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專任教師

陳美如 教授

聯絡電話:02-2312-3456 轉 88291 or 88933

E-mail: mrc@ntu.edu.tw

個人資料

專長:

1.參與DNA複製與修補的病毒及細胞因子之交互作用
2.病毒蛋白質激酶對於細胞週期調控及訊息傳遞路徑
3.病毒感染時細胞內胞器的變化與細胞內傳輸機制之相關性
4.EB病毒引起人類癌症之分子機轉

學歷:

Ph.D. 1986-1991, Graduate Institute of Microbiology/National Taiwan, University, Taipei/Taiwan
Master 1984-1986, Grduate Institute of Microbiology/ National Taiwan, University, Taipei/Taiwan
Bachelor 1980-1984, Department of Medical Technology, Taipei Medical University, Taiwan

經歷:

1. 1991-1994, Post Doctoral fellow, Oncology Center, Johns Hopkins School of Medicine
2. 1994-1995, Instructor, Graduate Institute and Department of Microbiology, National Taiwan University
3. 1995-2008, Associate Professor, Graduate Institute and Department of Microbiology, National Taiwan University
4. 2008, Professor, Graduate Institute and Department of Microbiology, National Taiwan University

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目前進行研究

      

-         The interplay between Epstein-Barr virus (EBV) and cellular machineries.

My laboratory is interested in studying how different viral factors of EBV manipulate cellular machinery to facilitate virus replication. EBV infects most of population worldwide; however it is also linked to several malignant diseases. The ultimate goal is to develop future management protocols for EBV associated diseases. EBV is a gamma-herpesvirus with a 172-kb DNA genome, which replicates and encapsidated within host nucleus. Two different aspects of research are focused in our current study.

I. Viral DNA replication machinery, DNA repair and transcriptional control

   EBV DNA replication machinery resembles a miniature of mammalian DNA replication process, which involved viral and cellular factors. In addition to the basic viral DNA polymerase/helicase/primase complex, several accessory factors participate in the viral DNA replication process. The viral encoded BKRF3 uracil DNA glycosylase is also recruited into the replication compartment and play multiple roles to facilitate viral DNA replication. The viral DNA polymerase processivity factor BMRF1 also can function as a transcriptional co-activator to regulate different viral promoters. We are interested in the role of viral encoded protein kinase BGLF4 in regulating different function of viral proteins in the replication complex.

 

II. The mechanism of EBV nuclear egress

    After DNA replication, EBV nucleocapsids need to be transported from nucleus into cytoplasm for subsequent tegumentation before virion maturation. Several viral proteins are involved in modifying the nuclear envelope structure. The viral BGLF4 protein kinase can induce chromosome condensation and partial disassembly of nuclear lamina. Our recent study also showed the cellular endosomal sorting complex required for transport (ESCRT) machinery is required for the nuclear egress of EBV. The integrity of nuclear envelope is functionally associated with cell migration, cell division, gene expression and intracellular signaling; even single mutation on nuclear lamin genes may cause severe diseases. Therefore the study of virus mediated modification of nuclear envelope structure may also reveal novel regulatory pathways of nuclear morphology.

III. The control of nuclear-cytoplasmic trafficking

  EBV genome is delivered into nucleus and maintained as circular form during its latency. Many virus encoded proteins function in the nucleus were found lacking classical nuclear localization signals. Our recent studies suggesting viral encoded protein kinase BGLF4 may play important regulatory roles for nucleo-cytoplamic trafficking control.

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研究室成員

碩士班學生: 謝宜君、廖晏慈、徐維逸、王姿云、徐憶婷、黃暐涵
碩士級助理;張棹杬
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研究成果

