NTUBST2019

• 長庚大學 基礎醫學研究所 博士(1997/09 ~ 2001/01)
• 臺灣大學 植物學研究所 碩士(1991/09 ~ 1993/06)
• 臺灣大學 植物學系 學士(1987/09 ~ 1991/06)

本研究室長期以來利用EBV致力於宿主調控病毒蛋白質後轉譯修飾之機制、及探討病毒如何利用宿主調控病毒基因的表現。EBV為人類疱疹病毒科的致癌病毒，與B淋巴癌胃癌及鼻咽癌等高度相關，最新研究更指出EBV是引發多發性硬化症及紅斑性狼瘡的主因，讓EBV與自體免疫疾病的關聯性又更加密切，而EBV的再活化可能參與此致病機制。Rta是病毒再活化進入溶裂期最早表現的病毒轉錄因子之一，長期以來一直被認為只有在溶裂期才會表現。過去本研究室對Rta的功能有長期且深入的研究，我們首度發現Rta的SUMO修飾及泛素化修飾，進而影響病毒的溶裂期進展。我們也找到許多宿主的蛋白質，包含MCAF1, RanBPM, ATF2, TAF4等都會參與Rta所調控的病毒或宿主的基因轉錄。另外我們也發現Rta在B細胞的潛伏期就會表現，這在EBV的研究上是很重要的發現，Rta會與MCRS2結合聚集在核仁，以避免溶裂期基因被活化。同時也發現Rta會促進細胞的轉譯，顯示其在潛伏期可能具有重要的功能。另外我們也首度證實Rta存在於病毒顆粒內，與殼體蛋白質結合，是一個tegument protein，對於殼體蛋白質的穩定性很重要。而TRIM5α，它是一種反轉錄病毒限制因子，同時也具有ubiquitin E3 ligase的活性，會抑制HIV的感染。我們最先利用蛋白質體分析發現TRIM5α會與Rta結合，由於TRIM5α是一種泛素E3接合酶，會促進Rta的泛素化修飾進而抑制病毒的增殖。之後也證實TRIM5α會結合病毒的殼體蛋白質BORF1，促進其泛素化使其以TRIMosome的方式進行精準自噬，因此抑制EBV的溶裂期進展，此發現顯示TRIM5α也會參與DNA病毒的調控。最近我們發現細胞的去泛素酶USP11可以移除Rta與Zta的泛素鏈，因此促進病毒顆粒的產生。另外我們也發現Rta會調節先天免疫反應的cGAS-STING路徑，其機制可能是藉由Rta誘發STING的自噬降解所造成的。我們將深入探究Rta如何藉由去泛素酶調節先天免疫反應路徑中的重要蛋白質，進而拮抗宿主的免疫反應，這對EBV的致病機制是很重要的。

• 臺灣大學 生化科技學系 教授(2015/08 ~ now)
• 臺灣大學 生化科技學系 副教授(2010/08 ~ 2015/07)
• 臺灣大學 生化科技學系 助理教授(2006/08 ~ 2010/07)
• 高雄醫學大學 生物醫學暨環境生物學系 助理教授(2003/08 ~ 2006/07)
• 高雄醫學大學 生物系 講師(1994/10 ~ 2003/07)

• 臺大教學傑出獎（2013, 2021）
• 臺大教學優良獎（2009, 2010, 2011, 2012, 2020）
• 長庚大學 第七屆傑出校友(2009)
• 高雄醫學大學生物系 傑出研究獎(2005)
• 高雄醫學院生物系 績優導師(1994)

