The research goal of my laboratory aims at unraveling the molecular mechanism underlying the stemness and differentiation of adult stem cells. Human placentas are composed of villous tissues, which harbor trophoblast stem (TS) cells capable of differentiating into multinucleate syncytiotrophoblasts (STBs) and migratory extravillous trophoblasts (EVTs). Indeed, placental cytotrophoblasts (CTBs) exhibit TS cell-like characteristics. GCM1 transcription factor is a master regulator for STB and EVT differentiation. GCM1 activity is positively and negatively regulated by cAMP and hypoxia signaling pathways, respectively. By manipulation of signaling pathways, we are able to establish trophoblast stem (TS) cells from CTBs. The placenta is the primary site of nutrient and gas exchange between mother and fetus. Placental dysfunction is associated with the pregnancy disorders preeclampsia (PE) and intrauterine growth retardation (IUGR). The undernourished fetuses due to dysfunctional placenta will have a higher risk of developing coronary heart disease, type 2 diabetes, stroke, and hypertension in their adulthood. We are currently working on (1) the upstream regulators of trophoblast stemness, (2) the induction of TS cells into multipotent stem cells for autologous cell therapy, and (3) the pathogenesis of PE and IUGR using TS cells as a model system.
The research goal of my laboratory aims at unraveling the molecular mechanism underlying the stemness and differentiation of adult stem cells. Human placentas are composed of villous tissues, which harbor trophoblast stem (TS) cells capable of differentiating into multinucleate syncytiotrophoblasts (STBs) and migratory extravillous trophoblasts (EVTs). Indeed, placental cytotrophoblasts (CTBs) exhibit TS cell-like characteristics. GCM1 transcription factor is a master regulator for STB and EVT differentiation. GCM1 activity is positively and negatively regulated by cAMP and hypoxia signaling pathways, respectively. By manipulation of signaling pathways, we are able to establish trophoblast stem (TS) cells from CTBs. The placenta is the primary site of nutrient and gas exchange between mother and fetus. Placental dysfunction is associated with the pregnancy disorders preeclampsia (PE) and intrauterine growth retardation (IUGR). The undernourished fetuses due to dysfunctional placenta will have a higher risk of developing coronary heart disease, type 2 diabetes, stroke, and hypertension in their adulthood. We are currently working on (1) the upstream regulators of trophoblast stemness, (2) the induction of TS cells into multipotent stem cells for autologous cell therapy, and (3) the pathogenesis of PE and IUGR using TS cells as a model system.
Positions Held
- 2008 – present Research Fellow, Institute of Biological Chemistry, Academia Sinica
- 2003 – 2008 Associate Research Fellow, Institute of Biological Chemistry, Academia Sinica
- 1996 – 2003 Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica.
- 1994 – 1996 Visiting Fellow , Human Genetics Branch, NICHD, NIH.
- 1991 – 1994 Adjunct Scientist, Human Genetics Branch, NICHD, NIH.
Degrees
- 1994 Ph.D., Physiology, University of Florida.
- 1986 B.S., Zoology, National Taiwan University.
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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"