研究領域與專長

本實驗室的研究目標在瞭解胎盤滋養葉細胞(trophoblast)分化的分子機制。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。完整的人類胎盤具有很多絨毛(villi)組織與母體的血液循環接觸。在絨毛組織結構中含有的兩種主要特殊細胞型：滋養葉胞層細胞 (cytotrophoblast)及滋養葉融合層細胞(syncytiotrophoblast)。滋養葉胞層細胞具有類似幹細胞(stem cell)的功能可以增生並進行 細胞融合(cell-cell fusion)而分化為多核的(multinucleate)滋養葉融合層細胞—負責調控養分與氣體的交換以及生長因子及荷爾蒙的產生。

本實驗室的研究方向及發現如下：

  1. 人類滋養葉胞層細胞之間的融合是經由syncytin 1及 syncytin 2蛋白調節促成。Syncytin蛋白專一地在滋養葉融合層細胞表現。GCMa (glial cells missing a)蛋白是一調控胎盤發育的重要轉錄因子(transcription factor)。我們的研究發現GCMa蛋白藉由控制 syncytin基因表現而調控滋養葉細胞融，且GCMa是一半生期約為90分鐘的不穩定蛋白質。

  2. 為了探討控制GCMa蛋白半生期的分子機制，我們進一步證明含有F-box的FBW2蛋白在細胞內會促進GCMa汎素化(ubiquitination)，再經由26S proteasome 進行蛋白質降解。

  3. 長久以來已知，提高細胞內cAMP的濃度會促進胎盤滋養葉細胞的融合。我們也證明活化cAMP/PKA訊息路徑(signaling pathway)可促進其下游CBP蛋白對GCMa蛋白進行乙烯化(acetylation)修飾，使GCMa蛋白免於被汎素化及降解，進而增加其穩定性及提高其轉錄活性。

  4. 蛋白質乙烯化修飾是一可逆化學反應。為了瞭解GCMa蛋白去乙烯化(deacetylation)的機制，我們也證明了HDAC3蛋白可以跟GCMa蛋白結合並進行去乙烯化反應。

  5. 在臨床上的研究，我們探討GCMa蛋白在胎盤相關疾病—子癇先兆症(pre-eclampsia)發病過程中扮演的角色。子癇先兆症發生在6-8%的姙娠婦女，造成死胎或新生兒發病及死亡。我們發現在子癇先兆症的胎盤中GCMa基因及蛋白的表現皆低於正常的胎盤。

  6. 子癇先兆症病患的胎盤發育不正常，以致胎盤細胞處於低氧狀態(hypoxia)。我們新近發現低氧狀態啟動一訊息路徑，促進GCMa蛋白的磷酸化(phosphorylation)以及與FBW2蛋白結合，使GCMa蛋白降解。 綜合我們的研究可知藉由多重的後轉譯修飾(post-translational modification)，如汎素化、磷酸化、乙烯化，可以控制細胞內的GCMa活性以維持正常的滋養葉融合層細胞的分化及正常的胎盤生理功能。本實驗室進行中的研究計劃包括探討多重訊息路徑如何整合調節GCMa蛋白修飾、胎盤幹細胞如何啟動GCMa表現促進細胞分化、以及GCMa蛋白於子癇先兆症發病機制(pathogenesis)的角色。

