專任研究人員
hwchen@gate.sinica.edu.tw +886-2-27855696,6090
陳宏文 研究員
中研院生化所 609室
研究領域與專長
學經歷
主要著作
著作列表

研究領域與專長

本實驗室的研究目標在探討成體幹細胞維持幹性（stemness）及進行分化(differentiation)的分子機制。人類胎盤為絨毛組織(villi)所構成，組織中的滋養幹細胞(trophoblast stem cells, TS cells)可分化為多核的合體滋養細胞(multinucleate syncytiotrophoblasts, STBs)及移行的外絨毛滋養細胞(migratory extravillous trophoblasts, EVTs)。另外，絨毛組織中的細胞滋養細胞(cytotrophoblasts, CTBs)具有類似TS細胞的特性。GCM1轉錄因子主宰STB 及EVT的分化，其活性受到不同訊息傳遞路徑的正、反向控制。藉由調整這些路徑，我們成功地將CTBs轉分化為TS細胞。胎盤負責母親與胎兒之間養分及氣體的交換。功能不健全的胎盤導致子癇前兆(preeclampsia, PE)及子宮內生長遲緩(intrauterine growth retardation, IUGR)等症狀，使胎兒在懷孕過程中處於營養不良的狀況，將來在成人階段也會有冠狀動脈、高血壓、中風及第二型糖尿病的高好發機率。我們當前利用TS細胞研究（1）維持其幹性的上游調控因子，（2）進一步誘導其為多能性的幹細胞以提供自體細胞療法及（3）研究TS細胞分化缺陷與PE及IUGR成因的關連性。

學經歷

  • 1994   博士, 美國佛羅里達大學
  • 1986   學士, 動物學系, 國立臺灣大學
  • 2008 – 迄今   研究員, 中研院生化所
  • 2003 – 2008   副研究員, 中研院生化所
  • 1996 – 2003   助研究員, 中研究生化所
  • 1994 – 1996   Visiting Fellow , 美國國家衛生研究院
  • 1991 – 1994   Adjunct Scientist, 美國國家衛生研究院

主要著作

A novel cAMP/Epac1/CaMKI signaling cascade promotes GCM1 desumoylation and placental cell fusion.  
Chang, C.W.; Chang, G.D.; Chen, H.  
Mol. Cell. Biol. (2011)

Dual-specificity phosphatase 23 mediates GCM1 dephosphorylation and activation.  
Lin, F.Y.; Chang, C.W.; Cheong, M.L.; Chen, H.C.; Lee, D.Y.; Chang, G.D.; Chen, H.  
Nucleic Acids Res. (2011)

GCM1 Regulation of the Expression of Syncytin-2 and Its Cognate Receptor MFSD2A in Placenta.  
Liang, C.Y.; Wang, L.J.; Chen, C.P.; Chen, L.F.; Chen, Y.H.; Chen, H.  
Biol. Reprod. (2010)

Gcm Protein Degradation Suppresses Proliferation of Glial Progenitors.  
Ho, M.; Chen, H.; Chen, M.; Jacques, C.; Giangrande, A.; and Chien, C.T.  
Proc. Natl. Acad. Sci. USA (2009)

Mechanism of Hypoxia-Induced GCM1 Degradation: Implications for the Pathogenesis of Preeclampsia.  
Chiang MH, Liang FY, Chen CP, Chang CW, Cheong ML, Wang LJ, Liang CY, Lin FY, Chou CC, Chen H 
J. Biol. Chem. (2009)

Functional Characterization of the Human Placental Fusogenic Membrane Protein Syncytin 2.  
Chen, C.P.; Chen, L.F.; Yang, S.R.; Chen, C.Y.; Ko, C.C.; Chang, G.D.; Chen, H.  
Biol. Reprod. (2008)

Ubiquitin-Conjugating Enzyme UBE2D2 Is Responsible for F-Box and WD Repeat Domain Containing 2-Mediated Human Glial Cell Missing Homolog 1 Ubiquitination and Degradation.  
Chiang, M.H.; Chen, L.F.; Chen, H.  
Biol. Reprod. (2008)

