科研方向
一、組蛋白修飾以及調(diào)控核小體組裝的功能研究
?表觀遺傳學(xué)是目前生物醫(yī)學(xué)研究最有前景的熱點(diǎn)方向之一，它是指在不改變DNA序列的前提下而調(diào)控基因的表達(dá)。真核細(xì)胞的雙鏈DNA與組蛋白亞基(H2A, H2B, H3和H4)緊密結(jié)合，形成DNA纏繞的組蛋白八聚體復(fù)合物即核小體，核小體經(jīng)過進(jìn)一步壓縮而成染色質(zhì)。盡管組蛋白-DNA的結(jié)合非常牢固，但細(xì)胞內(nèi)的核小體處于一種動(dòng)態(tài)的穩(wěn)定狀態(tài)。在DNA復(fù)制、轉(zhuǎn)錄及修復(fù)過程中，核小體進(jìn)行連續(xù)不斷的解聚和重新組裝，而核小體解聚和重新組裝是被嚴(yán)密調(diào)控的；有多種蛋白質(zhì)參與這一過程。其中，組蛋白修飾酶和組蛋白伴侶蛋白是作為核心成員參與這一重要的細(xì)胞生理活動(dòng)。我們主要研究組蛋白翻譯后修飾，以及組蛋白修飾如何調(diào)控核小體的解聚和重新組裝的分子機(jī)制，該研究將有助于人們更為深入地認(rèn)識DNA復(fù)制這一最為基本的生命活動(dòng)。
二、篩選腫瘤的表觀遺傳性治療藥物
以前，腫瘤被認(rèn)為是由持續(xù)的基因組不穩(wěn)定性包括染色體異常和癌基因／抑癌基因突變而引起的一種疾��；如今，越來越多的證據(jù)顯示腫瘤是由表觀遺傳學(xué)的改變而促發(fā)的疾病。腫瘤表觀遺傳學(xué)研究已經(jīng)成為腫瘤研究的主流方向。表觀遺傳學(xué)的信息是儲存在染色質(zhì)中，而染色質(zhì)的基本組成單元為核小體—即長146對堿基的DNA纏繞在組蛋白八聚體的結(jié)構(gòu)。細(xì)胞眾多功能的調(diào)節(jié)正是通過核小體和染色質(zhì)結(jié)構(gòu)的修飾而完成，表觀遺傳學(xué)修飾包括組蛋白的翻譯后修飾和DNA甲基化與去甲基化，它們是調(diào)節(jié)基因表達(dá)和維持基因組穩(wěn)定性最為關(guān)鍵的方式。因此闡明表觀遺傳學(xué)修飾和基因組穩(wěn)定性之間聯(lián)系的分子機(jī)理對于我們了解腫瘤的形成、發(fā)展以及尋找治療腫瘤的靶點(diǎn)分子意義重大。
三、表觀遺傳學(xué)調(diào)控干細(xì)胞命運(yùn)
組蛋白修飾參與精密調(diào)控DNA復(fù)制、DNA修復(fù)和基因轉(zhuǎn)錄等過程，其中研究最多和較為透徹的是組蛋白甲基化、乙�；土姿峄�，少有研究涉及組蛋白H3泛素化及其調(diào)控基因轉(zhuǎn)錄等。探索組蛋白H3泛素化修飾對染色質(zhì)結(jié)構(gòu)的影響，以及組蛋白H3修飾間的關(guān)聯(lián)動(dòng)態(tài)變化規(guī)律、闡明組蛋白H3修飾間關(guān)聯(lián)協(xié)同調(diào)節(jié)基因轉(zhuǎn)錄和表達(dá)，進(jìn)而調(diào)控干細(xì)胞自我更新、干性維持和分化的機(jī)制。
學(xué)術(shù)任職
擔(dān)任《DNA and Cell Biology》和《Frontier in Genetics》等國際學(xué)術(shù)期刊特邀審稿人
榮譽(yù)記錄
1. 愛德華·肯德爾杰出研究獎(jiǎng) (Edward C.Kendall Award for Meritorious Research)
2. 愛德華·肯德爾獎(jiǎng)學(xué)金 (Edward C.Kendall Award Fellowship)
3. 美國心臟學(xué)會(huì)獎(jiǎng)學(xué)金 (American Heart Association Fellowship)
4. 日本政府獎(jiǎng)學(xué)金 (Japanese Government Scholarship)
5. 四川省衛(wèi)生計(jì)生領(lǐng)軍人才（2015）
著述成果
【代表性論著】
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。