國立中興大學基因體暨生物資訊學研究所

　　

　　 　　

　　　　　　　

　　　　　　　

　　　　　　　

基因體暨生物資訊學研究所

Graduate Institute of Genomics and Bioinformatics

Chinese
English

興大首頁

National Chung Hsing University

醫科博班

Doctoral Program in Medical Biotechnology

生命科學院

College of Life Sciences

劉俊宏

研究室:結構生物資訊核心實驗室

榮譽

時間 內容
2006/07 “Glycosphingolipid-facilitated membrane insertion and internalization of cobra cardiotoxin: crystal structure of the cardiotoxin/sulfatide complex.”
中央研究院分子生物研究所 學生/助理/博士後申請出席國際學術會議獎助
2004/10 “Crystal structure of PriB, a primosomal DNA replication protein of Escherichia coli.”
國家同步輻射研究中心第十屆用戶年會暨研討會 學生口頭報告比賽第二名與壁報比賽佳作
2004/05 “Crystal structure of PriB, a primosomal DNA replication protein of Escherichia coli.”
第九屆生物物理新知研討會青年學子壁報論文獎第二名

簡要經歷

職稱 服務單位 起訖年月
副教授 中興大學基因體暨生物資訊所 2020/08 – 迄今
合聘助理教授 中興大學生物技術學研究所 2008/08 – 迄今
專任助理教授 中興大學基因體暨生物資訊所 2009/02 – 2020/07
助理教授 台灣生物物理學會 2007/05 –
兼任助理教授 國立中興大學 生物技術學研究所 2007/02 –
合聘助理教授 國立中興大學 生命科學系 2007/02 -迄今
專任助理教授 國立中興大學 生物科技發展中心 2008/08 -迄今
博士後研究員 中央研究院 分子生物研究所 2006/01 – 2007/01
博士 國防醫學院、中央研究院、國家衛生研究院合辦生命科學研究所 2001/08 – 2005/12
碩士 國立陽明大學 遺傳學研究所 1995/09 – 1997/06
學士 台北醫學院 藥學系 1991/09 – 1995/06

專業訓練

內容
  1. 美國結晶學會暑期訓練課程「Summer course in crystallography」蛋白質結構與功能(Structure and function of proteins) 美國喬治亞大學 (2001/06)

學術演講

內容
  1. “Glycosphingolipid-facilitated membrane insertion and internalization of cobra cardiotoxin: crystal structure of the cardiotoxin/sulfatide complex.”美國結晶學會 2006 年年會「環太平洋地區X光與中子設施的科學研究」議程 (2006/07)

教學與研究

開設課程     [教材下載]
  • [大學部] 生物化學
  • [大學部] 生物技術
  • [研究所] 研究所
  • [研究所] 專題討論
  • [研究所] 生物化學特論
  • [研究所] 應用基因體學及生物資訊學暨實習
  • [研究所] 蛋白質工程學
  • [研究所] 蛋白質分子模擬及理論藥物設計
  • [生技博士班] 生物化學特論
  • [生技博士班] 技術特論
  • [通識教育講座] 生命科學與人生
  • [暑期核心課程學分班] 生物資訊學在生命科學上之應用暨實習
  • [暑期核心課程學分班] 功能蛋白質體學暨實習
  • [暑期核心課程學分班] 基因體學

 

研究專長
  1. 蛋白質結構解析
  2. 結構生物資訊學
  3. 生物分子X光晶譜學

研究主題

實驗室研究方向    [詳細內容]

研究主題:

 

工業酵素的蛋白質結構改良 細菌抗藥性酵素的結構解析與新藥開發、真核細胞內核糖體/訊號辨識粒子/蛋白質轉位體間的交互作用、酵母菌染色質重塑複合體 RSC、果蠅 JAK/STAT 訊息傳遞途徑、鏈黴菌染色體末端蛋白

 

本實驗室目前研究以下蛋白質的結構，並探討其在生物體內的功能：

 

