Mechanisms of Placenta Accreta Spectrum
Faculty Mentor’s Name: Professor Helen Jones
Phone Number: (513) 227-2869
Project Category: Translational
International Component or Travel: No
A failure in the development of the maternal-fetal interface is associated with unsuccessful pregnancies including recurrent spontaneous abortion, fetal growth restriction, pre-eclampsia, and placenta accrete spectrum. The latter is a general term used to describe the clinical condition when cells of the placenta invades beyond the decidua and fails to separate from the uterine wall. The incidence of placenta accreta has increased significantly over the last decades and is currently estimated to be 1 in ~530 births. While in part this increase may be linked to the increase in cesarean delivery rate, immunological and/or genetic factors are thought to play an important role as well. For instance, recent studies link the development of placenta accreta with significantly reduced numbers of uterine natural killer cells (uNK), while no significant association with the number of uterine scars was observed1,2. Importantly, evidence suggests that uNK cells play a critical role in the development of the decidua basalis (DB), spiral artery development and regulation of trophoblast invasion. The involvement of uNK cells is already evident at an early stage where they expand rapidly and their activation is thought to mediate de novo vasculature development, the ‘trophoblast-independent’ stage of spiral artery remodeling, and control the depth and pattern of fetal trophoblast invasion. Despite the vital roles of uNK cells in the DB and establishment of the maternal-fetal interface, the molecular mechanisms controlling their expansion, activation and function during gestation remain poorly understood. This project will examine the communication signals between uNK cells and the placental trophoblast.
Leveraging Sleep/Wake Homeostasis to Improve Physiology and Health
Faculty Mentor’s Name: Dr. Andrew Liu
Phone Number: (352) 294-8900
Project Category: Basic
Sleep/wake homeostasis is critical for physiology and health. In mammals, the sleep/wake cycle is regulated by the master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus. Circadian disruption has been associated with various sleep, metabolic and neuropsychiatric disorders. The proposed project aims to determine whether and how disruption of the SCN clock using conditional genetic perturbation in mice alters the sleep/wake homeostasis. We will focus on the mTOR nutrient-sensing and NF-kB inflammatory pathways that were shown to be clock modifiers in our recent studies. We will use the highly sensitive and non-invasive piezoelectric sleep assay system to monitor their sleep/wake states and assess sleep quantity and quality. We will consider treatment regimens that inhibit nutrient sensing and/or inflammation such as optimized light condition, time-restricted feeding, caloric restriction, and pharmacological agents. Successful completion of the project will provide the foundation for future studies of circadian/sleep integration with physiological homeostasis. The long-term goal of this research is to investigate the genetic, environmental, and pharmacological factors that impact the circadian and sleep systems. This research has broad implications in diseases and chronic conditions where circadian/sleep deregulation represents both a culprit of pathogenesis and a target for therapeutic intervention and prevention.