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个人简介

2015-至 今:中国科学院-马普学会计算生物学伙伴研究所,所长,研究员 2013-2014年:美国北卡大学教堂山分校,副教授(终身教职) 2007-2013年:美国北卡大学教堂山分校,助理教授(终身教职序列) 2002-2006年:美国麻省理工学院,博士后 1997-2002年:约翰霍普金斯大学医学院,生物化学系博士 1994-1997年:中国科学院生物物理研究所,生物化学系硕士 1992-1994年:清华大学,自动化系学士(第二学位) 1989-1994年:清华大学, 生物科学与技术系学士

研究领域

(1)阐析转录组RNA可变剪接的柔性调控以及由反向剪接生成的环状RNA功能:①从随机序列中系统性鉴定新的内含子剪接增强子ISE及与之特异结合的新剪接因子,发现ISE的活力受其在pre-mRNA上相对位置影响(Nat Struct Mol Biol 2012, 通讯作者);②系统性鉴定新的内含子剪接沉默子ISS及与之特异结合的新剪接因子,提出RNA-蛋白网络对剪接柔性调控的新模型(Nat Struct Mol Biol 2013, 共同通讯作者);③创建用于研究RNA剪接调控的新报告系统(Methods 2014,共同通讯作者);④发现剪接因子中的RNA识别结构域在进化中被大量复制(RNA 2014,通讯作者);⑤发现环形RNA的反式剪接成熟机制并证实其所含ORF能被翻译成蛋白质(RNA 2015,通讯作者);⑥揭示了环状RNA可作为编码蛋白的信使RNA新功能,并发现其翻译可由RNA的碱基编辑驱动(Cell Research 2017,通讯作者)。本结果被Science和Nature Review做了亮点评论。 (2)揭示癌细胞中可变剪接异化的专一性调控及其生物学功能:①发现选择性剪接在细胞周期中有着时序性调控,并影响着癌细胞的生长(eLife 2016, Cell Research 2016, 通讯作者);②发现剪接因子RBM4的抑癌机理并在全转录组鉴定出RBM4的靶点基因(Cancer Cell 2014,共同通讯作者),被评为2014年研究亮点;③发现细胞增值过程DAZAP1响应MEK/ERK信号转导通路对RNA剪接进行调控的机制(Nat Commun 2014,通讯作者);④利用癌症的致病基因组图谱(The Cancer Genome Atlas, TCGA),鉴定出癌症细胞中可变剪接发生异化的163个基因(Oncotargets 2015,共同通讯作者)。 (3)利用模块化合成系统设计构建特异性调控RNA剪接加工的人工蛋白质:①用PUF结构域和调控剪接的功能域来构建人工剪接因子,并成功矫正了癌细胞中的病理性剪接异化(Nat Methods 2009,通讯作者),被F1000评论推荐,并被Nature属下Science-Business Exchange (SciBX)专文评论为“This is a very elegant, imaginative and novel approach to build an artificial splicing factor from scratch”;②将PUF结构域和RNA内切酶组装成为人工RNA内切酶,从而特异性识别并降解线粒体编码的mRNA(Nat Commun 2013,通讯作者);③构建人工RNA内切酶,特异性降解强直性肌营养不良症中的毒性RNA,从而研发了此遗传疾病的一种新疗法(Mol Ther 2014,通讯作者);④整合PUF结构域特异识别所有RNA碱基的完善规则,使得PUF对RNA的特异结合,扩展到任意RNA序列(J Biol Chem 2011,通讯作者;FESBS J,共同通讯作者),其中J Biol Chem论文被评为当周最佳论文(Paper of the week);⑤设计构建了基于CRISPR-cas体系的mRNA翻译操纵系统(ACS Synth Biol 2015,共同通讯作者)。

