Application of computational biology approaches to identify and develop biomarkers to predict preeclampsia

Summary Placental growth factor (PlGF) is a protein produced by the placenta during pregnancy that is critical to normal placental development. We know that it is reduced in pregnancies complicated by preeclampsia or fetal growth restriction. This project will focus on studying whether a signalling pathway, the JAK/STAT pathway, regulates PlGF in human placenta, and possibly identifying therapeutics that inhibit its expression/activation.

Project Details

The placenta represents the life support system of a pregnancy - supplying nutrients and oxygen and removing waste. When the placenta does not set up properly early in pregnancy, pregnancy complications such as preeclampsia or fetal growth restriction can occur. 

Preeclampsia is one of the most severe pregnancy complications, affecting 3-8% of all pregnancies and claiming the lives of many mothers and babies. Among survivors, its legacy is significant maternal and perinatal morbidity. For the mother this can include stroke and kidney damage, while the baby is more likely to be born preterm, sick and small. Moreover, preeclampsia leaves a lifelong footprint: affected women have significantly increased rates of future cardiovascular disease. Their babies are also at risk of lifelong chronic disease due to the consequences of impaired fetal growth and preterm birth. 

Fetal growth restriction refers to a fetus that fails to reach its genetically pre-determined growth potential during pregnancy. Indeed like preeclampsia, FGR infants are also more likely to be preterm sick and small and fetal growth restriction is the leading risk factor for stillbirth. 

Although both conditions present with differences clinically, the pathogenesis of both is related to the placenta, and poor placental set up during the early stages of pregnancy. Also common to both conditions is low production and expression of Placental Growth Factor (PlGF), a pro-angiogenic molecule that is critical to normal placental angiogenesis.

We have recently identified the Epidermal Growth Factor Receptor pathway as a negative regulator of PlGF; in particular we've identified the down stream JAK/STAT signalling pathway may play a role in its production and secretion. 

This project will seek to study JAK/STAT regulation of PlGF in human placental samples to better understand the regulation of PlGF.