Grant: Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

Preeclampsia, a serious multi-system pregnancy complication characterized by high blood pressure after 20 weeks gestation. Preeclampsia occurs in 2-8% of pregnancies and can cause devastating short- and long-term adverse health outcomes for both the pregnant individual and child. Currently, there is no consistent method to identify pregnancies at risk of developing preeclampsia. Our long-term goal is to create an effective, non-invasive method to indicate whether a pregnancy is at-risk of developing preeclampsia. Previous studies have largely failed at developing a predictive model by not acknowledging the preeclampsia heterogeneity; it is not one disease, but rather many subtypes. This proposal aims to understand preeclampsia heterogeneity and identify novel preeclampsia subtypes based on molecular signatures. DNA methylation (DNAm), a chemical DNA modification, influences gene expression. Changes in DNAm have been observed in placentas from pregnancies with preeclampsia. DNAm has been gaining interest for use as a biomarker. However, obtaining placental samples during pregnancy is invasive and holds risk for the pregnancy. We need a non-invasive means to access placental DNA. DNA from the placenta is shed into circulation, where we can quantify it. We will use the novel cfMeDIP-seq to non-invasively enrich for placental DNA in pregnant plasma. CfMeDIP-seq allows us to obtain both DNA sequence and DNAm information. We will use DNA sequence and DNA methylation information to i) Assess tissue-specific DNAm changes in preeclampsia, and ii) Use machine learning approaches to classify and identify novel preeclampsia subtypes. This research will provide insight into preeclampsia heterogeneity and result in a classification model to classify preeclampsia cases based on molecular subtype. Future directions will involve investigating novel treatment/therapeutics options geared towards these novel molecular subtypes. This is one step closer to personalized preeclampsia treatment, and will heavily inform preeclampsia care, leading to reduced morbidity and mortality for the mother and child.