非常牛人：张毅--科学观察评最新10大顶尖作者

汤姆森科技信息集团旗下《科学观察》(Science Watch)对来自其 Essential Science Indicators（基本科学指标）的数据做了分析，筛选出了2002-2006年期间分子生物学和遗传学领域最具影响力的1300篇高影响力论文，《科学观察》选出了被提及次数最多的10大机构、高影响力论文的数量最多的25位研究人员和顶尖10大期刊。高影响力论文的数量最多Top 10的科学家里居然有一个中国人的名字----Yi Zhang！排在第7位。2002-2006年期间分子生物学和遗传学领域最具影响力的1300篇高影响力论文有Yi Zhang的11篇高影响力论文。

　　

    不是最早是否源自“金榜提名”，国人对排名有特别的热忱。从小学读数起，“排第几名啊”就已经成为无数学生心中的痛。工作了也难逃其害。高校排名，实验室排名，明星人物收入排名，流行音乐排名榜，更有英国人胡润，这个学中文的小子在福布斯做中国区调查员时每制作出一张中国大陆富豪排行榜，只能从《福布斯》杂志获得几千元的稿费----自己推出胡润百富榜却能为他带来每年超过千万元的收入......连本来籍籍无名的小网站Alexa排名也被投机分子利用来招摇撞骗在国内狠火了一把（虽然有人民网等公信媒体多次揭发，至今照样有人拿这破Alexa排名忽悠你傻呢）。反正，甭管是谁，甭管他什么水平，只要有人排表有数据就能引人注意。

    不过生物通今天在这里介绍的可绝不是一般的排名。这是汤姆森科技信息集团旗下《科学观察》(Science Watch)对来自其 Essential Science Indicators（基本科学指标）的数据做了分析，筛选出了2002-2006年期间分子生物学和遗传学领域最具影响力的1300篇高影响力论文，《科学观察》选出了被提及次数最多的10大机构、高影响力论文的数量最多的25位研究人员和顶尖10大期刊。这样的分析是《科学观察》所特有的，它使用独特的引用数据来提供当今最重要的科学领域的排名。

    汤姆森集团你不熟悉的话，做科研的你一定不会不知道SCI。科学引文索引SCI就是汤姆森集团旗下一个数据库。科学引文索引SCI的初衷是：一项研究工作的质量是由它对所在领域的影响程度来衡量的，一篇文章的引用率越高，它的影响力就会越大。由于有了引文索引，发展出科学计量学中著名的引文分析方法，定量地研究社会的科学能力，科学前沿发展趋势，科学活动的水平，科学论文的质量，科学机构与人才的评估。SCI由最初的印刷出版物，经历了光盘版，发展为目前的网络版（Web of Science），用户可以无缝链接到世界最重要的近9000种核心期刊，回溯自 1900 年以来的科学引文。全球目前有900万研究人员在使用Web of Science。这个机构统计出来的结果，显然应该是很可靠的。虽然以高影响力论文的数量多少并不能作为评价学术机构和研究人员的唯一参考，但是能入选全球1%顶尖影响力的论文本身也能证明其价值。

    我们回到这3个根据引用文献影响率选出的分子生物学和遗传学领域的Top 10排名。Top 10的机构显然是难觅中国学术机构的踪影的，最大的用途是给你将来申请大学做个参考，如果你非常自信的话。Top 10期刊，中国期刊就更加没戏，能被SCI收录就很自豪了。结果高影响力论文的数量最多Top 10的科学家里居然有一个中国人的名字----Yi Zhang！排在第7位。2002-2006年期间分子生物学和遗传学领域最具影响力的1300篇高影响力论文有Yi Zhang的11篇高影响力论文。

    张毅是谁？这么牛！生物通编辑检索了一篇，发现北卡罗莱纳大学医学院生物化学与生物物理学系教授，霍华德·休斯医学研究院(HHMI)研究员的张毅教授应该就是这个令人无比敬仰的牛人。看看他的实验室主页中的发表文章，满眼的CNS（Cell，Nature，Science）文章耀得眼都花了。北卡莱罗纳大学Howard Hughes Medical Institute此次名列学术机构前10名的首位。不完全统计，张毅教授实验室2001年到2006年间发表3篇Cell，4篇Science，3篇Nature和1篇Nature 子刊。2007年还有2篇Cell，1篇Nature和Nature子刊3篇。不单高产，质量也非常之高。张毅教授去年曾经回国访问，分别在中科院生物物理研究所和上海生科院做了报告。回头看看国内的SCI之争，为啥我们文章发SCI收录期刊就这么难呢？咱们发篇Science就那么了不得，人家怎么就一篇接一篇的发Cell啊？水平问题。我们是否应该更关注如何提高研究水平？

