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Our team works in three areas. First, we are investigating the mechanism by which human placental trophoblast cells invade the uterus during normal pregnancy. The development of the human fetus depends on the ability of the embryo to rapidly enter the maternal circulation. Cytotrophoblasts, which form the fetal part of the human placenta, solve this problem by transiently exhibiting certain invasive tumor-like properties. Our study shows that both in vivo and in vitro cytotrophoblast invasion is accompanied by dramatic shifts in the expression of cell matrix-degrading metalloproteinases and adhesion molecules in normal pregnancy. Functional perturbation experiments demonstrate that cytotrophoblasts carefully regulate their invasive potential by simultaneously expressing many molecules that promote or inhibit invasion. Furthermore, we found that cytotrophoblasts, which replace the endothelial lining of uterine blood vessels, also have a surprising ability to mimic the vascular cell adhesion phenotype. This phenomenon is likely a key component of a normal placenta. What controls this highly unusual differentiation process? Since cytotrophoblasts target large-caliber arterioles for invasion, we reasoned that oxygen tension might play a role. Recently, we found that oxygen controls whether cells proliferate or exit the cell cycle and differentiate. Eph/ephrin family members, transmembrane ligands and receptors, mode invasion in arterial bias. Finally, we used molecular information on cytotrophoblast function in normal pregnancy to look for defects associated with pregnancy complications, such as preeclampsia (eg, dangerously high blood pressure). For example, our work shows that this pregnancy complication is characterized by specific abnormalities in the trophoblast secretion of angiogenic/angiogenic substances.
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Cheng Wang,Yan Zhou,Yuejun Wang,Tuhin Kumar Guha, Zhida Luo,Tara I McIntyre,Marisa E Schwab,Brittany R Davidson,Gabriella C Reeder,Ronald J Wong, Sarah England,Juan M Gonzalez,
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Toxicological sciences : an official journal of the Society of Toxicologyno. 2 (2023): 187-199
Nida Ozarslan,Joshua F. Robinson,Sirirak Buarpung,M. Yvonne Kim, Megan R. Ansbro,Jason Akram,Dennis J. Montoya,Moses R. Kamya, Abel Kakuru,Grant Dorsey,Philip J. Rosenthal,Genhong Cheng,
biorxiv(2023)
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Chesley's Hypertensive Disorders in Pregnancypp.117-129, (2022)
Bhavisha Bakrania,Ira M. Bernstein,Graham J. Burton,Tereza Cindrová‐Davies,Marilyn J. Cipolla,Kirk P. Conrad, Sandra T. Davidge, Christianne de Groot,Ralf Dechend, Ernesto Antônio Figueiró-Filho,Susan J. Fisher,Eric M. George,
Elsevier eBookspp.vii-ix, (2022)
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