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  韩俊宏

【简介】
 
   韩俊宏,研究员,博士生导师,教育部长江学者奖励计划特聘教授2005年在日本东京工业大学(Tokyo Institute of Technology)获得博士学位。2006年至2008年,在美国梅奥医学中心(Mayo Clinic)接受博士后训练2009-2014年先后任职资深助理研究员(Senior Research Fellow),研究助理(Research Associate)和助理教授(Assistant Professor至今,已在包括 Science, Cell, Nature, Genes & Development, Molecular Cell, Nature Structure & Molecular Biology, Journal Biological Chemistry等国际权威学术期刊上发表多篇研究论文。研究工作被包括 Nature Reviews Molecular Cell Biology, Faculty 1000等著名期刊作重点评述。文章总影响因子216.3,总引用次数为1482次。此外,1项美国专利。
 
【研究方向】
 
一、组蛋白修饰以及调控核小体组装的功能研究
 
 表观遗传学是目前生物医学研究最有前景的热点方向之一它是指在不改变DNA序列的前提下而调控基因的表达。真核细胞的双链DNA与组蛋白亚基(H2A, H2B, H3H4)紧密结合,形成DNA缠绕的组蛋白八聚体复合物即核小体,核小体经过进一步压缩而成染色质。尽管组蛋白-DNA结合非常牢固,但细胞内的核小体处于一种动态的稳定状态。在DNA制、转录及修复过程中,核小体进行连续不断的解聚和重新组装,而核小体解聚和重新组装是被严密调控的;有多种蛋白质参与这一过程。其中,组蛋白修饰酶和组蛋白伴侣蛋白是作为核心成员参与这一重要的细胞生理活动。我们主要研究组蛋白翻译后修饰,以及组蛋白修饰如何调控核小体的解聚和重新组装的分子机制,该研究将有助于人们更为深入地认识DNA复制这一最为基本的生命活动。
 
二、筛选肿瘤的表观遗传性治疗药物
 
       以前肿瘤被认为是由持续的基因组不稳定性包括染色体异常和癌基因抑癌基因突变而引起的一种疾病如今越来越多的证据显示肿瘤是由表观遗传学的改变而促发的疾病。肿瘤表观遗传学研究已经成为肿瘤研究的主流方向。表观遗传学的信息是储存在染色质中而染色质的基本组成单元为核小体即长146对碱基的DNA缠绕在组蛋白八聚体的结构。细胞众多功能的调节正是通过核小体和染色质结构的修饰而完成表观遗传学修饰包括组蛋白的翻译后修饰和DNA甲基化与去甲基化,它们是调节基因表达和维持基因组稳定性最为关键的方式。因此阐明表观遗传学修饰和基因组稳定性之间联系的分子机理对于我们了解肿瘤的形成、发展以及寻找治疗肿瘤的靶点分子意义重大。
 
   三、表观遗传学调控干细胞命运
 
    蛋白修参与精密DNA复制、DNA修复和基因转录程,其中研究最多和较为的是蛋白甲基化、乙化和磷酸化,少有研究涉及蛋白H3泛素化及其控基因转录等。探索组蛋白H3泛素化修饰对染色质结构的影响,以及组蛋白H3修饰间的关联动态变化规律、阐明组蛋白H3修饰间关联协同调节基因转录和表达,进而调控干细胞自我更新、干性维持和分化的机制。
 
学术任职
 
   担任《DNA and Cell Biology》和《Frontier in Genetics等国际学术期刊特邀审稿人
 
获奖
 
1.     爱德华·肯德尔杰出研究奖 (Edward C.Kendall Award for Meritorious Research)
2.     爱德华·肯德尔奖学金 (Edward C.Kendall Award Fellowship)
3.     美国心脏学会奖学金 (American Heart Association Fellowship)
4.     日本政府奖学金 (Japanese Government Scholarship)
5.     教育部长江学者奖励计划特聘教授(2014
6.     四川省卫生计生领军人才(2015
 