I. 真核細胞內核糖體/訊號辨識粒子/蛋白質轉位體間的交互作用

真核生物核糖體 (Ribosome) 蛋白 L23a 與 L35 (在原核生物內的同源蛋白為 L23 與 L29 ) 在聯繫蛋白質合成、摺疊 (Folding) 與後續運送 (Sorting) 上扮演重大的角色。因為 L23a 與 L35 剛好位在核糖體與監護蛋白 (Chaperones)、訊號辨識粒子 (Signal recognition particle, SRP) 以及蛋白質轉位體 (Translocon) Sec61 相接觸的關鍵地域。雖然近幾年來陸續解出原核核糖蛋白 L23 與 L29 的晶體結構，由於真核核糖蛋白 L23a 與 L35 不論在尺寸與序列上皆和 L23 與 L29 差異極大，十分值得深入探討 L23a 與 L35 如何協助核糖體在真核細胞內同時調控較原核細胞更為複雜的蛋白質合成、摺疊與後續運送。

 

II. 酵母菌染色質重塑複合體 RSC

在真核細胞內，基因組 (Genome) 通常被保護而包裹成染色質 (Chromatin)，以防止外來的傷害。但是，當細胞要進行去氧核糖核酸 (DNA) 的轉錄 (Transcription)、複製 (Replication)、傷害修補 (Damage repair) 與重組 (Recombination) 時，染色質會感受到細胞的訊息而改變其構造。染色質重塑複合體 (Chromatin remodeling complexes) 會利用消耗三磷酸腺苷 (ATP) 來改變核仁小體 (Nucleosomes) 的結構與分佈情形，進而重塑染色質的構造。在酵母菌 (Saccharomyces cerevisiae) 細胞內有兩組染色質重塑複合體，分別是 SWI/SNF (SWItch / Sucrose NonFermentable) 與 RSC (Remodelers of the Structure of Chromatin) 複合體。然而兩者中，只有 RSC 複合體對於酵母菌的生存與細胞週期進行是重要且必需的。RSC 複合體內至少含有 16 個蛋白質，其中部分蛋白質成員也同時參與 SWI/SNF 複合體的組成。

 

III. 果蠅 JAK/STAT 訊息傳遞途徑

由 Janus activated kinases (JAKs) 與 Signal transducers and activators of transcription (STATs) 組成的 JAK/STAT 訊息傳遞途徑引導人體內許多重要的生理程序，包含：免疫反應、血球生成、發炎現象以及神經與胚胎的發育。JAK/STAT 訊息傳遞途徑的持續活化也與人類的多種腫瘤的發生，尤其是造血系統惡性腫瘤有關。相較於人，果蠅 (Drosophila melanogaster) 體內有一套簡單的JAK/STAT 訊息傳遞途徑。目前已知其中主要成員包括：三個配體 (Unpaired：Upd、Upd2 與 Upd3)、一個細胞膜上的受器 (Domeless, Dome)、一個 JAK (Hopscotch, Hop) 與一個 STAT (STAT92E)。雖然成員簡單，卻參與了果蠅的體節生成、性別決定、免疫反應、血球生成、眼睛細胞的增生及分化、以及中樞神經、後腸與氣管的發育。

 

IV. 鏈黴菌染色體末端蛋白

鏈黴菌 (Streptomyces) 是一種普遍存在於土壤內的絲狀細菌，屬於革蘭氏陽性菌。鏈黴菌可製造出許多有價值的醫藥品，其中以種類繁多的抗生素最為人所悉。不同於一般細菌具有環形的染色體，鏈黴菌的染色體與質體的構造為直線形。鏈黴菌染色體與質體的端粒 (Telomeres) 均帶有末端蛋白 (Terminal proteins)，它們以共價鍵結合上去氧核糖核酸 (DNA) 的 5′ 端。除了保護染色體與質體的端粒構造，目前認為當鏈黴菌染色體利用本身的複製起始點 (The chromosomal origin of replication, OriC) 進行雙向複製後，末端蛋白還擔當引子 (Primer) 來補齊延遲股 (The lagging strand) 上的端點複製問題 (The end replication problem)。

