Year 5/NCE

Through the generous support of this award, we have been able to establish, for the first time, disease-in-a-dish models for the common pregnancy disorder, preeclampsia. This is an extremely difficult disease to study due to its origin during early pregnancy and lack of proper animal models which can recapitulate human placental development. Using our preeclamptic iPSC lines, we have been able to find a common defect in early differentiation of placental cells, a defect which further explains the abnormal development and function of the placenta in this pregnancy complication. We have also been able to identify small molecules which at least partially reverse this phenotype, promoting differentiation of the invasive placental cells which show abnormal development and function in preeclampsia. We are currently beginning to further test these small molecules as potential therapeutics for prevention of this devastating pregnancy disorder, a feat which would not have been conceivable in the not-so-distant past. Given this success, we have also begun to expand this work into modeling other placenta-based pregnancy complications, including spontaneous preterm birth and placenta accreta. Establishment of such models will both shed light on the pathophysiology of these diseases and provide a platform for identification of diagnostic biomarkers and therapeutic targets.