Molly McAdow

My primary research focus is mechanisms of endothelial dysfunction in preeclampsia. In particular, I am interested in the role of Plasminogen activator inhibitor (PAI)-1 and -2 in modulating endothelial cell biology and endothelial nitric oxide synthase activity in maternal vasculature and in the placenta. While alterations in circulating PAI-1 and PAI-2 in preeclampsia have been well recognized, a mechanistic role for these changes in preeclampsia has never been identified. These represent a potential novel target for therapeutic intervention in preeclampsia. To pursue this research focus, I have sought mentorship outside my primary department in order to learn new skill sets and understanding that I can bring back to my Department. I have received career development awards for this project from the Yale Center for Clinical Investigation/Yale Physician Scientist Development Program and the Society for Maternal Fetal Medicine/American Association for Obstetricians and Gynecologists Foundation. I also received an award from the Doris Duke Fund to Retain Clinical Scientsits-COVID19 to support this research. I have also received support through the McKern award in the Department of Obstetrics, Gynecology, & Reproductive Sciences. In addition to my own work in preeclampsia, I am collaborating with another physician-scientist investigator at Yale School of Medicine to explore the use of placental-derived exosomes in the diagnosis and pathophysiology of preeclampsia. I am the content expert as a Maternal Fetal Medicine provider and preeclampsia researcher; I have contributed to study design and plans for future work.

A secondary research interest is in the biology of parturition, particularly labor induction. Oxytocin is the most commonly used medication in pregnancy, but there are significant limitations to our understanding of oxytocin biology and which patients will respond to it. After prolonged exposure to oxytocin, myometrial cells lose their sensitivity to it. I am studying the process of the resensitization and the differences in pathway activation between patients who receive exogenous IV oxytocin for induction of labor versus those who use nipple stimulation, to activate their own endogenous pathways. This work has been supported by a research grant from the Perinatal Research Consortium.

The postpartum time is a sensitive window in the life of the mother and newborn, but there are critical disparities in outcomes for non-Hispanic black mothers and their infants. In particular, postpartum preeclampsia is a poorly understood disease and has worse outcomes for Black women. I am conducting work on the use of maternal-infant dyadic care models to reduce healthcare disparities. This work is conducted with colleagues from pediatrics and epidemiologists from the School of Public Health through our mutual support from the Yale Center for Clinical Investigation.