張智芬

張智芬 Ph.D. Zee-Fen Chang

特聘教授 Distinguished Professor

研究領域:
核酸代謝與DNA修復
Nucleotide metabolism in DNA damage

研 究 室:
基礎醫學大樓1539室
Basic Medicine Building 1539

Tel:886-2-23123456 ext. 88590(office), 88591(Lab)

The mammalian genomes are comprised of nuclear DNA and hundreds of copies of mitochondrial DNA. In one’s lifetime, DNA lesions in the genome are constantly generated due to endogenous and exogenous exposure to genotoxic chemicals from all sources. Removal of these DNA damages with correct and sufficient nucleotide incorporation is essential for maintaining the genome stability, which has a consequent impact on health and disease. We are interested in how nucleotide regulation is coupled with DNA damage responses to dictate genome integrity and mito-nuclear communication in normal and cancer cells. Our long-termed goal is to develop novel therapeutic and prevention strategies against diseases by manipulating DNA metabolism separately in nuclei and mitochondria through targeting nucleotide enzymes and their regulatory pathways

1979 B.S., Department of Agricultural Chemistry, National Taiwan University
1981 M.S., Department of Agricultural Chemistry, National Taiwan University
1986 Ph.D., Department of Biochemistry, Rutgers the State University of New Jersey, U.S.A.

Professional Experiences

1986-1988 Post-doc, Program of Mol.Biol., Michigan Cancer Foundation, U.S.A.

1988-1996 Associate professor, Department of Biochemistry, Chang Gung University

1996-1997 Professor, Department of Biochemistry, Chang Gung University, Taiwan

1997-2006 Professor, Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University

2006-2010 Tenure Distinguished Professor, Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University

2010-2011 Deputy Dean, College of Life Sciences, National Yang-Ming University

2011-2015 Director, Institute of Biochemistry and Molecular Biology, National Yang-Ming University 

2010-2016 Distinguished Professor, Institute of Biochemistry and Molecular Biology, National Yang-Ming University

2016-present Distinguished Professor, Institute of Molecular Medicine, National Taiwan University

2020-present Adjunct Researcher, Genome Research Center, Academia Sinica

 

Honor

2015 科技部傑出特約研究員獎

2013 教育部教育部第57屆學術獎

2013 台灣醫學會杜聰明博士紀念演講獎

2004 行政院國家科學委員會國科會研究傑出獎

2002 財團法人青杏醫學文教基金會第十三屆青杏醫學獎

1999 行政院國家科學委員會國科會研究傑出獎

1996 行政院國家科學委員會國科會研究傑出獎

實驗室成員:
博士後研究員:陳志威、施雪姿、黃常宇
博士班學生:趙彤
碩士班學生:邢芃、黃宣榕、范竣翔、何珮瑄
研究助理:王心彥
行政助理:譚康居

Alumni:
博士:賴金美、李家隆、黃婷茵、柯博元、李曉暉、周玟伶、郭遠燁、張元貞、胡春美、陳彥鴒、田穗稺、李明祥、柯玫如、曹甯、莊鄉灝、吳澤祥、陳志威、王鴻聆、黃常宇

碩士:胡淑芬、黃爾毅、周玟伶、呂靜怡、蔡宜君、黎欣怡、鄔書林、楊哲權、謝嘉凌、張元貞、劉佳宜、林大為、胡春美、張益昌、許弼強、王致權、呂宗翰、鍾政光、張家芸、黃婷筠、葉斯尹、謝明芸、黃奕璇、黃常宇、鄧伃君、趙彤、黃琳翊、黃承煒、鍾映玄、吳詣晟、杜宜蓁、劉炘莓