著作

期刊論文 (*Corresponding author)
  1. Salem, G.M., Galula, J.U., Wu, SR.Liu, J.-H ,et al. Antibodies from dengue patients with prior exposure to Japanese encephalitis virus are broadly neutralizing against Zika virus. Commun Biol(2024)
  2. Tseng YW, Yang TJ, Hsu YL, Liu, J.-H.*, Tseng YC, Hsu TW, Lu Y, Pan SH, Cheng TR, Fang JM. Dual-targeting compounds possessing enhanced anticancer activity via microtubule disruption and histone deacetylase inhibition. Eur J Med Chem(2024)
  3. Fang, Y.-T., Lai, W.-S., Liu, J.-H.*, Liu, Y.-C.*: Enhanced cecropin B2 production via chitin-binding domain and intein self-cleavage system. Biotechnology And Applied Biochemistry(2018)
  4. Shen, W.-F., Galula, J.U., Liu, J.-H., Liao, M.-Y., Huang, C.-H., Wang, Y.-C., Wu, H.-C., Liang, J.-J., Lin, Y.-L., Whitney, M.-T., Chang, G.-J., Chen, S.-R., Wu, S.-R., Chao, D.-Y.: Epitope resurfacing on dengue virus-like particle vaccine preparation to induce broad neutralizing antibody. Elife(2018)
  5. Chiu, H.-C., Huang, W.-R., Liao, T.-L., Chi, P.-I., Nielsen, B.L., Liu, J.-H., Liu, H.-J.: Mechanistic insights into avian reovirus p17-modulated suppression of cell cycle CDK-cyclin complexes and enhancement of p53 and cyclin H interaction. Journal Of Biological Chemistry(2018)
  6. Lee, C.-Y., Lin, C.-C., Liu, Y.-L., Liu, G.-Y.*, Liu, J.-H.*, Hung, H.-C.*: Molecular interplay between the dimer interface and the substrate-binding site of human peptidylarginine deiminase 4. Scientific Report(2017)
  7. Li, C., Bai, X., Meng, R., Shaozhou, W., Zhang, Q., Hua, R., Liu, J.-H., Liu, M., Zhang, Y.*: Identification of a new broadly cross-reactive epitope within domain III of the duck Tembusu virus E protein. Scientific Reports(2016)
  8. Li, C., Liu, J., Shaozhou, W., Bai, X., Zhang, Q., Hua, R., Liu, J.-H.*, Liu, M.*, Zhang, Y.*: Epitope identification and application for diagnosis of duck Tembusu virus infections in ducks. VIRUSES-BASEL(2016)
  9. Kuo, T.-C., Li, L.-W., Pan, S.-H.*, Fang, J.-M.*, Liu, J.-H., Cheng, T.-J., Wang, C.-J., Hung, P.-F., Chen, H.-Y., Hong, T.-M., Hsu, Y.-L., Wong, C.-H., Yang, P.-C.: Purine-type compounds induce microtubule fragmentation and lung cancer cell death through interaction with katanin. Journal of Medicinal Chemistry(2016)
  10. Chen, J.-C., Liu, J.-H., Hsu, D.-W., Shu, J.-C., Chen C.-Y., Chen, C.-C.*: Methylatable signaling helix coordinated inhibitory receiver domain in sensor kinase modulates environmental stress response in Bacillus cereus. PLoS One(2015)
  11. Hsieh, J.-Y., Li, S.-Y., Tsai, W.-C., Liu, J.-H., Lin, C.-L., Liu, G.-Y.*, Hung, H.-C.*: A small-molecule inhibitor suppresses the tumor-associated mitochondrial NAD(P)+-dependent malic enzyme (ME2) and induces cellular senescence. Oncotarget(2015)
