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。
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。
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
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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"
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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"
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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"
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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"
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Chiu, YH and (Chen, H)* (2016-02) Sci Rep 6, 21630 "GATA3 Inhibits GCM1 Activity and Trophoblast Cell Invasion"
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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"
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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"
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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"
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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"
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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"
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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"
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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"
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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"
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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"
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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"
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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"
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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"
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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"
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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"
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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."
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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"
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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"
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C. Lin, M. Lin and H. Chen (2005) Biochem Cell Biol 83, 188-195 "Biochemical Characterization of the Human Placental Transcription Factor GCMa/1"
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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"
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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"
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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"
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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"
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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"
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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"
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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"
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H. Chen, G. D. Chang (2001) Electrophoresis 22, 1894-1899 "Simultaneous immunoblotting analysis with activity gel electrophoresis in a single polyacrylamide gel"
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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"
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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"
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Y. Chong, H. Chen (2000) Biotechniques 29, 1166-1167 "Preparation of functional recombinant protein from E. coli using a nondetergent sulfobetaine"
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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"
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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"
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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"
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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"