Role of Preeclampsia Dysregulated Genes in Trophoblast Invasion and Biology

Role of Preeclampsia Dysregulated Genes in Trophoblast Invasion and Biology

The underlying pathophysiology of preeclampsia, while still not fully understood, the placenta is considered the etiologic organ and maternal endothelial dysfunction and enhanced immune response are key features.  The placental basal plate region of the placenta is a site with known preeclamptic anatomical abnormalities, characterized by shallow cytotrophoblast (CTB) invasion and limited uterine spiral artery remodeling.

Our lab has been determining the gene expression profile of this region via transcriptomics and immunohistochemistry, utilizing placentas from preeclamptic and normal placentas of various gestational ages. Ongoing projects in this lab are confirming the expression pattern of the identified molecules determining which cell types express these molecules of interest (i.e., CTBs, decidua or immune cells) in the basal plate region. The functional significance of the molecules in trophoblast biology are explored by employing functional perturbation studies using in vitro model systems. Ultimately, the results of these studies should identify key molecules and molecular pathways that potentially serve as therapeutic targets for the prevention and/or treatment of preeclampsia.

Endothelial Progenitor Cells in Pregnancy and Preeclampsia

A central feature of preeclampsia pathogenesis is maternal endothelial dysfunction.  We are interested in understanding the role of endothelial progenitor cells (EPCs) in the pathophysiology of preeclampsia. EPC dysfunction may also mediate the long-term cardiovascular health consequences associated with preeclampsia patients.  While much has been accomplished in characterizing the systemic endothelial dysfunction of preeclampsia, the role of EPCs in the mechanism is not fully understood. Moreover, study of these cells may provide potential cellular targets for novel therapies. Our lab is examining the types and alterations in EPC throughout pregnancy and in preeclampsia (i.e., during pregnancy, at delivery, and post-delivery.)

Placental Extracellular Vesicles and Impact on Maternal System

Placental Extracellular Vesicles

The syncytial lining of the placenta is in direct contact with maternal blood and sheds grams of extracellular vesicles into maternal circulation toward the end of pregnancy. These vesicles contain both surface molecules and internal cargo that can direct or alter the biology of the recipient cell they encounter. Our lab is exploring novel methods to (1) assess these vesicles in such a way that placental health can be ascertained via a blood draw and (2) understand how these “placental packages” are used to communicate and regulate maternal physiology during pregnancy. We are particularly interested in exploring their effects on the endothelium and immune system.

Assessment of Placental Health

Assessment of Placental Health

With the advancement of sequencing of cfDNA and cfRNA from blood, the opportunity to “biopsy” the placenta safely during an ongoing pregnancy using these modalities may now be possible.  In collaboration with Dr. Julie Baker and Dr. Ansul Kundaje, we are characterizing the placental signature in maternal blood. The ultimate goal is to be able to detect pregnancy placental issues earlier in pregnancy than is currently possible and develop protocols for monitoring placental health.

Winn Perinatal Biobank

The Winn Laboratory has procured placental biopsies, cord blood, maternal blood, and/or maternal urine from over 200 preeclamptic and normotensive pregnancies. Our Winn Lab Perinatal Biobank is a valuable resource that supports both basic and translational research studies to understand the remarkable process of pregnancy and the pathophysiology of preeclampsia. Our work strives to identify predictive and diagnostic biomarkers for obstetric complications and to determine potential therapeutic targets. Our goal is to improve maternal, fetal and child health.

Current Translational Studies

 The EPOCH study celebrating having enrolled over 100 people.