Small Ubiquitin-like Modifier Modification Regulates the DNA Binding Activity of Glial Cell Missing Drosophila Homolog a.  
Chou, C.C.; Chang, C.W.; Liu J.H.; Hsiao, C.D.; Chen, H.  
J. Biol. Chem. (2007)

Thiazolidinediones modulate the expression of beta-catenin and other cell-cycle regulatoryproteins by targeting the F-box proteins of Skp1-Cul1-F-box protein E3 ubiquitin ligase independently of peroxisome proliferator-activated receptor gamma.  
Wei, S.; Lin, L.F.; Yang, C.C.; Wang, Y.C.; Chang, G.D.; Chen, H.; Chen, C.S.  
Mol. Pharm. (2007)

Histone Deacetylase 3 Binds to and Regulates the GCMa Transcription Factor.  
Chuang, H.C.; Chang, C.W.; Chang, G.D.; Yao, T.P.; Chen, H.  
Nucleic Acids Res. (2006)

著作列表

  1. Wang LJ, Chen CP, Lee YS, Ng PS, Chang GD, Pao YH, Lo HF, Peng CH, Cheong ML, (Chen H)*  (2022-03)  Nat Commun  13, 1626  "Functional Antagonism between ΔNp63alpha and GCM1 Regulates Human Trophoblast Stemness and Differentiation"
  2. Wang LJ, Lo HF, Lin CF, Ng PS, Wu YH, Lee YS, Cheong ML, and (Chen H)*  (2019-01)  FASEB J  33, 314-326  "SFRP3 Negatively Regulates Placental Extravillous Trophoblast Cell Migration Mediated by the GCM1-WNT10B-FZD7 Axis"
  3. Chiu YH, Yang MR, Wang LJ, Chen MH, Chang GD, (Chen H)*  (2018-06)  J Biol Chem  293, 9801-9811  "New Insights into the Regulation of Placental Growth Factor Gene Expression by the Transcription Factors GCM1 and DLX3 in Human Placenta"
  4. Lo, HF, Tsai, CY, Chen, CP, Wang, LJ, Lee, YS, Chen, CY, Liang, CT, Cheong, ML, (Chen, H)*  (2017-02)  J Pathol  241, 324-336  "Association of Dysfunctional Synapse Defective 1 (SYDE1) with Restricted Fetal Growth – SYDE1 Regulates Placental Cell Migration and Invasion"
  5. Chiu, YH and (Chen, H)*  (2016-02)  Sci Rep  6, 21630  "GATA3 Inhibits GCM1 Activity and Trophoblast Cell Invasion"
  6. Cheong ML, Wang LJ, Chuang PY, Chang CW, Lee YS, Lo HF, Tsai MS, (Chen H)*  (2016-01)  Mol Cell Biol  36, 197-209  "A Positive Feedback Loop between Glial Cells Missing 1 (GCM1) and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGbeta Expression and Cell Differentiation"
  7. Chen, YY, Chuang, PY, Chen, CP, Chiu, YH, Lo, HF, Cheong, ML, Huang, JY, Kuo, PL, and (Chen, H)*  (2014)  J Biol Chem  289, 22958-22968  "Functional Antagonism between High-temperature Requirement Protein A (HtrA) Family Members Regulates Trophoblast Invasion"
  8. Chang, CW, Cheong, ML, Chang, GD, Tsai, MS, and (Chen, H)*  (2013-11)  Mol Hum Reprod  19, 745-755  "Involvement of Epac1/Rap1/CaMKI/HDAC5 Signaling Cascade in the Regulation of Placental Cell Fusion"
  9. Wu, YH, Lo, HF, Chen, SH, and (Chen, H)*  (2013-07)  FASEB J  27, 2818-2828  "Caspase-14 Suppresses GCM1 Acetylation and Inhibits Placental Cell Differentiation"
  10. Wang, CC, Lo, HF, Lin, SY, and (Chen, H)*  (2013)  Biochem J  453, 201-208  "RACK1 (Receptor for Activated C-kinase 1) Interacts with FBW2 (F-box and WD-repeat domain-containing 2) to Up-regulate GCM1 (Glial Cell Missing 1) Stability and Placental Cell Migration and Invasion"
