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Hongmei WANG, Ph. D.

The main research interest of us is to study the physiological mechanisms of placentation and related complications and diseases, especially the key events including trophoblast invasion /migration and syncytialization


Co-workers: Long Yan, Yucui Shen, Xiaoyin Lv, Lina Cui, Ru zheng, Xiangxiang Jiang, Xing Huang, Jiao Ma, Meng Yang, Yawei Liu, Qiang Fan, Shanshan Guo, Peiye Yi, Yiming Wang.

• WANG Group website

 

  We are aimed at investigating the molecular mechanisms involved in placental development, particularly in the area of trophoblast differentiation including invasion and syncytialization of the trophoblast lineage and placentation-related diseases, such as fetal growth restriction (FGR) and preeclampsia. Human placental villous trophoblast cells undergo terminal differentiation and fusion to form the multinucleated syncytiotrophoblast, while the extravillous cytotrophoblast infiltrates the endomyometrium to anchor the placenta. Inadequate/excessive invasion of trophoblast or dysregulation in syncytialization results in early pregnancy loss, FGR or preeclampsia, etc. The main research interest of us is to study the physiological mechanisms of placentation and related complications and diseases, especially the key events including trophoblast invasion /migration and syncytialization. For many years, my lab has been working on key factors/pathways involved in embryo implantation and placental trophoblast differentiation, and has gained valuable information of the important functions of the ubiquitin-proteasome pathway, TGF-β signaling pathway, proprotein convertases and corticosteroid binding globulin (CBG) in embryo implantation, placentation and pregnancy maintenance. By combining placenta-specific knockout, knockdown/overexpression in mice, gene nucleotide polymorphism analysis and cutting-edge molecular methods, we are continuing to uncover novel mechanisms involving the aforementioned factors and pathways in placentation, with a particular focus on the following topics: (1) How is the placental syncytiotrophoblast formed? By using BeWo cell line, spontaneous syncytialization of primary human term cytotrophoblasts cells and the trophoblast explant denudation models, as well as iTRAQ, live image tracing and other well established strategies in the lab, we are trying to explore new fusogens or important factors for syncytialization, at the same time, trace the process of syncytialization (dynamic changes in membranes, cytoskeletons and organelles). Eventually, we hope to draw an experimental evidence-based model for human trophoblast syncytialization. (2) How are CTBs differentiated into the invasive phenotype? We set up an EMT model and an MET model by overexpressing CUL7, a scalfold protein of an E3 ligase, in JEG-3 cells or silencing it in HTR8/SVneo cells respectively and examined the changes in protein profiles during the morphological changes of these cells. At the same time, we pull-down and mac spec the proteins by using the F-box protein of this CUL7 E3 ligase complex. Four proteins were selected which might be brand new inducers of the morphological changes of trophoblast cells and candidate CUL7 substrates. Detailed roles and mechanisms of these molecules in trophoblast invasion and migration are being explored in the lab



Comparative anatomy of the human and mouse placental syncytiotrophoblasts and the localization of syncytins. (Aguilar PS, et al. Trends Genet, 2013).



Furin is required for syncytiotrophoblast formation. (Zhou Z, et al. Cell Death Dis, 2013)



Silencing of CUL1 suppresses trophoblast outgrowth in human placental extravillous explant cultures. (Zhang Q, et al. Cell Death Dis, 2013)

 

 

Plain english:
  We are aimed at investigating the molecular mechanisms involved in placental development, particularly in the area of trophoblast differentiation including invasion and syncytialization of the trophoblast lineage and placentation-related diseases, such as fetal growth restriction (FGR) and preeclampsia. Human placental villous trophoblast cells undergo terminal differentiation and fusion to form the multinucleated syncytiotrophoblast, while the extravillous cytotrophoblast infiltrates the endomyometrium to anchor the placenta. Inadequate/excessive invasion of trophoblast or dysregulation in syncytialization results in early pregnancy loss, FGR or preeclampsia, etc. The main research interest of us is to study the physiological mechanisms of placentation and related complications and diseases, especially the key events including trophoblast invasion/migration and syncytialization. For many years, my lab has been working on key factors/pathways involved in embryo implantation and placental trophoblast differentiation, and has gained valuable information of the important functions of the ubiquitin-proteasome pathway, TGF-β signaling pathway, proprotein convertases and corticosteroid binding globulin (CBG) in embryo implantation, placentation and pregnancy maintenance.

 

Selected publications:

  1. Lu X#, Wang Y#, Yan L, Wang L, Li W, Wang H*. Variations in mesenchymal-epithelial transition-related transcription factors during reprogramming of somatic cells from different germ layers into iPSCs. J Genet Genomics. 2016 (Accepted)
  2. Lei JH#, Yang XK#, Peng S#, Li Y, Underhill C, Zhu C, Lin HY*, Wang H*, Hammond GL*. Impact of corticosteroid-binding globulin deficiency on pregnancy and neonatal sex. J ClinEndocrinolMetab. 100(5): 1819-1827, 2015
  3. Wang R#, Dang YL#, Zheng R, Li Y, Li WW, Lu XY, Wang LJ, Zhu C, Lin HY*, Wang H*. Live cell imaging of in vitro human trophoblast syncytialization. BiolReprod. 90(6): 117,1-10, 2014 (cover story)
  4. Aguilar PS#, Baylies MK#, Fleissner A#, Helming L#, Inoue N#, Podbilewicz B*, Wang H#, Wong M#. Genetic basis of cell–cell fusion mechanisms. Trends Genet. 29(7): 427-437, 2013 (#, equal contribution.) (invited review)
  5. Zhou Z, Zhang Q, Lu XY, Wang R, Wang H, Wang YL, Zhu C, Lin HY*, Wang H*. The proprotein convertase furin is required for trophoblast syncytialization. Cell Death Dis. 4, e593, 2013

 



Four CBG variants, A51V, E102G, R64Q and R64W, were found in Han Chinese. Heterozygous CBG A51V carriers occur at a high frequency of 1:37 in Han Chinese. The production/secretion of CBG A51V is severely impaired. Plasma CBG levels in individuals heterozygous for this variant are ~50% lower than normal. (Lin HY, et al. J Clin Endocrinol Metab, 2012)



Over-expression of ubiquitin ligase Cullin7 in choriocarcinoma cell line JEG3 induced cell morphological changes characteristic of epithelial-mesenchymal transition (EMT). (Fu JJ, et al. J Biol Chem, 2010)