學經歷
經歷
  • 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
學歷
  • 1994   博士, 美國佛羅里達大學
  • 1986   學士, 動物學系, 國立臺灣大學
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.
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, Lo HF, Lin CF, Ng PS, Wu YH, Lee YS, Cheong ML, and (Chen H)*  (2019-01)  FASEB JOURNAL  33(1), 314-326  "SFRP3 Negatively Regulates Placental Extravillous Trophoblast Cell Migration Mediated by the GCM1-WNT10B-FZD7 Axis."
  2. Chiu YH, Yang MR, Wang LJ, Chen MH, Chang GD, (Chen H)*  (2018-06)  JOURNAL OF BIOLOGICAL CHEMISTRY  293(25), 9801-9811  "New Insights into the Regulation of Placental Growth Factor Gene Expression by the Transcription Factors GCM1 and DLX3 in Human Placenta."
  3. Lo, H.-F., Tsai, C.-Y., Chen, C.-P., Wang, L.-J., Lee, Y.-S., Chen, C.-Y., Liang, C.-T., Cheong, M.-L., (Chen, H.*)  (2017-02)  The Journal of pathology  241, 324-336  "Association of Dysfunctional Synapse Defective 1 (SYDE1) with Restricted Fetal Growth – SYDE1 Regulates Placental Cell Migration and Invasion"
  4. Chiu, Y. H. and (Chen, H.)  (2016-02)  Scientific Reports  6, 21630  "GATA3 Inhibits GCM1 Activity and Trophoblast Cell Invasion"
  5. 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"
  6. Chen, Y.-Y., Chuang, P.-Y., Chen, C.-P., Chiu, Y.-H., Lo, H.-F., Cheong, M.-L., Huang, J.-Y., Kuo, P.-L., and (Chen, H.*)  (2014)  J Biol Chem  289(33), 22958-22968  "Functional Antagonism between High-temperature Requirement Protein A (HtrA) Family Members Regulates Trophoblast Invasion"
  7. Chang, C.-W., Cheong, M.-L., Chang, G.-D., Tsai, M.-S., and (Chen, H.*)  (2013-11)  Mol Hum Reprod  19(11), 745-755  "Involvement of Epac1/Rap1/CaMKI/HDAC5 Signaling Cascade in the Regulation of Placental Cell Fusion"
  8. Wu, Y.-H., Lo, H.-F., Chen, S.-H., and (Chen, H.)*  (2013-07)  FASEB J  27(7), 2818-2828  "Caspase-14 Suppresses GCM1 Acetylation and Inhibits Placental Cell Differentiation"
  9. Wang, C.-C., Lo, H.-F., Lin, S.-Y., 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"
  10. Wang, L.-J., Cheong, M.-L., Lee, Y.-S., Lee, M.-T., and (Chen, H.*)  (2012-09)  Mol Cell Biol  32(18), 3707-3717  "High-temperature Requirement A4 (HtrA4) Suppresses the Fusogenic Activity of Syncytin-1 and Promotes Trophoblast Invasion"
  11. Chang, C.-W., Chang, G.-D, and (Chen, H*)   (2011-09)  Mol Cell Biol  31(18), 3820-3831  "A Novel cAMP/Epac1/CaMKI Signaling Cascade Promotes GCM1 Desumoylation and Placental Cell Fusion"
  12. Lin, F.-Y., Chang, C.-W., Cheong, M.-L., Chen, H.-C., Lee, D.-Y., Chang, G.-D., and (Chen, H*)  (2011-02)  Nucleic Acids Res  39(3), 848-861  "Dual-specificity Phosphatase 23 Mediates GCM1 Dephosphorylation and Activation"
  13. Liang, C.-Y., Wang, L.-J., Chen, C.-P., Chen, L.-F., Chen, Y.-H., and (Chen, H*)  (2010)  Biol Reprod  83(3), 387-395  "GCM1 Regulation of the Expression of Syncytin 2 and Its Cognate Receptor MFSD2A in Human Placenta"
  14. 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"
  15. 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"
  16. 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"
  17. 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"
  18. 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"
  19. 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."
  20. 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"
  21. 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"
  22. C. Lin, M. Lin and H. Chen  (2005)  Biochem Cell Biol  83, 188-195  "Biochemical Characterization of the Human Placental Transcription Factor GCMa/1"
  23. 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"
  24. 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"
  25. 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"
  26. 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"
  27. 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"
  28. 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"
  29. 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"
  30. H. Chen, G. D. Chang  (2001)  Electrophoresis  22, 1894-1899  "Simultaneous immunoblotting analysis with activity gel electrophoresis in a single polyacrylamide gel"
  31. 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"
  32. 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"
  33. Y. Chong, H. Chen  (2000)  Biotechniques  29, 1166-1167  "Preparation of functional recombinant protein from E. coli using a nondetergent sulfobetaine"
  34. 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"
  35. 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"
  36. 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"
  37. 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"

