PROJECT SUMMARY This NIH F31 grant application presents a comprehensive four-year plan designed to facilitate the professional development of Morgan Greene, the Principal Investigator, and equip her with the necessary skills to pursue an independent career as a physician-scientist. The research project's overarching goal is to unravel the transcriptomic programs driving the development of uterine natural killer (uNK) cells (Aim 1), which are essential for successful pregnancy establishment and maintenance. Additionally, the study will explore the factors that influence uNK cell differentiation into decidual natural killer (dNK) cells, a process critical to determining the pregnancy's health. Employing advanced techniques such as transcriptome-wide association studies, single- cell RNA sequencing, incubation assays, and flow-cytometry, the project's primary objective is to identify the transcriptional programs that underlie uNK cell differentiation from peripheral blood cells into dNK cells. The ultimate objective is to apply these findings to develop clinical tools that guide treatment strategies for pathological reproduction, infertility, and miscarriage, ultimately leading to improved reproductive health outcomes. The proposed training plan for Morgan Greene is supported by her project mentor, Dr. Paige Porrett, and co- sponsored by Dr. James George, and aims to establish a strong foundation for a successful career as a physician-scientist. The project-based translational approach offers an ideal training environment, with experiences designed to enhance Morgan's development in three key areas: 1) rigorous research in reproductive immunology, encompassing literature review, data evaluation, and responsible research conduct; 2) training in genetic sequencing and bioinformatics; and 3) career and professional development, including manuscript and grant writing, scientific communication, and translation of research outcomes to clinical applications. This proposal is designed to equip the PI with the advanced immunology skills necessary for a career focused on precision medicine and reproductive health outcomes as an obstetrics and gynecology physician-scientist, and drive the development of rigorous scientific research in reproductive immunology.