Lala Lab - Research - Area 1
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Area of Research Interest 1: Mechanisms at the fetal-maternal interface regulating placental development and functions

The human placenta, an essential organ for fetal survival, is a highly invasive pseudo-tumor-like structure in which certain placental cells known as the extravillous trophoblast (EVT) invade the uterus and its arteries to derive adequate nutrients for the fetus. Poor EVT cell invasion of uterine arteries results in inadequate flow of maternal blood to the placenta, which in turn, can cause poor fetal growth (fetal growth restriction or FGR) and also a serious pregnancy-associated disorder in the mother called preeclampsia (PE). On the other hand, uncontrolled EVT cell invasion is a feature of trophoblastic tumors. Thus EVT cell invasiveness must be exquisitely regulated in situ to maintain a healthy utero-placental homeostasis. Our research has identified many molecules produced at the fetal-maternal interface which regulate EVT cell growth, migration and invasiveness in a positive or a negative manner, as well as the signaling mechanisms responsible for such regulation. Certain molecular/genetic alterations causing trophoblast hyper-invasiveness (in trophoblastic pre-cancer or cancer) or hypo-invasiveness (e.g. in preeclampsia) have also been identified. Current research focuses on the molecular mechanisms underlying the actions of decorin (DCN), an invasion-inhibitory molecule, produced by decidual cells of the pregnant uterus, where EVT cells invade. DCN was found to control trophoblast growth and invasion by binding to multiple tyrosine kinase receptors, in particular, VEGF receptor-2. We discovered that DCN overproduction by decidual cells is causally associated with PE, and that elevated levels of DCN in the maternal plasma during the second trimester is a predictive biomarker of this disease before clinical signs appear. We are conducting a larger prospective study to test this biomarker in PE and FGR. We are also exploring the role of this molecule in trophoblast differentiation from trophoblast Stem /progenitor cells, and creating a mouse model of PE by genetically induced decorin overproduction in the decidua, that can be exploited for prevention and intervention of PE.

diagram of the first trimester human placenta

(Diagram of the first trimester human placenta)

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