陳光超老師實驗室

蛋白質酪氨酸去磷酸酶在發育與腫瘤發生的功能研究

蛋白質酪氨酸去磷酸酶(Protein Tyrosine Phosphatases, PTPs)是一群受到嚴密調控的酵素， 並且在各種不同的過程中與蛋白質酪氨酸磷酸酶(Protein Tyrosine Kinase, PTK)協同控制蛋白質的磷酸化。目前許多的證據指出，在腫瘤發生及個體發育過程當中，蛋白質磷酸化的調控扮演重要的角色。我們使用PTPome 作為研究PTP在癌症及發育的一個模式，並利用質譜為基礎的受質捕獲方法找尋dPtpmeg/PTPN3酪氨酸去磷酸酶的潛在受質。遺傳與生化實驗分析指出，dPtpmeg和PTPN3分別能調節果蠅和哺乳動物細胞中表皮生長因子受體酪氨酸蛋白激酶受質15(Eps15)的酪氨酸磷酸化狀態。表皮生長因子受體（EGFR）屬於酪氨酸激酶受體家族，參與在調節細胞的存活，增殖，分化，遷移和腫瘤發生。我們探討PTPN3在表皮生長因子受體訊息傳導的分子調控機制及在表皮生長因子受體相關的非小細胞肺癌形成的角色。這項研究的結果對於表皮生長因子受體所導致腫瘤，提供具潛力的新治療干預措施。

細胞自噬作用(Autophagy)訊息傳遞網路之功能研究

細胞自噬作用(Autophagy)為調控細胞存活與凋亡的重要機轉。當個體細胞遇到生存壓力時，會自行發展出包膜企圖吞食或分解胞內的物質，以保全細胞 存活的自我保護機制。近年來科學家也發現，細胞自噬作用與生物發育以及許多人類疾病，例如腫瘤、感染與免疫、及神經退化性疾病密切相關。藉由生化與分子遺傳實驗我們最近的研究發現一新的Atg9膜蛋白調控之訊息傳遞路徑。利用氧化壓力下的果蠅腸道細胞為模式系統，我們發現Atg9會與腫瘤壞死因子受體相關因子(dTRAF2/TRAF6)結合作用，活化JNK訊息傳遞及啟動下游的氧化壓力防護機制，包含細胞自噬、細胞凋亡、以及促進幹細胞增生。另外，我們更進一步發現受氧化壓力活化的細胞自噬會透過負回饋機制抑制JNK訊息傳遞，避免防護機制過度活化，以維持在氧化壓力下組織的恆定性。這些研究成果可能提供治療細胞自噬失調和氧化壓力等相關疾病新的思考方向。

經歷

• 2021 – 迄今   研究員, 中央研究院生化所
• 2013 – 迄今   合聘副教授, 臺灣大學生化科學研究所
• 2013 – 2021   副研究員, 中央研究院生化所
• 2007 – 2013   兼任助理教授, 臺灣大學生化科學研究所
• 2006 – 2012   助研究員, 中央研究院生化所
• 1998 – 2005   博士後研究, 美國麻州總院癌症研究中心及哈佛大學醫學院

學歷

• 1997   博士, 分子遺傳, 美國德州大學奧斯汀分校

1. Tzou FY, Wen JK, Yeh JY, Huang SY, (Chen GC)*, Chan CC*  (2021-12 accepted)  IUBMB life  "Drosophila as a model to study autophagy in neurodegenerative diseases and digestive tract."
   
2. Muthusamy S, Jan HM, Hsieh MY, Mondal S, Liu WC, Ko YA, Yang WY, Mong KT, (Chen GC), Lin CH*  (2021-10)  Journal of biomedical science  28(1), 72  "Enhanced enzymatic production of cholesteryl 6\'-acylglucoside impairs lysosomal degradation for the intracellular survival of Helicobacter pylori."
   
3. Chou HY, Lee YT, Lin YJ, Wen JK, Peng WH, Hsieh PL, Lin SY, Hung CC, (Chen GC)  (2021-10)  Autophagy  17(10), 2750-2765  "PTPN9-mediated dephosphorylation of VTI1B promotes ATG16L1 precursor fusion and autophagosome formation."
   