1. Chen CY, Chen PC, Lu YS, Lin XR, Yang YC, Lee YK, Cheng ZY, Chang SY, Chiu YF, Chang LK*. Impact of deubiquitination of Epstein-Barr virus Rta and Zta on lytic development. Microbiol Spectr. 2026 Jul 7;14(7):e0415825. (*Correspondence)
2. Hsi HY, Wang SW, Hsiao G, Chang LK, Cheng YC, Huang SJ, Lu YS, Lee TH. Chemical constituents from a marine medicinal brown alga-derived Xylaria acuta SC1019. J Food Drug Anal. 2024 Jun 15;32(2):155-167.
3. Li YJ, Chen CY, Kuo YS, Huang YW, Kuo RL, Chang LK, Yang JH, Lai CH, Shih SR, Chiu YF. OTUB1 contributes to the stability and function of Influenza A virus NS2. PLoS Pathog. 2024 May 30;20(5):e1012279.
4. Lin LT, Lu YS, Huang HH, Chen H, Hsu SW, Chang LK*. Regulation of Epstein-Barr virus minor capsid protein BORF1 by TRIM5α. Int J Mol Sci. 2022 Dec 5;23(23):15340 (*Correspondence)
5. Chang CH, Lee YC, Hsiao G, Chang LK, Chi WC, Cheng YC, Huang SJ, Wang TC, Lu YS, Lee TH. Anti-Epstein–Barr viral agents from the medicinal herb-derived fungus Alternaria alstroemeriae Km2286. J Nat Prod. 2022 Nov 25;85 (11), 2667-2674.
6. Hwang SP, Huang LC, Wang WH, Lin MH, Kuo CW, Huang HH, Chang LK*. Expression of Rta in B Lymphocytes during Epstein-Barr Virus Latency. J Mol Biol. 2020 Sep 4;432(19):5227-5243. (*Correspondence)
7. Huang HH, Wang WH, Feng TH, Chang LK* (2020) Rta is an Epstein-Barr virus tegument protein that improves the stability of capsid protein BORF1. Biochem Biophys Res Commun. 2020 Mar 12;523(3):773-779. (*Correspondence)
8. Tsai YC, Hohmann J, El-Shazly M, Chang LK, Dankó B, Kúsz N, Hsieh CT, Hunyadi A, Chang FR (2020) Bioactive constituents of Lindernia crustacea and its anti-EBV effect via Rta expression inhibition in the viral lytic cycle. J Ethnopharmacol. 2020 Mar 25;250:112493.
9. Chang HY, Chen YC, Tuan WH, Hwang SP, Chang LK, Wu CJ, Chen CY, Lai PL. Biphasic bone graft prepared using a gel-foaming technique. Ceramics International. 2021 Mar 15;47(6):7805-7813.
10. Vágvölgyi M, Girst G, Kúsz N, Ötvös SB, Fülöp F, Hohmann J, Servais JY, Seguin-Devaux C, Chang FR, Chen MS, Chang LK, Hunyadi A (2019) Less cytotoxic Less cytotoxic protoflavones as antiviral agents: protoapigenone 1′-O-isopropyl ether shows improved selectivity against the Epstein-Barr virus lytic cycle. Int J Mol Sci. 20(24). Pii:E6269
11. Huang JY, Kang ST, Chen IT, Chang LK, Lin SS, Kou GH, Chu CY, Lo CF (2017) Shrimp miR-10a is co-opted by white spot syndrome virus to increase viral gene expression and viral replication. Front Immunol. 8:1084
12. Huang PH, Huang TY, Cai PS, Chang LK* (2017) Role of Litopenaeus vannamei Yin Yang 1 in the regulation of the white spot syndrome virus immediate-early gene ie1. J Virol. 91(6). pii: e02314-16. (*Correspondence)
13. Huang HH, Chen CS, Wang WH, Hsu SW, Tsai HH, Liu ST, Chang LK* (2017) TRIM5promotes ubiquitination of Rta from Epstein-Barr virus to attenuate lytic progression. Front Microbiol. 7:2129. (*Correspondence)
14. Chang TH, Wang SS, Chen LW, Shih YJ, Chang LK, Liu ST, Chang PJ. (2016) Regulation of the aboundance of Kaposi’s sarcoma-associated herpesvirus ORF50 protein by oncoprotein MDM2. PLoS Pathog. 12(10):e1005918.
