Identification of Molecular Subclasses of Preeclampsia

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Preeclampsia (PE) is a life-threatening disorder of pregnancy, characterized by new onset hypertension and multi-organ dysfunction. This disorder affects 3-5% of all pregnancies and is responsible for over 63,000 maternal deaths worldwide per year. PE has no cure short of removal of the causative organ, the placenta, which in some cases necessitates the preterm delivery of the baby. Despite years of research into the underlying cause of PE, we have yet to discover effective screening tools and/or treatments for this disorder. Landmark findings have shed light on potential biomarkers or therapeutic targets for this disorder, however the crucial finding in all human studies to date is that no one factor is common to all women diagnosed with PE. We hypothesize that PE is a spectral disorder which encompasses several subclasses of placenta dysfunction driven by different molecular pathways.

In collaboration with Dr. Brian Cox at the University of Toronto, we have used a systems biology approach to identify distinct subclasses of PE. Molecular profiling of placental tissue from over 300 patients who span the clinical spectrum of PE has successfully identify 3 distinct types of PE with different underlying pathophysiology. Our results have demonstrated that PE is the result of: 1) maternal maladaptation to pregnancy; 2) insufficient utero-placental blood flow; or, 3) excessive immune activation at the maternal-fetal interface (PMID: 25679511, 27160201). We are currently in the process of validating identified biomarkers for each PE subclass and developing these biomarkers in clinically relevant tools for the early prediction and/or diagnosis of PE. Future endeavors with this project will be focused the development of subclass-specific therapeutic interventions for PE.