4. Klionsky DJ, (Chen GC), Chen RH, Yang WY et al.  (2021-02)  Autophagy  17(1), 1-382  "Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)."
   
5. Chen YH, Huang TY, Lin YT, Lin SY, Li WH, Hsiao HJ, Yan RL, Tang HW, Shen ZQ, (Chen GC), Wu KP, Tsai TF, Chen RH*  (2021-02)  Nature Communications  12(1), 1322  "VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism."
   
6. Amartuvshin O, Lin CH, Hsu SC, Kao SH, Chen A, Tang WC, Chou HL, Chang DL, Hsu YY, Hsiao BS, Rastegari E, Lin KY, Wang YT, Yao CK, (Chen GC), Chen BC, Hsu HJ  (2020-07)  Aging cell  19(8), e13191  "Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss."
   
7. Deretic V, Prossnitz E, Burge M, Campen MJ, Cannon J, Liu KJ, Hall P, Sklar LA, Allers L, Mariscal L, Garcia SA, Baehrecke EH, Behrends C, Cecconi F, Codogno P, (Chen GC), Elazar Z, Eskelinen EL, Fourie B, Gozuacik D, Hong W, Jo EK, Johansen T, Juhász G, Kimchi A, Ktistakis N, Kroemer G, Mizushima N, Münz C, Reggiori F, Rubinsztein D, Ryan K, Schroder K, Shen HM, Simonsen A, Tooze SA, Vaccaro M, Yoshimori T, Yu L, Zhang H, Klionsky DJ.  (2019-10)  Autophagy  15(10), 1829-1833  "Autophagy, Inflammation, and Metabolism (AIM) Center in its second year."
   
8. Li MY, Peng WH, Wu CH, Chang YM, Lin YL, Chang GD, Wu HC, (Chen GC)  (2019-10)  ONCOGENE  38(44), 7002-7016  "PTPN3 suppresses lung cancer cell invasiveness by counteracting Src-mediated DAAM1 activation and actin polymerization."
   
9. Deretic V, Prossnitz E, Burge M, Campen MJ, Cannon J, Liu KJ, Sklar LA, Allers L, Garcia SA, Baehrecke EH, Behrends C, Cecconi F, Codogno P, (Chen GC), Elazar Z, Eskelinen EL, Fourie B, Gozuacik D, Hong W, Hotamisligi G, Jaattela M, Jo EK, Johansen T, Juhasz G, Kimchi A, Ktistakis N, Kroemer G, MIzushima N, Munz C, Reggiori F, Rubinsztein D, Ryan K, Schroder K, Simonsen A, Tooze S, Vaccaro M, Yoshimori T, Yu L, Zhang H, Klionsky DJ  (2018-06)  Autophagy  14(6), 925-929  "Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence: supporting the next generation of autophagy researchers and fostering international collaborations."
   
10. Wen JK, Wang YT, Chan CC, Hsieh CW, Liao HM, Hung CC, (Chen GC)  (2017-11)  eLife  6, e29338  "Atg9 antagonizes TOR signaling to regulate intestinal cell growth and epithelial homeostasis in Drosophila"
    
11. Chen BH, Yang HJ, Chou HY, (Chen GC), Yang WY  (2017-02)  Methods in molecular biology  1560, 231-236  "Staining of Lipid Droplets with Monodansylpentane."
    
12. Klionsky DJ, (Chen GC), Yang WY et al.  (2016-01)  Autophagy  12(1), 1-222  "Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)."
    
13. Su MY, Peng WH, Ho MR, Su SC, Chang YC, (Chen GC), Chang CI  (2015-09)  Autophagy  11(9), 1580-1593  "Structure of yeast Ape1 and its role in autophagic vesicle formation."
    