本實驗室的研究目標在瞭解胎盤滋養葉細胞(trophoblast)分化的分子機制。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。完整的人類胎盤具有很多絨毛(villi)組織與母體的血液循環接觸。在絨毛組織結構中含有的兩種主要特殊細胞型：滋養葉胞層細胞 (cytotrophoblast)及滋養葉融合層細胞(syncytiotrophoblast)。滋養葉胞層細胞具有類似幹細胞(stem cell)的功能可以增生並進行 細胞融合(cell-cell fusion)而分化為多核的(multinucleate)滋養葉融合層細胞—負責調控養分與氣體的交換以及生長因子及荷爾蒙的產生。

本實驗室的研究方向及發現如下：

  1. 人類滋養葉胞層細胞之間的融合是經由syncytin 1及 syncytin 2蛋白調節促成。Syncytin蛋白專一地在滋養葉融合層細胞表現。GCMa (glial cells missing a)蛋白是一調控胎盤發育的重要轉錄因子(transcription factor)。我們的研究發現GCMa蛋白藉由控制 syncytin基因表現而調控滋養葉細胞融，且GCMa是一半生期約為90分鐘的不穩定蛋白質。

  2. 為了探討控制GCMa蛋白半生期的分子機制，我們進一步證明含有F-box的FBW2蛋白在細胞內會促進GCMa汎素化(ubiquitination)，再經由26S proteasome 進行蛋白質降解。

  3. 長久以來已知，提高細胞內cAMP的濃度會促進胎盤滋養葉細胞的融合。我們也證明活化cAMP/PKA訊息路徑(signaling pathway)可促進其下游CBP蛋白對GCMa蛋白進行乙烯化(acetylation)修飾，使GCMa蛋白免於被汎素化及降解，進而增加其穩定性及提高其轉錄活性。

  4. 蛋白質乙烯化修飾是一可逆化學反應。為了瞭解GCMa蛋白去乙烯化(deacetylation)的機制，我們也證明了HDAC3蛋白可以跟GCMa蛋白結合並進行去乙烯化反應。

  5. 在臨床上的研究，我們探討GCMa蛋白在胎盤相關疾病—子癇先兆症(pre-eclampsia)發病過程中扮演的角色。子癇先兆症發生在6-8%的姙娠婦女，造成死胎或新生兒發病及死亡。我們發現在子癇先兆症的胎盤中GCMa基因及蛋白的表現皆低於正常的胎盤。

  6. 子癇先兆症病患的胎盤發育不正常，以致胎盤細胞處於低氧狀態(hypoxia)。我們新近發現低氧狀態啟動一訊息路徑，促進GCMa蛋白的磷酸化(phosphorylation)以及與FBW2蛋白結合，使GCMa蛋白降解。 綜合我們的研究可知藉由多重的後轉譯修飾(post-translational modification)，如汎素化、磷酸化、乙烯化，可以控制細胞內的GCMa活性以維持正常的滋養葉融合層細胞的分化及正常的胎盤生理功能。本實驗室進行中的研究計劃包括探討多重訊息路徑如何整合調節GCMa蛋白修飾、胎盤幹細胞如何啟動GCMa表現促進細胞分化、以及GCMa蛋白於子癇先兆症發病機制(pathogenesis)的角色。

