PROJECT SUMMARY/ABSTRACT Training: The purpose of this K01 proposal is to prepare Dr. Katharine Press Callahan for a career as an independent physician-scientist focused on the ethical and social implications of genetic testing for critically ill neonates. Her long-term career objective is to conduct impactful research on the use of genetic testing for neonates using both quantitative and qualitative methods. To this end, Dr. Callahan and her mentorship team have devised a career development plan that integrates: (1) intensive mentorship from a team of mentors and advisors with whom Dr. Callahan has a track record of successful collaboration, (2) advanced training in genetic science and testing, qualitative methods, and medical simulation, and (3) an innovative research plan designed to investigate how neonatologists and parents of neonates manage the uncertainty of genetic information. Research: Genetic testing is increasingly used in ill neonates and holds promise to improve care. However, in practice, many genetic results contain substantial uncertainty, which can lead both clinicians and parents to misunderstand or misapply results, resulting in biased treatment plans. Little is known about how uncertainty affects neonatologists’ use and communication of genetic information or parents’ understanding of this information in practice. Dr. Callahan’s mentored, mixed-methods research will fill the critical need to identify and mediate potential risks that emerge as neonatologists and parents increasingly use uncertain genetic results in practice. Aim 1 will identify the types of uncertainty that neonatologists and parents perceive when they receive genetic results and examine how this uncertainty affects understanding and use of results. Aim 2 will assess the effect of uncertainty about prognosis on neonatologists’ counseling about genetic information and potential disability. Aim 3 will develop and preliminary test an information management tool that aims to improve understanding and standardize communication of genetic information and associated uncertainty between geneticists, neonatologists, and parents. Significance: Completing these aims within the context of a structured career development plan will prepare Dr. Callahan to be an independent investigator poised to execute the NHGRI vision of integrating complex genetic information into the clinical workflow in newborn medicine. Findings from this study will inform an R01 proposal to validate and disseminate the genetic information management tool developed in Aim 3.