  11. Wang, LJ, Cheong, ML, Lee, YS, Lee, MT, and (Chen, H)*  (2012-09)  Mol Cell Biol  32, 3707-3717  "High-temperature Requirement A4 (HtrA4) Suppresses the Fusogenic Activity of Syncytin-1 and Promotes Trophoblast Invasion"
  12. Chang, CW, Chang, GD, and (Chen, H) *  (2011-09)  Mol Cell Biol  31, 3820-3831  "A Novel cAMP/Epac1/CaMKI Signaling Cascade Promotes GCM1 Desumoylation and Placental Cell Fusion"
  13. Lin, FY, Chang, CW, Cheong, ML, Chen, HC, Lee, DY, Chang, GD, and (Chen, H)*  (2011-02)  Nucleic Acids Res  39, 848-861  "Dual-specificity Phosphatase 23 Mediates GCM1 Dephosphorylation and Activation"
  14. Liang, CY, Wang, LJ, Chen, CP, Chen, LF, Chen, YH, and (Chen, H)*  (2010)  Biol Reprod  83, 387-395  "GCM1 Regulation of the Expression of Syncytin 2 and Its Cognate Receptor MFSD2A in Human Placenta"
  15. Ho MS, (Chen H), Chen M, Jacques C, Giangrande A, Chien CT  (2009)  Proceedings of the National Academy of Sciences of the United States of America  106(16), 6778-6783  "Gcm Protein Degradation Suppresses Proliferation of Glial Progenitors"
  16. Chiang MH, Liang FY, Chen CP, Chang CW, Cheong ML, Wang LJ, Liang CY, Lin FY, Chou CC, (Chen H)  (2009)  J Biol Chem  284(26), 17411-17419  "Mechanism of Hypoxia-Induced GCM1 Degradation: Implications for the Pathogenesis of Preeclampsia"
  17. C. P. Chen, L. F. Chen, S. R. Yang, C. Y. Chen, C. C. Ko, G. D. Chang and H. Chen  (2008)  Biol Reprod  79, 815-823  "Functional Characterization of the Human Placental Fusogenic Membrane Protein Syncytin 2"
  18. M. H. Chiang, L. F. Chen and H. Chen  (2008)  Biol Reprod  79, 914-920  "Ubiquitin-Conjugating Enzyme UBE2D2 Is Responsible for F-Box and WD Repeat Domain Containing 2-Mediated Human Glial Cell Missing Homolog 1 Ubiquitination and Degradation"
  19. C. C. Chou, C. W. Chang, J. H. Liu, C. D. Hsiao and H. Chen  (2007)  J Biol Chem  282, 27239-27249  "Small Ubiquitin-like Modifier Modification Regulates the DNA Binding Activity of Glial Cell Missing Drosophila Homolog a"
  20. S. Wei, L. F. Lin, C. C. Yang, Y. C. Wang, G. D. Chang, H. Chen and C. S. Chen  (2007)  Molecular Pharmaceutics  72, 725-733  "Thiazolidinediones modulate the expression of beta-catenin and other cell-cycle regulatoryproteins by targeting the F-box proteins of Skp1-Cul1-F-box protein E3 ubiquitin ligase independently of peroxisome proliferator-activated receptor gamma."
  21. C. P. Chen, K. G. Wang, C. Y. Chen, C. Yu, H. C. Chuang and (H. Chen)  (2006)  BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY  113, 152-158  "Altered Placental Syncytin and Its Receptor ASCT2 Expression in Placental Development and Pre-eclampsia"
  22. H. C. Chuang, C. W. Chang, G. D. Chang, T. P. Yao and H. Chen  (2006)  Nucleic Acids Res  35, 1459-1469  "Histone Deacetylase 3 Binds to and Regulates the GCMa Transcription Factor"
  23. C. Lin, M. Lin and H. Chen  (2005)  Biochem Cell Biol  83, 188-195  "Biochemical Characterization of the Human Placental Transcription Factor GCMa/1"