經歷
  • 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
學歷
  • 1994   博士, 美國佛羅里達大學
  • 1986   學士, 動物學系, 國立臺灣大學
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.
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)
  1. Wang LJ, Lo HF, Lin CF, Ng PS, Wu YH, Lee YS, Cheong ML, and (Chen H)*  (2019-01)  FASEB JOURNAL  33(1), 314-326  "SFRP3 Negatively Regulates Placental Extravillous Trophoblast Cell Migration Mediated by the GCM1-WNT10B-FZD7 Axis."
  2. Chiu YH, Yang MR, Wang LJ, Chen MH, Chang GD, (Chen H)*  (2018-06)  JOURNAL OF BIOLOGICAL CHEMISTRY  293(25), 9801-9811  "New Insights into the Regulation of Placental Growth Factor Gene Expression by the Transcription Factors GCM1 and DLX3 in Human Placenta."
  3. Lo, H.-F., Tsai, C.-Y., Chen, C.-P., Wang, L.-J., Lee, Y.-S., Chen, C.-Y., Liang, C.-T., Cheong, M.-L., (Chen, H.*)  (2017-02)  The Journal of pathology  241, 324-336  "Association of Dysfunctional Synapse Defective 1 (SYDE1) with Restricted Fetal Growth – SYDE1 Regulates Placental Cell Migration and Invasion"
  4. Chiu, Y. H. and (Chen, H.)  (2016-02)  Scientific Reports  6, 21630  "GATA3 Inhibits GCM1 Activity and Trophoblast Cell Invasion"
  5. 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"
  6. Chen, Y.-Y., Chuang, P.-Y., Chen, C.-P., Chiu, Y.-H., Lo, H.-F., Cheong, M.-L., Huang, J.-Y., Kuo, P.-L., and (Chen, H.*)  (2014)  J Biol Chem  289(33), 22958-22968  "Functional Antagonism between High-temperature Requirement Protein A (HtrA) Family Members Regulates Trophoblast Invasion"
  7. Chang, C.-W., Cheong, M.-L., Chang, G.-D., Tsai, M.-S., and (Chen, H.*)  (2013-11)  Mol Hum Reprod  19(11), 745-755  "Involvement of Epac1/Rap1/CaMKI/HDAC5 Signaling Cascade in the Regulation of Placental Cell Fusion"
  8. Wu, Y.-H., Lo, H.-F., Chen, S.-H., and (Chen, H.)*  (2013-07)  FASEB J  27(7), 2818-2828  "Caspase-14 Suppresses GCM1 Acetylation and Inhibits Placental Cell Differentiation"
  9. Wang, C.-C., Lo, H.-F., Lin, S.-Y., 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"
  10. Wang, L.-J., Cheong, M.-L., Lee, Y.-S., Lee, M.-T., and (Chen, H.*)  (2012-09)  Mol Cell Biol  32(18), 3707-3717  "High-temperature Requirement A4 (HtrA4) Suppresses the Fusogenic Activity of Syncytin-1 and Promotes Trophoblast Invasion"
  11. Chang, C.-W., Chang, G.-D, and (Chen, H*)   (2011-09)  Mol Cell Biol  31(18), 3820-3831  "A Novel cAMP/Epac1/CaMKI Signaling Cascade Promotes GCM1 Desumoylation and Placental Cell Fusion"
  12. Lin, F.-Y., Chang, C.-W., Cheong, M.-L., Chen, H.-C., Lee, D.-Y., Chang, G.-D., and (Chen, H*)  (2011-02)  Nucleic Acids Res  39(3), 848-861  "Dual-specificity Phosphatase 23 Mediates GCM1 Dephosphorylation and Activation"
  13. Liang, C.-Y., Wang, L.-J., Chen, C.-P., Chen, L.-F., Chen, Y.-H., and (Chen, H*)  (2010)  Biol Reprod  83(3), 387-395  "GCM1 Regulation of the Expression of Syncytin 2 and Its Cognate Receptor MFSD2A in Human Placenta"
  14. 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"
  15. 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"
  16. 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"
  17. 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"
  18. 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"
  19. 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."
  20. 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"
  21. 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"
  22. C. Lin, M. Lin and H. Chen  (2005)  Biochem Cell Biol  83, 188-195  "Biochemical Characterization of the Human Placental Transcription Factor GCMa/1"
  23. 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"
  24. 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"
  25. 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"
  26. 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"
  27. 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"
  28. 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"
  29. 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"
  30. H. Chen, G. D. Chang  (2001)  Electrophoresis  22, 1894-1899  "Simultaneous immunoblotting analysis with activity gel electrophoresis in a single polyacrylamide gel"
  31. 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"
  32. 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"
  33. Y. Chong, H. Chen  (2000)  Biotechniques  29, 1166-1167  "Preparation of functional recombinant protein from E. coli using a nondetergent sulfobetaine"
  34. 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"
  35. 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"
  36. 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"
  37. 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"