  12. Lin, H.-Y., Liu, J.-H., Cheng, K.-L., Lin, J.-Y., Liu, N.-R., Meng, M.-H.*: A novel binding of GTP stabilizes the structure and modulates the activities of human phosphoglucose isomerase/autocrine motility factor. Biochemistry and Biophysics Reports(2015)
  13. Hsieh, J.-Y., Li, S.-Y., Chen, M.-C., Yang, P.-C., Chen, H.-Y., Chan, N.-L.*, Liu, J.-H.*, Hung, H.-C.*: Structural characteristics of the nonallosteric human cytosolic malic enzyme. BIOCHIMICA ET BIOPHYSICA ACTAPROTEINS AND PROTEOMICS(2014)
  14. Hsieh, J.-Y., Liu, J.-H., Yang, P.-C., Lin, C.-L., Liu, G.-Y.*, Hung, H.-C.* (2014, Jun). :Fumarate analogs act as allosteric inhibitors of the human mitochondrial NAD(P)+-dependent malic enzyme.PLoS One
  15. 1. Chepyshko, H., Lai, C.-P., Huang, L.-M., Liu, J.-H., and Shaw, J.-F. (2012, Jul.) Multifunctionality and diversity of GDSL esterase/lipase gene family in rice (Oryza sativa L. japonica) genome: new insights from bioinformatics analysis. BMC Genomics 13, 309 doi:10.1186/1471-2164-13-309 (SCI, IF2011=4.073 Times cited :8)
  16. Hsieh, J.-Y., Liu, J.-H., Fang, Y.-W., Hung, H.-C. (2009, May.) Dual roles of Lys57 at the dimer interface of human mitochondrial NAD(P)+-dependent malic enzyme. Biochem. J. 402, 201-9. (SCI, IF2007=4.009 Times cited :0)
  17. Li, T.-N., Chin, K.-H., Liu, J.-H., Wang, A H.-J., Chou, S.-H. (2009, May.) XC1028 from Xanthomonas campestris adopts a PilZ domain-like structure without a c-di-GMP switch. Proteins. 75, 282-8. (SCI, IF2007=3.354 Times cited :0)
  18. Chou, C.-C., Chang, C.-W., Liu, J.-H., Chen, L.-F., Hsiao, C.-D., Chen, H.-W. (2007, Sep.) Small Ubiquitin-like Modifier Modification Regulates the DNA Binding Activity of Glial Cell Missing Drosophila Homolog a. J. Biol. Chem. 282, 27239-49. (SCI, IF2006=5.808 Times cited :3)
  19. Wang, C.-H.*, Liu, J.-H.*, Lee, S.-C., Wu, W.-g., and Hsiao, C.-D. (2006, Jan.) Glycosphingolipid-facilitated membrane insertion and internalization of cobra cardiotoxin: the sulfatide/cardiotoxin complex structure in a membrane-like environment suggests a lipid-dependent cell-penetrating mechanism for membrane binding polypeptides. J. Biol. Chem. 281, 656-77.(SCI, IF 2006=5.808; Times cited: 15) *These authors contributed equally to this work.
  20. Liu, J.-H., Chang, T.-W., Huang, C.-Y., Chen, S.-U., Wu, H.-N., Chang, M.-C., Hsiao, C.-D. (2004, Nov.) Crystal structure of PriB, a primosomal DNA replication protein of Escherichia coli. J. Biol. Chem. 279, 50465-71. (SCI, IF2006=5.808 Times cited : 5)
  21. Forouhar, F., Huang, W.-N., Liu, J.-H., Chien, K.-Y., Wu, W.-g. and Hsiao, C.-D. (2003, Jun.) Structural basis of the membrane-induced cardiotoxin A3 oligomerization. J. Biol. Chem. 278, 21980-8. (SCI, IF2006=5.808 Times cited :21)[PDB]
  22. Liu, J. H., Liao, Y. D., Sun Y. J. (2001, Nov.) Crystallization and preliminary X-ray diffraction analysis of cytotoxic ribonucleases from bullfrog Rana catesbeiana. Acta Crystallogr. D57, 1697-9. (SCI, IF2006=1.687 Times cited :0)

