638.
  26. Sun X-J, Wang Z, Wang L, Jiang Y, et al. A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis. Nature 2013 Aug 1;500(7460):93-97.
  27. Hatlen MA, Wang L, Nimer SD. AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches. Front Med 2012 Sep;6(3):248-262.
  28. Huang G, Zhao X, Wang L, Elf S, et al. The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood 2011 Dec 15;118(25):6544-6552.
  29. Liu F, Zhao X, Perna F, Wang L, Koppikar P, et al. JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation. Cancer Cell 2011 Feb 15;19(2):283-294.
  30. Perna F, Gurvich N, Hoya-Arias R, Abdel-Wahab O, Levine RL, Asai T, Voza F, Menendez S. Wang L, et al. Depletion of L3MBTL1 promotes the erythroid differentiation of human hematopoietic progenitor cells: possible role in 20q- polycythemia vera. Blood 2010 Oct 14;116(15):2812-2821.
  31. Zhang YW, Jiang XX, Chen QS, Shi WY, Wang L, et al. Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular signaling pathways. Exp Hematol 2010 Mar;38(3):191-201.
  32. Wang L, Zhou GB, Liu P, Song JH, Liang Y, Yan XJ, Xu F, Wang BS, Mao JH, Shen ZX, Chen SJ, Chen Z. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci U S A 2008 Mar 25;105(12):4826-4831.
  33. Wang L, Chen SJ. Monoclonal antibodies treat hematopoietic malignancies. Shanghai: Shanghai Science and Technology Press 2006 pp.309-322.
  34. Sun XJ, Wei J, Wu XY, Hu M, Wang L, Wang HH, Zhang QH, Chen SJ, Huang QH, Chen Z. Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem 2005 Oct 21;280(42):5261-5271.