代表性论著
1.       Junhong Han, Yuichi Tsukada, Eiji Hara, Naomi Kitamura, Toshiaki Tanaka. Hepatocyte Growth Factor Induces Redistribution of p21Cip1 and p27Kip1 Through Erk-dependent p16INK4a Up-regulation, Leading to Cell Cycle Arrest at G1 in HepG2 Hepatoma Cells. Journal of Biological Chemistry. 2005, 280:31548-31556.
2.       Junhong Han, Hui Zhou, Bruce Horazdovsky, Kanling Zhang, Rui-Ming Xu, Zhiguo Zhang.Rtt109 Acetylates Histone H3 Lysine 56 and Functions in DNA Replication. Science 2007,315:653-655. (Highlighted by Nature Reviews Molecular Cell Biology and by Faculty of 1000)
3.       Sean R. Collins, Kyle M. Miller, Nancy L. Maas, Assen Roguev, Jeffrey Fillingham, Clement S.Chu, Maya Schuldiner, Marinella Gebbia, Judith Recht, Michael Shales, Huiming Ding, HongXu, Junhong Han, Kristin Ingvarsdottir, Benjamin Cheng, Brenda Andrews, Charles Boone,Shelley L. Berger, Phil Hieter, Zhiguo Zhang, Grant W.Brown, C. James Ingles, Andrew Emili,C. David Allis, David P. Toczyski, Jonathan S. Weissman , Jack F. Greenblatt, Nevan J.Krogan. Functional Dissection of Protein Complexes Involved in Yeast Chromosome BiologyUsing a Genetic Interaction Map. Nature 2007, 446: 806-810. (Highlighted by Faculty of 1000)
4.       Junhong Han, Qing Li, Laura McCullough, Tim Formosa, Zhiguo Zhang. Ubiquitylation of FACT by the Cullin-E3 Ligase Rtt101 Connects FACT to DNA Replication. Genes & Development. 2010, July 15, 24(14):1485-1490. PMCID: PMC2904938.(Highlighted by Faculty of 1000)
5.       Junhong Han, Hui Zhou, Z. Li, Rui-Ming Xu, Zhiguo Zhang. H3-K56 Acetylation Catalyzed by Rtt109 and Regulated by Asf1 is Required for Replisome Integrity. Journal of Biological Chemistry. 2007, 282:28587-28596.
6.       Junhong Han, Hui Zhou, Zhizhong Li, Rui-Ming Xu, Zhiguo Zhang. The Rtt109-Vps75 Histone Acetyltransferase Complex Acetylates Non-nucleosomal Histone H3. Journal of Biological Chemistry. 2007, 282:14158-14164.
7.       Chuanhe Yu*, Haiyun Gan*, Junhong Han, Zhixiong Zhou, Shaodong Jia, Andrei Chabes, Gianrico Farrugia, Tamas Ordog, Zhiguo Zhang. Strand-Specific Analysis Shows Protein Binding at Replication Forks and PCNA Unloading from Lagging Strands when Forks Stall. Molecular Cell. 2014 Nov.20, 54:551-563 (*Equal Contribution).
8.       Karina B. Falbo*, Contance Alabert*, Yuki-Mori Katou*, Su Wu, Junhong Han, Tammy Wehr,Jing Xiao, Xiangwei He, Zhiguo Zhang, Yang Shi, Katsuhiko Shirahige, Philippe Pasero,Xuetong Sheng. Involvement of a Chromatin Remodeling Complex in DNA Damage Tolerance in DNA Replication. Nature Structural and Molecular Biology. 2009, 16:1167-1172 (*Equal Contribution).
9.       Rebecca J. Burgess, Hui Zhou, Junhong Han, Zhiguo Zhang. Gcn5 Promotes Replication Coupled Nucleosome Assembly. Molecular Cell. 2010, Feb.26, 37(4):469-480. PMCID: PMC2954627.
10.   Theodore J. Kottom, Junhong Han, Zhiguo Zhang, Andrew H. Limper. Pneumocystis cariniiexpress an Active Rtt109 Histone Acetyltransferase. American Journal of Respiratory Cell and Molecular Biology. 2011,44:768-776. PMCID: PMC3135839.
11.    Hui Zhang, Junhong Han, Bin Kan and Zhiguo Zhang. Human HAT1 Preferentially Acetylates H3.1-H4 over H3.3-H4 Tetramers and Regulates Nucleosome Assembly of H3.1-H4. Journal of Biological Chemistry. 2012, 287, 6573-6581.
12.   Rebecca J. Burgess, Junhong Han, Zhiguo Zhang. The Ddc1/Mec3/Rad17 Sliding Clamp Regulates Histone-histone Chaperone Interactions and DNA Replicaiton-Coupled Nucleosome Assembly in Budding Yeast. Journal of Biological Chemistry. 2014 Feb.25, 289:10518-10529.
13.   Rebecca J. Burgess, Hui Zhou, Junhong Han, Zhiguo Zhang. The SCFDia2 Ubiquitin E3 Ligase Ubiquitylates Sir4 and Functions in Transcriptional Silencing. PLoS Genetics. 2012 Jul; 8(7): e1002846.
14.   Jayme L. Dahlin, Rondedrick Sinville, Jonathan Solberg, Hui Zhou, Junhong Han, Subhashree Francis, Jessica M. Strasser, Kristen John, Derek J. Hook, Michael A. Walters, Zhiguo Zhang. A Cell-Free Fluorometric High-throughput Screen for Inhibitors of Rtt109 -catalyzed Histone Acetylation. PLoS One. 2013 Nov.18; 8(11):e78877. Doi:10.1371/journal.pone.0078877
15.   Junhong Han, Hui Zhang, Honglian Zhang, Zhiquan Wang, Hui Zhou and Zhiguo Zhang. A Cul4 E3 Ubiquitin Ligase Regulates Histone Hand-off During Nucleosome Assembly. Cell. 2013. 155:817-829. (Highlighted by Faculty of 1000)
16.   Jayme L. Dahlin, Theodore Kottom, Junhong Han, Hui Zhou, Michael A. Walters, Zhiguo Zhang and Andrew H. Limper. Pneumocystis Jirovecil PjRtt109: A Novel Drug Target for Pneumocystis Pneumonia in Immunosuprressed Humans. Antimicrobial Agents and Chemotherapy. 2014 July, 58:3650-3659.
17.   Kuo Zhang, Yuan Gao, Jingjing Li, Rebecca Burgess, Junhong Han, Huanhuan Liang, Zhiguo Zhang, Yingfang Liu. A DNA Binding Winged Helix Domain in CAF-1 Functions with PCNA to Stabilize CAF-1 at Replication Forks. Nucleic Acids Research. 2016, doi:10.1093/nar/gkw106
 
系方式】
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**欢迎对生物医学研究有浓厚兴趣的学生报考博、硕士研究生;也热烈欢迎应届博士毕业生垂询博士后职位。
 
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