14. Li MY, Lai PL, Chou YT, Chi AP, Mi YZ, Khoo KH, Chang GD, Wu CW, Meng TC, (Chen GC)  (2015-07)  Oncogene  34(29), 3791-3803  "Protein tyrosine phosphatase PTPN3 inhibits lung cancer cell proliferation and migration by promoting EGFR endocytic degradation"
    
15. Shen WC, Li HY, (Chen GC), Chern Y, Tu PH  (2015-04)  Autophagy  11(4), 685-700  "Mutations in the ubiquitin-binding domain of OPTN/optineurin interfere with autophagy-mediated degradation of misfolded proteins by a dominant-negative mechanism"
    
16. Chen KE, Li MY, Chou CC, Ho MR, (Chen GC), Meng TC, Wang AH  (2015-04)  Structure  23(4), 653-664  "Substrate Specificity and Plasticity of FERM-Containing Protein Tyrosine Phosphatases."
    
17. Kao C, Chao A, Tsai CL, Chuang WC, Huang WP, (Chen GC), Lin CY, Wang TH, Wang HS, Lai CH.  (2014-11)  Cell Death & Disease  5(11), e1510  "Bortezomib enhances cancer cell death by blocking the autophagic flux through stimulating ERK phosphorylation."
    
18. Wang CH, (Chen GC), Chien CT  (2014-09)  Biochemical and Biophysical Research Communications  452(3), 369-375  "The deubiquitinase Leon/USP5 regulates ubiquitin homeostasis during Drosophila development"
    
19. Santhanam A, Peng WH, Yu YT, Sang TK, (Chen GC)*, Meng TC*.  (2014-05)  Mol Cell Biol.  34(9), 1594-1606  "Ecdysone-induced receptor tyrosine phosphatase PTP52F regulates Drosophila midgut histolysis by enhancement of autophagy and apoptosis."
    
20. Hong-Wen Tang, Hsiao-Man Liao, Wen-Hsin Peng, Hong-Ru Lin, Chun-Hong Chen, (Guang-Chao Chen)  (2013-12)  Developmental Cell  27(5), 489-503  "Atg9 Interacts with dTRAF2/TRAF6 to Regulate Oxidative Stress-Induced JNK Activation and Autophagy Induction"
    
21. Chang YC, Tang HW, Liang SY, Pu TH, Meng TC, Khoo KH, (Chen GC)  (2013-05)  JOURNAL OF PROTEOME RESEARCH  12(5), 2138-2150  "Evaluation of Drosophila metabolic labeling strategies for in vivo quantitative proteomic analyses with applications to early pupa formation and amino acid starvation."
    
22. Santhanam A, Liang SY, Chen DY, (Chen GC)*, Meng TC*  (2013-01)  The FEBS Journal  280(2), 476-488  "Midgut-enriched receptor protein tyrosine phosphatase PTP52F is required for Drosophila development during larva-pupa transition."
    
23. Chen SF, Kang ML, Chen YC, Tang HW, Huang CW, Li WH, Lin CP, Wang CY, Wang PY*, (Chen GC)*, Wang HD*  (2012)  JOURNAL OF BIOMEDICAL SCIENCE  19(1), 52  "Autophagy-related gene 7 is downstream of heat shock protein 27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila."
    
24. Klionsky DJ, (Chen GC), Yang WY et al.  (2012)  Autophagy  8(4), 445-544  "Guidelines for the use and interpretation of assays for monitoring autophagy."
    
25. Chen DY, Li MY, Wu SY, Lin YL, Tsai SP, Lai PL, Lin YT, Kuo JC, Meng TC, (Chen GC)  (2012)  JOURNAL OF CELL SCIENCE  125(20), 4841-4852  "The Bro1-domain-containing protein Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration."
    
26. Wu PR, Tsai PI, (Chen GC), Chou HJ, Huang YP, Chen YH, Lin MY, Kimchi A, Chien CT, Chen RH  (2011-09)  CELL DEATH AND DIFFERENTIATION  18(9), 1507-1520  "DAPK activates MARK1/2 to regulate microtubule assembly, neuronal differentiation, and tau toxicity."
    
