王兰 - 中国科学院上海营养与健康研究所 -

个人简介

2017－至今中国科学院上海营养与健康研究院，研究员 2015－2016 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 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 美国纪念斯隆凯特琳癌症中心博士后 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 1998－2002 复旦大学生命科学院，生物学士

研究领域

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。 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；

近期论文

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Bing-Yi Chen, Jun-Hong Son, 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 predicts poor prognosis in MDS and accelerated MDS-associated leukemogenesis via S100a9. Blood. 2020 June 18,35(25):2271-2285. 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 Feb 12,33:1822-1827. Liu Na, Song Junhong, Xie Yangyang, Wang Xiao Lin, Rong Bowen, Man Na, Zhang Meng Meng, Zhang Qunling, Gao Fei Fei, Du Mei Rong, Zhang Ying, Shen Jian, Xu Chun Hui, Hu Cheng Long, Wu Ji Chuan, Liu Ping, Zhang Yuan Liang, Xie Yin Yin, Liu Ping, Huang Jin Yan, Huang Qiu Hua, Lan Fei, Shen Shuhong, Nimer Stephen D, Chen Zhu, Chen Sai Juan, Roeder Robert G*, Wang L*, Sun Xiao Jian*. Proc Natl Acad Sci U S A. 2019 Jan 15,116(3):890-899. Man N, Tan Y, Sun XJ, Liu F, Cheng G, Greenblatt S, Martinez C, Karl D, Ando K, Sun M, Hou D, Chen B, Xu M, Yang F, Chen Z, Chen SJ, Nimer SD, 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. Man N, 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. Wang L, Hamard PJ, Nimer SD. PARP inhibitors: a treatment option for AML? Nature Medicine. 2015 Dec 8,21(12):1393-1394. 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. 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. 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. 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. 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. 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. 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. 2007,109:3441-3450. 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. 2007,14:306-317.