Guang-Chao Chen Lab

Functional analysis of PTPs in development and human diseases

Protein tyrosine phosphatases (PTPs) are a group of tightly regulated enzymes that coordinate with protein tyrosine kinases (PTKs) to control protein phosphorylation during cell adhesion and migration. To explore the functional role of PTPs in cell adhesion and migration, we performed genetic analyses to identify PTPs that could modulate border cell migration during Drosophila oogenesis. Depletion of Myopic (Mop), the Drosophila homolog of human HDPTP/PTPN23, resulted in aberrant integrin distribution and border cell dissociation. We further identified Rab4 GTPase as an interactor of Mop/HDPTP. HDPTP regulates Rab4 distribution, integrin trafficking, and cell motility. We also found that the FERM and PDZ domain-containing protein tyrosine phosphatase, dPtpmeg/PTPN3, negatively regulates EGFR/Ras/MAPK signaling pathway. Our recent data indicate that PTPN3 promotes EGFR degradation and inhibits lung cancer cell proliferation and migration.

Molecular signaling and PTM of autophagy

Autophagy is a process by which components of the cytoplasm (the jelly-like substance that fills a cell) are engulfed and degraded; it has recently been found to play an important role in development and in certain human diseases such as cancer, immune response, and neurodegeneration. We are applying genetic, cell biologic, and biochemical approaches to study the molecular machinery of autophagy.

Positions Held

• 2021 – present   Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2013 – present   Joint Associate Professor, Institute of Biochemical Sciences, National Taiwan University
• 2013 – 2021   Associate Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2007 – 2013   Adjunct Assistant Professor, Institute of Biochemical Sciences, National Taiwan University
• 2006 – 2012   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 1998 – 2005   Postdoctoral Fellow, MGH Cancer Center and Harvard Medical School

Degrees

• 1997   Ph.D., Molecular Genetics, University of Texas at Austin

1. 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."
   
2. 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."
   
3. 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)."
   
4. 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."
   
5. 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."
   
6. 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."
   
7. 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."
   
8. 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."
   
9. 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"
   
10. 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."
    
11. 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)."
    
12. 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."
    
13. 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"
    
14. 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"
    
15. 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."
    
16. 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."
    
17. 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"
    
18. 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."
    
19. 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"
    
20. 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."
    
21. 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."
    
22. 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."
    
23. 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."
    
24. 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."
    
25. 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."
    
26. Tang HW, (Chen GC)  (2011-07)  Autophagy  7(7), 778-779  "Unraveling the role of myosin in forming autophagosomes."
    
27. 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."
    
28. 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."
    
29. 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"
    
30. 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"
    
31. 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"
    
32. 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"
    
33. 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"
    
34. 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"
    
35. 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"
    
36. 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"
    
37. 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"
    
38. 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"
    
39. 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. "
    
40. 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"