  24. C. S. Yang, C. Yu, H. C. Chuang, C. W. Chang, G. D. Chang, T. P. Yao and H. Chen  (2005)  J Biol Chem  280, 10083-10090  "FBW2 Targets GCMa to the Ubiquitin-Proteasome Degradation System"
  25. C. W. Chang, H. C. Chuang, C. Yu, T. P. Yao and H. Chen  (2005)  Mol Cell Biol  25, 8401-8414  "Stimulation of GCMa Transcriptional Activity by Cyclic AMP/Protein Kinase A Signaling Is Attributed to CBP-Mediated Acetylation of GCMa"
  26. C. P. Chen, C. Y. Chen, Y. C. Yang, T. H. Su and H. Chen  (2004)  Placenta  25, 413-421  "Decreased placental GCM1 (glial cells missing) gene expression in pre-eclampsia"
  27. C. Chang, P. T. Chen, G. D. Chang, C. J. Huang and H. Chen  (2004)  Biol Reprod  71, 1956-1962  "Functional characterization of the placental fusogenic membrane protein syncytin"
  28. G. D. Chang, C. J. Chen, C. Y. Lin, H. C. Chen and H. Chen  (2003)  J Biotechnol  102, 61-71  "Improvement of glycosylation in insect cells with mammalian glycosyltransferases"
  29. C. Yu, K. Shen, M. Lin, P. Chen, C. Lin, G. D. Chang and H. Chen  (2002)  J Biol Chem  277, 50062-50068  "GCMa regulates the syncytin-mediated trophoblastic fusion"
  30. C. D. Wang, G. D. Chang, Y. K. Lee and H. Chen  (2001)  Biol Reprod  65, 1437-1443  "A functional composite cis-element for NF kappa b and RBJ kappa in the rat pregnancy-specific glycoprotein gene"
  31. H. Chen, G. D. Chang  (2001)  Electrophoresis  22, 1894-1899  "Simultaneous immunoblotting analysis with activity gel electrophoresis in a single polyacrylamide gel"
  32. H. Chen, Y. Chong and C. L. Liu  (2000)  Biochemistry  39, 1675-1682  "Active intracellular domain of Notch enhances transcriptional activation of CCAAT/enhancer binding protein beta on a rat pregnancy-specific glycoprotein gene"
  33. A. Zingone, H. Hiraiwa, C. J. Pan, B. Lin, H. Chen, J. M. Ward and J. Y. Chou  (2000)  J Biol Chem  275, 828-832  "Correction of glycogen storage disease type 1a in a mouse model by gene therapy"
  34. Y. Chong, H. Chen  (2000)  Biotechniques  29, 1166-1167  "Preparation of functional recombinant protein from E. coli using a nondetergent sulfobetaine"
  35. S. H. Lin, H. Cheng, K. Earley, W. Luo and J. Chou  (1998)  Biochemical and Biophysical Research Communications  245, 472-477  "Demonstration of adhesion activity of the soluble Ig-domain protein C-CAM4 by attachment to the plasma membrane"
  36. C. J. Pan, K. J. Lei, H. Chen, J. M. Ward and J. Y. Chou  (1998)  Arch Biochem Biophys  358, 17-24  "Ontogeny of the murine glucose-6-phosphatase system"
  37. K. J. Lei, H. Chen, C. J. Pan, J. M. Ward, B. Mosinger, Jr., E. J. Lee, H. Westphal, B. C. Mansfield and J. Y. Chou  (1996)  Nat Genet  13, 203-209  "Glucose-6-phosphatase dependent substrate transport in the glycogen storage disease type-1a mouse"
  38. G. Chen, C. T. Guy, H. W. Chen, N. Hu, E. Y. Lee and W. H. Lee  (1996)  J Biol Chem  271, 9567-9572  "Molecular cloning and developmental expression of mouse p130, a member of the retinoblastoma gene family"