During pregnancy, the uterine vasculature undergoes remarkable levels of growth and remodeling compared to other blood vessels in adults, characterized by a more than two-fold increase in blood vessel diameter and a three to five-fold increase in vessel length, as the uterus expands to contain the developing fetus. The changes in the vessels allow a ten-fold increase in placental blood flow by the time of birth. Impairment in these growth and remodeling mechanisms results in insufficient blood flow which can cause the conditions preeclampsia and growth restriction. Preeclampsis is the second leading cause of maternal mortality in the US and intrauterine growth restriction is the largest contributing factor to still births. Despite decades of medical research, the underlying mechanisms remain poorly understood. This research will take a novel engineering approach to the problem by creating a computer model of vascular remodeling that will work first for the mouse and then be adapted for humans. The research project will engage with high school and college students who have a passion for using science, technology, engineering, and mathematics (STEM) to address health disparities.
The research objective of this project is to characterize the growth and remodeling of the uterine vasculature in pregnancy and preeclampsia. Preeclampsia exclusively affects humans; however, the majority of animal studies of preeclampsia have been performed in rats and mice. To meet this research objective, computational models that combine solid mechanics, fluid mechanics, and growth and remodeling of the uterine vasculature during pregnancy, both in mice and in humans, will be developed. Parametric studies will be performed to quantify the consequences of competing hypotheses regarding the development and progression of preeclampsia. Experimental studies, using mouse models of preeclampsia, will be performed to test and validate the computational modeling results. The education objective of this project is to foster the process of training students to translate STEM rigor into innovative solutions to grand challenges in global health, like preeclampsia, that are important, both to the student and to our world. Global TECH STEM modules will be developed to expose middle & high school students, with emphasis on female students and under-represented minorities, to STEM innovations that have changed the developing world. High school, undergraduate, and graduate students will be mentored to conduct independent, innovative, and globally-minded research, including international research experience.