    另外2月的科学观察评选的快速突破论文中，重庆大学的邓林红教授2006年发表在Nature的论文也入选Fast Breaking Papers，这也是科学观察对最近取得显著进展或具有特别影响的科研领域进行引用分析和评论，筛选出覆盖面很广的22个科学领域里引用率最高的论文，构成了各领域每年前1%的顶尖论文，每两个月更新一次入选论文。入选“快速突破论文”不仅引用率高，而且在每两个月更新期间的引用增长率最高，因此代表了正在日益得到科学界关注的最新的科学贡献，从而被冠以“快速突破论文”。详细介绍请看生物通报道邓林红论文当选《科学观察》快速突破论文。（生物通记者）
 

生物通有关张毅和邓林红的文章

• 华人科学家《细胞》文章解析癌基因激活关键蛋白

• 张毅教授《自然》子刊文章解析组蛋白修饰

• 张毅等人顶级杂志上揭示新遗传和化学分析方法

• 张毅又一重要癌症研究文章

• 张毅《自然》文章

• HHMI：张毅发现一类进行基因调控新蛋白   • 邓林红论文当选《科学观察》快速突破论文 • 重庆大学邓林红等在《Nature》发表关于细胞力学的论文

Zhang Yi, PhD
Professor

Dr. Yi Zhang is currently an investigator at the Howard Hughes Medical Institute and a professor in the Department of Biochemistry and Biophysics at The University of North Carolina at Chapel Hill. He obtained his Ph.D. from The Institute of Molecular Biophysics at The Florida State University where he studied the molecular mechanism of the "hammerhead" ribozyme in the laboratory of Dr. Lloyd Epstein.

Research Interests

Epigenetic Modifications and Their Role in Cellular Memory and Cancer

Epigenetic modifications, particularly DNA methylation and covalent histone modifications, play an important role in regulating chromatin dynamics and therefore have a significant impact on gene expression. Our lab is interested in how epigenetic-mediated dynamic changes in chromatin structure affect gene expression, cell lineage commitment and cancer development. Our long-term goal is to apply this basic research to studies of human diseases.

Studies in our lab focus on four different areas. One is the relationship between ATP-dependent nucleosome remodeling and histone deacetylation. This area of study focuses on the nucleosome remodeling and deacetylase complex NuRD which we have recently demonstrated also plays an important role in methylated DNA silencing. We use a combination of biochemical and mouse genetic approaches to understand its biological function and the underlying mechanism through identification of its target genes by a genome wide localization approach. Our recent studies have linked its function to the autoimmune disease Lupus.

The second area of study involves the identification and characterization of novel covalent histone modifiers. Thus far, we have identified several novel histone methyltransferases including PRMT1, SET7, SET8, ESET, EZH2, and hDOT1. Our preliminary studies suggest that several of the enzymes are potentially involved in cancer. For example, the EZH2 protein has been linked to several types of solid cancers and hDOT1 has been linked to leukema. We have also recently identified several histone demethylases by using a novel biochemical assay. We are currently working to characterize these proteins.

Our third area of focus involves the role of various epigenetic modifications in cell lineage commitment, maintenance, and stem cell biology. Our goal is to identify a cell lineage or stem cell specific histone modification patterns and then to address the role of these histone modifications in the cell lineage commitment and maintenance process. Our fourth area of research involves identification and characterization of small chemical compounds that can modulate the enzymatic activities that have been mentioned above. By performing high-throughput screening followed by in vitro and in vivo verification, we hope to identify leading compounds for drug development. For more information, please visit our web page at http://www.med.unc.edu/~zhangyi/lab.htm.

Representative Publications

Wang H-B, Huang Z-Q, Li X, Feng Q, Erdjument-Bromage H, Strahl BD, Briggs S, Allis DC, Wong J, Tempst P, Zhang Y: Methylation of histone H4 at arginine 3 facilitates transcriptional activation by nuclear hormone receptor. Science 293: 853-857, 2001.  

Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y: Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298: 1039-1043, 2002.  

