Dr. Guller's Lab
Research in Dr. Guller’s laboratory focuses on placental dysfunction in adverse preterm pregnancy outcomes including preeclampsia (PE), intrauterine growth restriction, and chorioamnionitis (CAM). The overall goal of his work is to elucidate the role of major cell types of the placental villus, including syncytiotrophoblast, Hofbauer cells (HBCs, fetal macrophages), fibroblasts, and fetal endothelial cells, in mediating responses to glucocorticoid, hypoxia-reperfusion injury, and intrauterine infection.
1. Role of Hofbauer Cells in Adverse Pregnancy Outcomes: Our previous studies indicate that HBC phenotype and function provide key insight into placental pathophysiology in CAM and PE. CAM was found to be associated with a focal increase in the numbers of HBCs in the placental villus, whereas PE was associated with a reduction in HBC numbers. In addition, our recent report demonstrated that glucocorticoid treatment of HBCs in vitro, as well as maternal administration of glucococorticoid, has a profound effect on HBC gene expression and function. Ongoing studies will determine the role of HBCs in infection- as well as hypoxia/reperfusion injury-driven placental damage. We will first identify aberrant patterns of HBC gene/protein expression and function in placentas from pregnancies with PE and CAM, and then use primary cultures of HBCs and macrophage cell lines to establish molecular mechanisms resulting in placental dysfunction. The importance of cell:cell communication in the placental villus will be determined using co-culture experiments with major placental cell types. These studies will provide new markers and insight into the mechanism of placental dysfunction in major adverse obstetrical outcomes.
2. Role of Placental Factors in Maternal Endothelial Dysfunction in Preeclampsia: We recently demonstrated that the system of dual (maternal+fetal) placental perfusion affords a unique opportunity to study the role of placental factors associated with elevated maternal blood pressure and proteinuria in PE (e.g. syncytiotrophoblast microparticles, sFlt-1, endoglin, plasminogen activator inhibitors). In current studies we are dissecting the specific contributions of factors released by the placenta during perfusion– including microparticles, cytokines, and chemokines– on endothelial inflammation, activation and function. These studies will lead to interventions which reduce the severity of maternal symptoms associated with PE and reduce the incidence of iatrogenic preterm delivery.