Small intestinal remodeling across pregnancy cycles

PROJECT SUMMARY Pregnancy represents a developmental window of profound change across virtually every tissue in the maternal body. While central roles for the uterus and mammary gland in this process are well established, we lack fundamental knowledge about the cellular changes that occur at other sites and how they affect short- and long-term maternal health. In this work, we will investigate tissue remodeling in the small intestine; an organ that must increase its nutrient uptake massively to absorb an estimated excess of 50,000 kcal throughout human pregnancy and 500 kcal per day during lactation. While gross anatomical changes of the intestine during pregnancy have been documented for decades, and reduced intestinal motility is one of the most common pregnancy symptoms, the cellular, molecular, and tissue-level mechanisms that remodel the intestine at this stage are not understood. The goal of this project is to identify unique aspects of the pregnant body that stimulate stem cells and drive intestinal remodeling to support maternal physiology. Cardiovascular disease, diabetes, and other metabolic disorders are among the leading causes of maternal morbidity and mortality during and in the year after pregnancy. We will use pregnancy as a model to study fundamental principles of tissue regeneration, while providing urgently needed insights into the poorly understood biology that underlies rising incidences of these pregnancy-associated diseases. The New Innovator Award would allow me to apply my expertise in epithelial tissue regeneration and nutrient metabolism to establish an urgently needed baseline of mechanistic understanding of the programs that remodel maternal digestive organs during pregnancy.