ABSTRACT This K24 renewal builds upon the successful clinical research and mentorship performed by the candidate, Sylvia Becker-Dreps, MD, MPH. As a natural extension of Dr. Becker-Dreps’ previous work on human norovirus (NoV), this proposal expands her research skillset to investigate maternal protection against NoV in early childhood. Understanding how the maternal-child interface acts to protect against NoV can guide interventions to reduce childhood NoV disease burden. In addition, she plans to purposefully integrate trainees into her research. Candidate: Dr. Becker-Dreps is a physician-scientist dually appointed in Family Medicine and Epidemiology. Her research focuses on the epidemiology and prevention of viral gastroenteritis in children. She employs a multidisciplinary approach combining robust field epidemiology with state-of-the-art laboratory methods. Her group contributed to understanding poor rotavirus vaccine performance in low-resource settings and characterized the natural history, clinical characteristics, and risk factors for sapovirus gastroenteritis. During the first K24 award period, she shifted her focus to NoV, and answered fundamental questions about the development of NoV immunity to inform vaccine development. The proposed career development activities will expand Dr. Becker-Dreps’ skillsets to allow her to characterize components of maternal protection against NoV in early life. Research Plan: The proposed research builds on recent epidemiological findings showing that maternal glycobiology is associated with protection against NoV. Specifically, her group found that children of mothers who are “secretors” of fut-2-dependent fucosylated oligosaccharides have a lower risk of NoV. Using existing data and biobanked samples from a Nicaraguan birth cohort including 419 breastfeeding mother-child dyads, she plans to elucidate differences in breastmilk oligosaccharide composition and NoV-specific antibodies in breastmilk and serum by maternal secretor status, and to understand their independent contributions to the risk of NoV in early life. She will also determine whether differences in infant gut microbiome composition are associated with the risk of NoV gastroenteritis. Mentoring Plan. Dr. Becker-Dreps has an established track record of successfully mentoring trainees in patient-oriented research, and for attracting trainees from groups underrepresented in science. Trainees will be offered access to existing data and samples from two large maternal-child cohort studies and will be encouraged to identify independent research projects that they can take ownership of. To complement her one-on-one project-based mentorship, she will leverage UNC’s extensive resources, including from UNC’s CTSA, NIH-funded training programs, and through a new leadership role at the UNC Office of Global Health Education. Without K24 funding, her available time for mentorship is limited. She plans to use protected time afforded by the K24 renewal t...