Min J, Feng Q, Li Z, Zhang Y, Xu R-M: Structure of the catalytic domain of human Dot1L, a non-SET domain nucleosomal histone methyltransferase. Cell 112: 711-723, 2003.  

Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, de la Cruz CC, Otte A, Panning B, Zhang Y: Role of histone H3 lysine 27 methylation in X-inactivation. Science 300: 131-135, 2003.  

Wang H-B, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones RS and Zhang Y: Role of H2A ubiquitination in Polycomb silencing. Nature 431: 873-878, 2004.  

Okada, Y., Feng, Q., Lin, Y., Jiang, Q., Li, Y., Coffeild, V.M., Su, L., Xu, G., & Zhang, Y. (2005). hDOT1L Links Histone Methylation to Leukemogenesis. Cell 121, 167-178.  

Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M.E., Borchers, C.H., Tempst, P., & Zhang,Y. (2006). Histone demethylation be a family of JmjC domain-containing proteins. Nature 439:811-816.

Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J., & Zhang, Y. (2006). JHDM2A, a JmjC-Containing H3K9 Demethylase, Facilitates Transcription Activation by Androgen Receptor. Cell 125(3):483-95.

Klose, R.J., Yamane, K., Bae, Y., Zhang D., Erdjument-Bromage, H., Tempst, P., Wong, J., & Zhang, Y. (2006) The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature 442:312-316.  

Okada, Y., Jiang, Q., Lemieux, M., Jeannotte, L., Su, L. & Zhang, Y. (2006) Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L. Nat. Cell Bio. 8(9):1017-1024.  

Huang, Y., Fang, J., Bedford, M.T., Zhang, Y., & Xu, R-M. (2006). Recognition of Histone H3 Lysine -4 Methylation by the Double Tudor Domain of JMJD2A. Science 312(5774):748-51.

Liang, G., Klose, R.J., Gardner, K.E., & Zhang, Y. 2007. Yeast Jhd2p is a histone H3 Lys4 trimethyl demethylase. Nat. Struct. & Mol. Bio. 14:243-245.

Klose, R.J., Yan, Q., Tothova, Z., Yamane, K., Erdjument-Bromage, H., Tempst, P., Gilliland, D.G., Zhang, Y., & Kaelin, W.G. 2007. The Retinoblastoma Binding Protein RBP2 is an H3K4 demethylase. Cell. 128:889-900.

Lee, N., Zhang, J., Klose, R.J., Erdjument-Bromage, H., Tempst, P., Jones, R.S., & Zhang, Y. 2007. The trithorax-group protein Lid is a histone H3 trimethyl-Lys4 demethylase. Nat. Struct. & Mol. Bio. 14(4): 341-3.

Klose, R.J., & Zhang, Y. 2007. Regulation of histone methylation by demethylimination and demethylation. Nat. Rev. M.C.B. 8(4): 307-18.

Yamane, K., Tateishi, K., Klose, R.J., Fang, J., Fabrizio, L.A., Erdjument-Bromage, H., Taylor-Papadimitriou, J., Tempst, P., & Zhang, Y. 2007. PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol.Cell. 25(6): 801-12.

Klose, R.J., Gardner, K.E., Liang, G., Erdjument-Bromage, H., Tempst, P., & Zhang, Y. (2007) Demethylation of histone H3K36 and H3K9 by Rph1: a zestige of an H3K9 methylation system in Saccharomyces cerevisiae? MCB. 27:3951-3961.

Fang, J., Hogan, G.J., Liang, G., Lieb, J.D., & Zhang, Y. (2007) The Saccharomyces cerevisiae histone demethylase Jhd1 fine-tunes the distribution of H3K36me2. MCB. 27:5055-65.

Okada, Y., Scott, G., Ray, M.K., Mishina, Y., & Zhang, Y. (2007) Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis. Nature. 450:119-123.

Klose, R.J. & Zhang Y. (2007) Histone H3 Arg2 methylation provides alternative directions for COMPASS. Nat.Struct.Mol.Biol. 14(11):1058-60.

Allis, C.D., Berger, S.L., Cote, J., Dent, S., Jenuwien, T., Kouzarides, T., Pillus, L., Reinberg, D., Shi, Y., Shiekhattar, R., Shilatifard, A., Workman, J., Zhang, Y. (2007) New nomenclature for chromatin modifying enzymes. Cell. 131(4):633-6.