15. Hung CC, Kuo CW, Wang WH, Chang TH, Chang PJ, Chang LK*, Liu ST*. (2015) Transcriptional activation of Epstein-Barr virus BRLF1 by USF1 and Rta. J Gen Virol. 96(9):2855-66. (*Correspondence)
16. Wang WH, Kuo CW, Chang LK, Hung CC, Chang TH, Liu ST. (2015) Assembly of Epstein-Barr virus capsid in promyelocytic leukemia nuclear bodies. J Virol. 89(17):8922-31.
17. Yang YC, Feng TH, Chen TY, Huang HH, Hung CC, Liu ST, Chang LK* (2015) RanBPM regulates Zta-mediated transcriptional activity in Epstein-Barr virus. J Gen Virol. 96(8):2336-48. (*Correspondence)
18. Liu WJ, Lo CF, Kou GH, Leu JH, Lai YJ, Chang LK, Chang YS (2015) The promoter of the white spot syndrome virus immediate-early gene WSSV108 is activated by the cellular KLF transcription factor. Dev Comp Immunol. 49(1):7-18.
19. Huang PH, Lu SC, Yang SH, Cai PS, Lo CF, Chang LK* (2014) Regulation of the immediate-early genes of white spot syndrome virus by Litopenaeus vannamei Kruppel-like factor (LvKLF). Dev Comp Immunol. 46:364-372 (*Correspondence)
20. Lin TY, Chu YY, Yang YC, Hsu SW, Liu ST, Chang LK* (2014) MCAF1 and Rta-activated BZLF1 transcription in Epstein Barr virus. PLoS One. 9(3):e90698. (*Correspondence)
21. Yang YC, Yoshikai Y, Hsu SW, Saitoh H*, Chang LK* (2013) Role RNF4 in the ubiquitination of Rta of Epstein-Barr virus. J. Biol. Chem. 288:12866-12879. (*Correspondence)
22. Yang YC and Chang LK* (2013) Role of TAF4 in transcriptional activation by Rta of Epstein-Barr virus. PLoS One. 8(1):e54075 (*Correspondence)
23. Chang LK*, Huang PH, Shen WT, Yang SH, Liu WJ, Lo CF* (2012) Role of Penaeus monodon Kruppel-like factor (PmKLF) in infection by white spot syndrome virus. Dev Comp Immunol. 36(1):121-129 (*Correspondence)
24. Wang WH, Chang LK, Liu ST (2011) Molecular interactions of Epstein-Barr virus capsid proteins. J Virol. 85(4):1615-24.
25. Chen CC, Yang YC, Wang WH, Chen CS, Chang LK* (2011) Enhancement of Zta-activated lytic transcription of Epstein-Barr virus by Ku80. J Gen Virol. 92:661-8. (*Correspondence)
26. Yiu CY, Chen SY, Chang LK, Chiu YF, Lin TP (2010) Inhibitory effects of resveratrol on the Epstein-Barr virus lytic cycle. Molecules. 15(10):7115-24.
27. Chou CH, Lieu AS, Wu CH, Chang LK, Loh JK, Lin RC, Chen WJ, Liao HD, Fu WS, Chang CS, Lin CC, Hsu CM, Chio CC, Howng SL, Hong YR (2010) Differential expression of hedgehog signaling components and Snail/E-cadherin in human brain tumors. Oncol Rep. 24(5):1225-1232.
28. Lieu AS, Cheng TS, Chou CH, Wu CH, Hsu CY, Huang CY, Chang LK, Loh JK, Chang CS, Hsu CM, Howng SL, Hong YR (2010) Functional characterization of AIBp, a novel Aurora-A binding protein in centrosome structure and spindle formation. Int J Oncol. 37(2):429-436.
29. Shin YC, Liu BY, Tsai JY, Wu JT, Chang LK, Chang SC (2010) Biochemical characterization of the small ubiquitin-like modifiers of Chlamydomonas reinhardtii. Planta. 232(3):649-662.
30. Chang LK, Chuang JY, Nakao M, Liu ST (2010) MCAF1 and synergistic activation of the transcription of Epstein-Barr virus lytic genes by Rta and Zta. Nucleic Acids Res. 38(14): 4687-4700.
31. Chang FR, Hsieh YC, Chang YF, Lee KH, Wu YC, Chang LK* (2010) Inhibition of the Epstein-Barr virus lytic cycle by moronic acid. Antiviral Res. 85(3):490-495. (*Correspondence)