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2017-12-08至2017-12-09 上海
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王兰 研究员

中科院上海生科院/上海交通大学医学院健康科学研究所

王兰 研究员

中科院上海生科院/上海交通大学医学院健康科学研究所

血液肿瘤学研究组长

研究方向
(1)白血病致病癌蛋白的翻译后修饰;
(2)表观遗传学及转录调控在血液肿瘤和造血干细胞中的作用;
(3)血液肿瘤和造血干细胞的代谢机制;
(4)RNA剪切在血液肿瘤和造血干细胞中的作用;

主要成果
(1)发现组蛋白乙酰转移酶p300能够特异的乙酰化白血病致病融合蛋白AML1-ETO上24号和43号赖氨酸,并揭示AML1-ETO融合蛋白的乙酰化控制白血病干细胞的自我更新和白血病的形成。(2)发现DNA结合抑制蛋白Id1是AML1-ETO融合蛋白的直接靶基因,并且阐明在白血病干细胞中特异的敲除Id1基因能够阻断白血病干细胞的自我更新和白血病的形成。(3)发现蛋白水解酶Caspase-3能够特异的诱导白血病致病融合蛋白AML1-ETO的降解, 并揭示可有效激活Caspase-3的二萜类化合物对白血病治疗有效。(4)发现中药复方有效成分硫化砷,靛玉红和丹参酮能够调控水通道蛋白AQP9的表达,并揭示AQP9可作为砷泵来控制细胞内的砷浓度,从而阐明复方有效成分通过提高细胞内砷浓度发挥协同作用。

学习经历
1998-2002 复旦大学生命科学院,生物学士
2002-2007 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

工作简历
2007-2013 美国纪念斯隆凯特琳癌症中心博士后
2013-2015 美国迈阿密大学生物化学与分子生物学系助理教授(tenure track)
2015    中科院上海生科院/上海交通大学医学院健康科学研究所 研究员

荣誊(证书,称号,会员)
2005:中国科学院优秀研究生奖
2006:上海血液学研究所优秀学生特等奖
2009:美国白血病淋巴瘤协会博士后奖
2010-2012:美国纽约州干细胞Fellow to Faculty 奖
2014:美国白血病研究基金奖
2014:美国迈阿密大学肿瘤协会奖
2014:美国Gabrielle Angel癌症基金奖
2015:美国癌症协会奖
2015:美国 Stanley J. Glaser 研究基金奖
2015:中组部第五批“青年千人计划”入选者
2016:国家“优秀青年”科学基金获得者
2016:国家人社部留学人员科技活动项目择优资助优秀类获得者

近期主要论文

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):2322-6.

Liu F, Wang L, Perna F, Nimer SD. Beyond transcription factors: how oncogenic signaling reshapes the epigenetic landscape.Nature Reviews Cancer. 2016 June; 16(6):359-72.

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.

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

Wang L, Hamard PJ, Nimer SD. PARP inhibitors: a treatment option for AML? Nature Medicine 2015 Dec 8;21(12):1393-4.

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):640-50. (* corresponding author)

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):3532-44.

Sun XJ, Man N, Tan Y, Nimer SD, Wang L. The role of histone acetyltransferase in normal and malignant hematopoiesis. Front Oncol. 2015 May 26;5:108.

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):1625-38.

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):93-7.

Hatlen MA, Wang L, Nimer SD. AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches. Front Med. 2012 Sep;6(3):248-62.

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):6544-52.

Wang L, Gural A, Sun X-J, et al. The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation. Science. 2011 Aug 5;333(6043):765-9.

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):283-94.

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):2812-21.

Zhang YW, Jiang XX, Chen QS, Shi WY, Wang L, et al. Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular signaling pathways. Experimental Hematology. 2010 Mar;38(3):191-201.

Wang L, Huang G, et al. Post-translational modifications of Runx1 regulate its activity in the cell. Blood Cells Mol Dis. 2009 Jul-Aug; 43(1):30-4.

Wang L, Zhou GB, et al. Dissection of mechanism of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci U S A. 2008; 105(12):4826-31.

Zhao WL, Wang L (co-first author), Liu YH, et al. Histone deacetylase inhibitor promotes rituximab-induced apoptosis in non-Hodgkin’s B-lymphoma cells by NF-kB-mediated Bcl-2/Bcl-XL downregulation and c-Myc degradation. Experimental Hematology. 2007; 35(12):1801-11.

Zhou GB, Kang H, Wang L(co-first author), Gao L, et al. 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; 109(8):3441-50.

Wang L, Zhao WL, et al. Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. Cell Death and Differentiation. 2007;14,306-317.

Wang L, Chen SJ. Monoclonal antibodies treat hematopoietic malignancies. Shanghai: Shanghai Science and Technology Press, 2006 pp.309-322.

Sun XJ, Wei J, Wu XY, Hu M, Wang L, et al. Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem. 2005; 280: 5261-71.

专著
申请和获权专利:
1. 发明人:陈赛娟,陈竺,王兰,周光飚,孙汉董
专利名称:毛萼乙素在制药中的应用 CN100370981C (2008-2-27)
2. 发明人:陈竺,陈赛娟,赵维莅,王兰,刘元华
专利名称:一种治疗B细胞淋巴瘤的药物组合中国 CN100346830C (2007-11-7)
3. 发明人:陈竺,陈赛娟,王兰,周光飚,刘萍
专利名称:中药复方制剂砷靛参及其制备方法和在制备抗肿瘤药物中的应用 200910051409.5 (2009-5-18)
4. 发明人:Nimer SD, Wang L.
US patent name: The novel therapeutic strategy for acute myeloid leukemia. SK2011-037-03 (2011)


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