Project Summary/Abstract Our research proposes to elucidate local and systemic immune dysregulation in rosacea with the long-term goals of developing novel preventative and therapeutic targets and improving overall health outcomes for rosacea patients. Rosacea is a common inflammatory skin disease with unclear etiology affecting over 14 million people in the United States alone.1 Toll-like receptor 2 (TLR2) is a microbe-sensing mechanism that maintains immune homeostasis in the skin through communication with commensal microbes.2-4 Therefore, we suspect that understanding the skin microbiota-host interaction is critical to elucidating the pathogenesis of rosacea. Moreover, the immune dysregulation in rosacea does not appear to be localized to the skin. There is a growing body of epidemiological evidence demonstrating that rosacea is associated with a wide range of systemic co- morbidities.40-51 Thus, it is also important to elucidate potential systemic immune dysregulation that can explain the overall disease burden in rosacea patients. Aim 1: We aim to test the hypothesis that skin dysbiosis induces transcription and expression of the components of the innate immune response implicated in the pathogenesis of rosacea. To that end, we will perform multi-omics data integration of the microbiome, transcriptome, and proteome from rosacea skin in order to delineate the microbiota-host interaction. Aim 2: We aim to test the hypothesis that there is shared immune dysregulation between the skin and systemic circulation that can explain the burden of systemic co-morbidities in rosacea patients. To that end, we will perform multi-omics data integration of the transcriptome and proteome from the skin and blood/serum in order to characterize shared molecular pathways. Dr. McGee’s career goal is to become a physician scientist with the unique expertise to apply multi-omics, data-driven, personalized strategies to treat inflammatory skin diseases and their associated systemic co-morbidities. To achieve this goal, she will undertake a combination of formalized coursework, workshops, and hands-on training in bioinformatics, computational biology, human subjects research, and clinical trials. She will also engage in career development activities by participating in a grant writing course and a K-R transition program. Dr. McGee’s research and career development will be guided by a mentoring team with several decades of combined experience in successfully transitioning their mentees to research independence. Dr. McGee’s training will take place at two prominent academic institutions: 1) Beth Israel Deaconess Medical Center, a major teaching hospital of Harvard Medical School which supports ~250 principal investigators and offers 16 institutional and 12 departmental core facilities, and 2) Harvard T.H. Chan School of Public Health, which hosts the consistently ranked #1 biostatistics program in the country and supports computational research initiatives to answer mu...