Grobman Subproject

Premature birth (deliveries <37 weeks gestation) is the leading cause of mortality before the age of 5 years and a major contributor to neurological disabilities in childhood1, yet little is known about the specific mechanisms that underlie this devastating condition. In fact, our understanding of the processes that initiate labor at term (38-42 weeks gestation) is remarkably limited and whether aberrations in these same processes underlie preterm or very preterm (<34 weeks gestation) spontaneous labor is largely unknown. We propose that understanding the basic molecular and cellular processes in maternal (uterus, cervix) and fetal (placenta) reproductive tissues throughout these gestational windows is the first essential step toward developing new therapeutics and understanding the mechanisms through which sociodemographic factors, behavior, and medical conditions in pregnancy alter risks for preterm delivery. Here, we outline a research program focusing on gene regulation to identify molecular pathways involved in human birth. Our center will integrate key aspects of vertebrate evolutionary biology, human genetics and genomics, and stem cell biology to characterize genetic programs and the cellular/molecular pathways that are key for the maintenance of normal pregnancy, and whose alterations, brought about by either genetic or environmental factors, may trigger premature birth. As the fifth TDC, we will draw on the transdisciplinary expertise and resources of the other Centers and propose hypotheses and technical innovations that complement those already in place at those sites. The unique skills, resources and prior collaborations between investigators at the University of Chicago, Northwestern University, and Duke University will allow our Center not only to fill in the remaining gaps in the March of Dimes’ “roadmap” to solve prematurity1 but also to apply the most comprehensive and cutting edge evolutionary, genomic and epigenomic tools and in vitro models to the study of preterm delivery.