SELECTED PUBLICATION
1.Lee CP, Liu GT, Kung HN, Liu PT, Liao YT, Chow LP, Chang LS, Chang YH, Chang CW, Shu WC, Angers A, Farina A, Lin SF, Tsai CH, Bouamr F and Chen MR*. The Ubiquitin Ligase Itch and Ubiquitination Regulate BFRF1-mediated Nuclear Envelope Modification for EBV Maturation. (J Virol. 2016, 90:8994-9007. doi: 10.1128/JVI.01235-16).
2.Chang CW, Lee CP, Su MZ, Tsai CH and Chen MR*. BGLF4 Kinase Modulates the Structure and Transport Preference of the Nuclear Pore Complex to Facilitate Nuclear Import of Epstein-Barr Virus Lytic Proteins. J. Virol. 2015 89:1703- 1718.
3.Su MT, Liu IH, Wu CW, Chang SM, Tsai CH, Yang PW, Chuang YC, Chung-Pei Lee CP and Chen MR*. Uracil DNA glycosylase BKRF3 contributes to Epstein-Barr virus DNA replication through physical interactions with proteins in viral DNA replication complex. J. Virol. 2014, 88(16):8883.
4.Wang JT, Chang LS, Chen CJ, Doong SL, Chang CW, Chen MR*. Glycogen Synthase Kinase 3 Negatively Regulates Interferon Regulatory Factor 3 Transactivation through Phosphorylation at Its Linker Region. Innate Immunity 2014, 20: 78–87.
5.Chang LS, Wang JT, Doong SL, Lee CP, Chang CW, Tsai CH, Yeh SW, Hsieh CY, Chen MR*. Epstein-Barr Virus BGLF4 Kinase Down-regulates NF-κB Transactivation through Phosphorylation of Coactivator UXT. J. Virol. 2012, 86(22):12176.
6.Lee CP, Liu PT, Kung HN, Su MT, Chua HH, Chang YH, Chang CW, Tsai CH, Liu FT, Chen MR*. The ESCRT Machinery Is Recruited by the Viral BFRF1Protein to the Nucleus-Associated Membrane for the Maturation of Epstein-Barr Virus. PLOS Pathogens 2012, 8 (9): e1002904.
7.Chang YH, Lee CP, Su MT, Wang JT, Chen JY, Lin SF, Tsai CH, Hsieh MJ, Takada K, Chen MR*. Epstein-Barr Virus BGLF4 Kinase Retards Cellular S-Phase Progression and Induces Chromosomal Abnormality. PLoS ONE 2012, 7 (6): e39217.
8.Chang CW, Lee CP, Huang YH, Yang PW, Wang JT and Chen MR*. Epstein-Barr Virus Protein Kinase BGLF4 Targets the Nucleus through Interaction with Nucleoporins. J. Virol. 2012, 86(15):8072.
9.Epstein-Barr virus, the immune system, and associated diseases. Chen MR*. Front Microbiol. 2011;2:5. (Perspective)
10.Wang JT, Chuang YC, Chen KL, Lu CC, Doong SL, Cheng HH, Chen YL, Liu TY, Chang Y, Han CH, Yeh SW, Chen MR*. Characterization of Epstein-Barr virus BGLF4 kinase expression control at the transcriptional and translational levels. J Gen Virol. 2010 Sep;91(Pt 9):2186-96.
11.Chen PW, Lin SJ, Tsai SC, Lin JH, Chen MR, Wang JT, Lee CP, Tsai CH. Regulation of microtubule dynamics through phosphorylation on stathmin by Epstein-Barr virus kinase BGLF4. J Biol Chem. 2010 Mar 26;285(13):10053-63.
12.Lee CP and Chen MR*. Escape of herpesviruses from the nucleus. Reviews in Medical Virology. Review in Medical Virology 2010. 20(4):214-30.
13.Wang, JT, Doong SL, Teng SC, Lee CP, Tsai CH and Chen MR*. Epstein-Barr Virus BGLF4 Kinase Suppresses Interferon Regulatory Factor 3 Signaling. J Virol 2009;83:1856-1869.
14.Lee CP, Huang YH, Lin SF, Chang Y, Chang YH, Takada K and Chen MR*. Epstein-Barr Virus BGLF4 Kinase Induces Disassembly of the Nuclear Lamina to Facilitate Virion Production. J Virol 2008;82:11913-11926.
15.Yang PW, Chang SS, Tsai CH, Chao YH, and Chen MR*. The effect of phosphorylation on the transactivation activity of Epstein-Barr Virus BMRF1, a major target of the viral BGLF4 kinase. J Gen Virol 2008;89:884-895.
16.Lu CC, ChenYC, Wang JT, Yang PW, and Chen MR*. Xeroderma pigmentosum C (XPC) is involved in Epstein-Barr virus DNA replication. J Gen Virol 2007;88:3234-3243.
17.Lee CP, Chen JY, Wang TJ, Kimura K, Takemoto A, Lu CC, and Chen MR*. Epstein-Barr virus BGLF4 kinase induces premature chromosome condensation through activation of condensin and topoisomerase II. J Virol 2007;81:5166-5180.
18.Lu CC, Huang HT, Wang JT, Slupphaug G, Li TK, Wu MC, Chen YC, Lee CP, and Chen MR*. Characterization of the uracil-DNA glycosylase activity of Epstein-Barr virus BKRF3 and its role in lytic viral DNA replication. J Virol 2007;81:1195-1208.
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