 

研討會論文 (*Invited speaker)
  1. Liu, J.-H., Lee, Y.-P., Yang, J.-Y.: The Crystal Structure of the N-terminally Deleted Type III Effector protein XopAI. The 23th Biophysics Conference.
  2. Liu, J.-H., Lee, C.-Y., Lin, C.-C., Liu, Y.-L., Liu, G.-Y., Hung, H.-C.: Molecular Dynamics Study on the Interaction between Dimer Interface and Substrate-Binding Site of Human Peptidylarginine Deiminase 4. The 22th Biophysics Conference.
  3. Liu, J.-H.: Replica exchange molecular dynamics method for Trp-cage folding simulation in implicit solvent. The 20th Biophysics Conference.
  4. Peng, L.-W., Chen, Y.-T., and Liu, J.-H.: Crystallization of Dps protein from Klebsiella oxytoca The 20th NSRRC Users’ Meeting.
  5. Lin, C.-W., Hung, H.-C., and Liu, J.-H.: Crystallization of human cytosolic NADP+-dependent malic enzyme complexed with cofactor and substrates. The 20th NSRRC Users’ Meeting.
  6. Chen, C.-W., Shen, G.-H., Chen, J.-H., and Liu, J.-H.(2013, Nov) Virtual screening and experimental verification to identify potential inhibitors of the Erm(41) methyltransferase responsible for bacterial resistance against macrolide antibiotics. 台灣生物化學及分子生物學學會2013年冬令營. (Poster)
  7. Peng, L.-W., Chen, Y.-T. and Liu, J.-H.. (2013, Sep) Crystallization of β-lactamase like protein from Klebsiella oxytoca E718. The 19th NSRRC Users’ Meeting. (Poster)
  8. Liu, J.-H., Chen, C. K.-M., Chang, S.-W., Shaw, J.-F., Wang, A. H.-J., and Liu, J.-H. (2012, Oct.) Preliminary X-ray crystallographic analysis of trehalose synthase from Deinococcus radiodurans. The 18th NSRRC Users’ Meeting. (Poster)
  9. Chen, J.-W., Nien, C.-Y., Chen, C. K.-M., Chang, S.-W., Shaw, J.-F., Wang, A. H.-J., and Liu, J.-H.(2012, Oct.) Preliminary X-ray crystallographic analysis of trehalose synthase from Picrophilus torridus. The 18th NSRRC Users’ Meeting. (Poster)
  10. Nien, C.-Y., Cheng, C.-Y., Liu, J.-H., Shaw, J.-F., and Chen, Y.-T. (2012, May.) Crystal structure of glutaredoxin from Chlorella sorokiniana T-89. The 17th Biophysics Conference. (Poster)
  11. Hung, S.-J. and Liu, J.-H. (2012, May.) Design of an accurate predictor for the thermostable protein design in PERT server. The 17th Biophysics Conference. (Poster)
  12. Wu, J.-E., Chiu, S.-W., Yang, J.-Y., and Liu, J.-H. (2012, Mar.) Crystal structure of XopAI from Xanthomonas axonopodis pv. citri. 2012 International Conference on c-di-GMP and Xanthomonads. (Poster)
  13. Hung, S.-J. andLiu, J.-H. (2011, Dec.) PERT: an integrated informatics platform for thermostable protein design. 2011 Taiwan Enzyme Mechanism Conference. (Poster)
  14. Nien, C.-Y., Cheng, C.-Y., Shaw, J.-F., Chen, Y.-T., and Liu, J.-H. (2011, Oct.) Crystallization and preliminary X-ray crystallographic analysis of Chlorella glutaredoxin. The 17th NSRRC Users’ Meeting. (Poster)
  15. Wu, J.-E., Chiu, S.-W., Yang, J.-Y., and Liu, J.-H. (2010, Oct.) Crystallization and preliminary X-ray crystallographic analysis of XopAI from Xanthomonas axonopodis pv. citri. The 16th NSRRC Users’ Meeting. (Poster)
  16. Liu, J.-H., Hong, C.-S., Chang, S.-W., and Shaw, J.-F. (2009, Nov.) Investigation of the structural basis for thermostability of trehalose synthase from Picrophilus torridus. The 5th International Symposium on Biocatalysis and Biotechnology. (Poster)
  17. Hsu, Y.-J. and Liu, J.-H. (2009, Oct.) Effects of trimethylamine-N-oxide (TMAO) on the interactions of lysozyme in crystal. The 15th NSRRC Users’ Meeting. (Poster)