27. Tang HW, (Chen GC)  (2011-07)  Autophagy  7(7), 778-779  "Unraveling the role of myosin in forming autophagosomes."
    
28. Tang HW, Wang YB, Wang SL, Wu MH, Lin SY, (Chen GC)  (2011-02)  EMBO JOURNAL  30(4), 636-651  "Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy."
    
29. Ku HY, Wu CL, Rabinow L, Chen GC*, Meng TC*.  (2009)  MOLECULAR AND CELLULAR BIOLOGY  29(13), 3623-3632  "Organization of F-actin via concerted regulation of Kette by PTP61F and dAbl."
    
30. M. S. Yeh, C. H. Cheng, C. M. Chou, Y. L. Hsu, C. Y. Chu, G. D. Chen, S. T. Chen, G. C. Chen and C. J. Huang  (2008)  Dev Comp Immunol  32 (7), 814-824  "Expression and characterization of two STAT isoforms from Sf9 cells"
    
31. G. C. Chen, J. Y. Lee, H. W. Tang, J. Debnath, S. M. Thomas and J. Settleman  (2008)  Autophagy  4(1), 37-45  "Genetic interactions between Drosophila melanogaster Atg1 and paxillin reveal a role for paxillin in autophagosome formation"
    
32. V Verdier, JE Johndrow, M Betson, GC Chen, DA Hughes, SM Parkhurst and J Settleman  (2006)  Dev Biol  297, 417-432  "Drosophila Rho-kinase (DRok) is required for tissue morphogenesis in diverse compartments of the egg chamber during oogenesis"
    
33. V Verdier, GC Chen and J Settleman  (2006)  BMC Dev Biol  6, 38  "Rho-kinase regulates tissue morphogenesis via non-muscle myosin and LIM-kinase during Drosophila development"
    
34. W Jiang, R Sordella, GC Chen, S Hakre, A Roy and J Settleman  (2005)  Mol. Cell  17, 23-35  "An FF domain-dependent protein interactions mediate a signaling pathway for growth factor-induced gene expression"
    
35. GC Chen, B Turano, PJ Reust, M Hagel, J Settleman and Thomas SM  (2005)  Mol. Cell. Biol  25, 979-987  "Regulation of Rho and Rac signaling to the actin cytoskeleton by paxillin during Drosophila development"
    
36. GC Chen, P Gajowniczek and J Settleman  (2004)  Curr. Biol  14, 309-313  "Rho-LIM kinase signaling regulates ecdysone-induced gene expression and morphogenesis during Drosophila metamorphosis"
    
37. R. Sordella, W. Jiang, G. C. Chen, M. Curto and J. Settleman  (2003)  Cell  113, 147-158  "Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis"
    
38. B. L. Drees, B. Sundin, E. Brazeau, J. P. Caviston, G. C. Chen, W. Guo, K. G. Kozminski, M. W. Lau, J. J. Moskow, A. Tong, L. R. Schenkman, A. 3rd McKenzie, P. Brennwald, M. Longtine, E. Bi, C. Chan, P. Novick, C. Boone, J. R. Pringle, T. N. Davis, S. Fields, D. G. Drubin  (2001)  J. Cell Biol  154, 549-571  "A protein interaction map for cell polarity development"
    
39. G. C. Chen, Y. J. Kim and C. S. Chan  (1997)  Genes & Development  11, 2958-2971  "The Cdc42 GTPase-associated proteins Gic1 and Gic2 are required for polarized cell growth in Saccharomyces cerevisiae"
    
40. Drgonova J, Drgon T, Tanaka K, Kollar R, Chen GC, Ford RA, Chan CS, Takai Y, Cabib E.  (1996)  Science  272, 277-279  "Rho1p, a yeast protein at the interface between cell polarization and morphogenesis. "
    
41. G. C. Chen, L. Zheng and C. S. Chan  (1996)  Mol. Cell. Biol  16, 1376-1390  "The LIM domain-containing Dbm1 GTPase-activating protein is required for normal cellular morphogenesis in Saccharomyces cerevisiae"