  1. Chao T, Shih ST, Hsu SC, Chen PJ, Fan YS, Jeng YM, Shen ZQ, Tsai TF, and Chang ZF. Autophagy Restricts Mitochondrial DNA damage-induced Release of Endonuclease G to Regulate Genome Stability. Autophagy. (Accepted).
  2. Chen CW, Tsao N, Zhang W. and Chang ZF. NME3 Regulates Mitochondria to Reduce ROS-Mediated Genome Instability. Int. J. Mol. Sci 21:5048, 2020.
  3.  Huang CY, Yagüe-Capilla M, González-Pacanowska D and Chang ZF: Quantitation of deoxynucleoside triphosphates by click reactions. Sci. Rep. (2020) 10:611
  4.  Huang CY, Chen YC, Wu-Hsieh BA, Fang JM, Chang ZF. The Ca-loop in thymidylate kinase is critical for growth and contributes to pyrimidine drug sensitivity of Candida albicans J. Biol. Chem. 294:10686-10697, 2019 (Selected for a special virtual issue focusing on antibiotic activities and mechanisms of resistance).
  5. Chen CW, Wang HL, Huang CW, Huang CY, Lim WK, Tu IC, Koorapati A, Hsieh ST, Kan HW, Tzeng SR, Liao JC, Chong WM, Naroditzky I, Kidron D, Eran A, Nijim Y, Sela E, Feldman HB, Kalfon L, Raveh-Barak H, Falik-Zaccai TC, Elpeleg O, Mandel H, Chang ZF. Two separate functions of NME3 critical for survival underlie a neurodegenerative disorder. Proc. Natl. Acad Sci USA 116: 566-574, 2019.
  6. Hu CM, Tsao N, Wang YT, Chen YJ, Chang ZF. Thymidylate kinase is critical for DNA repair via ATM-dependent Tip60 complex formation. FASEB J. 33: 2017-2025, 2019.
  7. Chen CH, Tsao N, Huang LY, Yen Y, Liu X, LehmanC, Wang YH, Tseng MC, Chen YJ, Ho YC, Chen CF, and Chang ZF. The impact of dUTPase on ribonucleotide reductase-induced genome instability in cancer cells. Cell Reports,16:1287, 2016.
  8. Wu TH, Kuo YY, Lee HH, Kuo JC, Ou MH and Chang ZF. Epigenetic repression of ribosomal RNA transcription by ROCK-dependent aberrant cytoskeletal organization. Scientific Reports 6:28685, 2016.
  9. Tien, SC, Lee HH, Yang YC, Lin MH, Chen, YJ, Chang, ZF The Shp2-induced epithelial disorganization defect is reversed by HDAC6 inhibition independent of Cdc42. Nat. Commun. 7:10420, 2016.
  10. Wang HL, Yang CH, Lee HH, Kuo JC, Her SS, Chien S, Lee KS, Hung SC, Chang ZF, Dexamethasone-induced SGK1 increases Sec5/GEF-H1 interaction essential for adhesion-mediated tension. J. Cell Sci. 128: 3757, 2015.
  11. Lee MH, Wang L, and Chang ZF. The contribution of mitochondrial thymidylate synthesis in preventing the nuclear genome stress. Nucleic Acids Research, 42: 4972-4984, 2014
  12. Tien SC and Chang ZF. Oncogenic Shp2 disturbs microtubule regulation to cause HDAC6-dependent ERK hyperactivation. Oncogene. 33 2938-2946,2014
  13. Hu CM , Yeh MT , Tsao N , Chen C-W, Gao QZ , Chang CY, Lee MH , Fang JM , Sheu SY , Lin CJ , Tseng MC , Chen YJ , and Chang ZF. Tumor Cells Require Thymidylate Kinase to Prevent dUTP Incorporation during DNA Repair. Cancer Cell. 22, 36-50, 2012 (selected for preview in the issue).
     

  1. 標靶人類胸腺核甘酸激酶誘導惡性腫瘤中的DNA修復毒性,中華民國,I445696 2014.07.21-2031.11.23
  2. 偵測ROCK活性之試劑, 中華民國, I420674, 2014.11.11-2032.07.23
  3. 偵測ROCKs活化之試劑,美國, US9,017,952 B2, 2015.04.28-2033.01.02
  4. TARGETING HUMAN THYMIDYLATE KINASE INDUCES DNA REPAIR TOXICITY IN MALIGNANT TUMOR CELLS,美國,申請案號:13/990,398
  5. 标靶人类胸腺核苷酸激酶诱导恶性肿瘤中的DNA修复毒性,中國,申請案號: 201180057410.4