張智芬

張智芬 Ph.D. Zee-Fen Chang

講座教授 Chair 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. 288590(office), 288591(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

2026 115學年度臺大講座

2026 財團法人吳健雄學術基金會2026年第19屆台灣傑出女科學家獎之傑出獎

2024 中華民國斐陶斐榮譽學會第29屆傑出成就獎

2023 第26屆教育部國家講座獎

2023 112學年度臺大講座

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
博士班學生：崔李孝婧
碩士班學生：蔡昀、蔣宜儒、王士怡、李承蕙、林俊彬
研究助理：王心彥、陳奕廷、陳羿涵
行政助理：葉泳沁

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、廖偉廷、趙彤

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、邢芃、黃宣榕、范竣翔、何珮瑄、蘇琪、蘇柏羽、邱璟筠、丁誠緯、張舒婷、陳羿涵、陳映蓉

  1. Chen CW, Liao WT, Chao T, Chen YH, Weng SC, Shiao SH, Kao CY, Li YJ, Cheng KA & Chang ZF*. An engineered viral RNA degrader on mitochondrial surface that mitigates RNA virus infection. Nature Communications, DOI：10.1038/s41467-026-73487-1.
  2. Chen CW, Chen YJ, Cuili XJ, Chen YH & Chang ZF*. PRKN activation for mitophagy requires an NME3-regulated phosphatidic acid signal that separates mitochondria from endoplasmic reticulum tethering. Autophagy 22(5):963-981.
  3. Huang HC, Chung YH, Wu SY, Wang HY, Lin CY, Yang TJ, Fang JM, Hu CM, Chang ZF*. Glutathione determines chronic myeloid leukemia vulnerability to an inhibitor of CMPK and TMPK. Commun Biol 7, 843 (2024).
  4. Chen CW, Su C, Huang CY, Huang XR, Cuili X, Chao T, Fan CH, Ting CW, Tsai YW, Yang KC, Yeh TY, Hsieh ST, Chen YJ, Feng Y, Hunter T, Chang ZF*. NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia. Nature communications (2024)15:2264.
  5. Liao WT, Chiang YJ, Yang-Yen HF, Hsu LC, Chang ZF*, Jeffrey J Y Yen. CBAP regulates the function of Akt-associated TSC protein complexes to modulate mTORC1 signaling. J Biol Chem. 2023 Dec;299(12):105455.
  6. Su YA, Chiu HY, Chang YC, Sung CJ, Chen CW, Reika Tei, Huang XR, Hsu SC, Lin SS, Wang HC , Lin YC, Hsu JC, Hermann Bauer, Yuxi Feng, Jeremy M Baskin, Chang ZF*, Liu YW. NME3 binds to phosphatidic acid and mediates PLD6-induced mitochondrial tethering. J Cell Biol (2023) 222 (10): e202301091. (Co-corresponding author).
  7. Shih HS, Chen WY, Wang HY, Chao T, Huang HD, Chou CH, and Chang ZF*. DNMT3b protects centromere integrity by restricting R-loop-mediated DNA damage. Cell Death and Disease (2022) 13:546 ; https://doi.org/10.1038/s41419-022-04989-1.
  8. Wang HY, Hsin P, Huang CY, Chang ZF*. A convenient and sensitive method for deoxynucleoside triphosphates quantification by the combination of RCA and qPCR. Anal. Chem. 93: 14247-14255, 2021.
  9. Lai JH, Wu DW, Wu CH, Hung LF, Huang CY, Ka SM, Chen A, Chang ZF*, Ho LJ. Mitochondrial CMPK2 mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways. iScience 24(6),102498.
  10. 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 17:3444-3460, 2021.
  11. Honsho M, Abe Y, Imoto Y, Chang ZF*, Mandel H, Falik-Zaccai TC, Fujiki Y. Mammalian Homologue NME3 of DYNAMO1 Regulates Peroxisome Division. International Journal o f Molecular Sciences, 21:8040-8060, 2020.
  12. 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.
  13. Huang CY, Yagüe-Capilla M, González-Pacanowska D and Chang ZF*. Quantitation of deoxynucleoside triphosphates by click reactions. Sci. Rep. 10:611, 2020.
  14. 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).
  15. 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 cell survival underlie a neurodegenerative disorder. Proc. Natl. Acad Sci USA 116: 566-574, 2019.
  16. 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.
  17. Wei CW, Lee CY, Lee DJ, Chu CF, Wang JC, Wang TC, Jane WN, Chang ZF*, Leu CM, Dzhagalov IL, Hsu CL. Equilibrative Nucleoside Transporter 3 Regulates T Cell Homeostasis by Coordinating Lysosomal Function with Nucleoside Availability. Cell Reports. 23:2330-2341,2018.
  18. Chuang TY, Cheng AJ, Chen IT, Lan TY, Huang IH, Shiau CW, Hsu CL, Liu YW, Chang ZF, Tseng PH, Kuo JC. Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone. Oncotarget. 8:49735-49748,2017.
  19. Guo JR, Chen QQ, Lam CW, Wang CY, Wong VK, Chang ZF, Zhang W. Profiling ribonucleotide and deoxyribonucleotide pools perturbed by gemcitabine in human non-small cell lung cancer cells. Scientific Reports. 6:37250,2016.
  20. Chen YH, Hsu HY, Yeh MT, Chen CC, Huang CY, Chung YH, Chang ZF, Kuo WC, Chan NL, Weng JH, Chung BC, Chen YJ, Jian CB, Shen CC, Tai HC, Sheu SY, Fang JM. Chemical Inhibition of Human Thymidylate Kinase and Structural Insights into the Phosphate Binding Loop and Ligand-Induced Degradation. Journal of Medicinal Chemistry. 59:9906-9918,2016.
  21. Chen CH, Tsao N, Huang LY, Yen Y, Liu X, Lehman C, 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.
  22. Wu TH, Kuo YY, Lee HH, Kuo JC, Ou MH & Chang ZF. Epigenetic repression of ribosomal RNA transcription by ROCKdependent aberrant cytoskeletal organization. Scientific Reports. 6:28685,2016.
  23. Tsao N, Yang YC, Deng YJ, and Chang ZF. The direct interaction of NME3 with Tip60 in DNA repair. Biochem. J. 473:1237-45,2016. 
  24. 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. NATURE COMMUNICATIONS. 7:10420,2016. 

  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