近期论文

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Zhao YY, Mao MW, Zhang WJ, Wang J, Li HT, Yang Y, Wang Z*, Wu JW*. Expanding RNA binding specificity and affinity of engineered PUF domains. Nucleic Acids Research, 2018 May 18;46(9):4771-4782. Yang Y, Fan X, Mao M, Song X, Wu P, Zhang Y, Jin Y, Yang Y, Chen L, Wang Y, Wong CL , Xiao XG, Wang Z*. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell research, 2017 May;27(5):626-641. Hu J, Khodadadi-Jamayran A, Mao M, Shah K, Yang Z, Nasim MT, Wang Z*, Jiang H. AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors. Nature Communications, 2016 Nov 8;7:13347. Dominguez D, Tsai YH, Gomez N, Jha DK, Davis I and Wang Z*. A high-resolution transcriptome map of cell cycle reveals novel connections between periodic genes and cancer. Cell Research, 2016;26(8):946-962. Li R, Dong Q, Yuan X, Zeng X, Gao Y, Chiao C, Li H, Zhao X, Keles S, Wang Z*, Chang Q. Misregulation of Alternative Splicing in a Mouse Model of Rett Syndrome. Plos Genetics, 2016;12(6):e1006129. Dominguez D, Tsai YH, Weatheritt R, Wang Y, Blencowe B and Wang Z*. An Extensive Program of Periodic Alternative Splicing Linked to Cell Cycle Progression. Elife, 2016;5:e10288. Qi Y, Yu J, Han W, Fan X, Qian H, Wei H, Tsai YH, Zhao J, Zhang W, Liu Q, Meng S, Wang Y and Wang Z*. A splicing switch of TEAD4 regulates Hippo-YAP signaling pathway to inhibit tumor proliferation. Nature Communications, 2016;7:ncomms11840. Wang Y, Chen D, Qian H, Tsai YS, Shao S, Dominguez D and Wang Z. The splicing factor RBM4 controls apoptosis, proliferation, and migration to suppress tumor progression. Cancer Cell, 2014;26(3):374-389. Choudhury R, Ghose Roy S, Tsai YS, Tripathy A , Graves LM and Wang Z. The splicing activator DAZAP1 integrates splicing control into MEK/Erk regulated cell proliferation and migration. Nature Communications, 2014;5(2):3078. Matera AG* and Wang Z*. A day in the life of the spliceosome. Nature Reviews Molecular Cell Biology, 2014;15(2):108-121. Zhang W, Wang Y, Dong S, Choudhury R, Jin Y, Wang Z. Treatment of type 1 Myotonic Dystrophy by engineering site-specific RNA endonucleases that target (CUG)n repeats. Molecular Therapy, 2014;22(2):312-320. Wang Y, Xiao X, Zhang J, Choudhury R, Robertson A, Li K, Ma M, Burge CB and Wang Z. A complex network of factors with overlapping affinities represses splicing through intronic elements. Nature Structural & Molecular Biology, 2013;20(1):36-45. Choudhury R, Dominguez D, Wang Y and Wang Z. Engineering RNA endonucleases with customized sequence specificities. Nature Communications, 2012;3(4):1147. Wang Y, Ma M, Xiao XS and Wang Z. Intronic splicing enhancers, cognate splicing factors and context dependent regulation rules. Nature Structural & Molecular Biology, 2012;19(10):1044-1052. Wang Y, Cheong CG, Hall TM, Wang Z. Engineering splicing factors with designed specificities. Nature Methods, 2009;6(11):825-830. Xiao X, Wang Z, Jang M, Nutiu R, Wang ET, Burge CB. Splice site strength-dependent activity and genetic buffering by poly-G runs. Nature Structural & Molecular Biology, 2009;16(10):1094-1100. Wang Z, Nostrand EV, Xiao XS and Burge CB. General and specific functions of exonic splicing silencers in splicing Control. Molecular Cell, 2006;23(1):61-70. Wang Z, Rolish M, Yeo G, Tung V, Mawson M and Burge CB. Systematic identification and analysis of exonic splicing silencers. Cell, 2004;119(6):831-845.

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