PROJECT SUMMARY Candidate: Dr. Erin Wilfong, M.D., Ph.D. is a Clinical Instructor at Vanderbilt University Medical Center in the Divisions of Allergy, Pulmonary, & Critical Care Medicine and Rheumatology & Immunology. She has a strong clinical background in both rheumatology and pulmonology with an excellent scientific foundation in chemical biology and translational immunology from both her Ph.D. studies and her post-doctoral research studies following clinical training. Her long-term career plan is to become a leading physician-scientist in inflammatory myositis focused on the use of cutting-edge technologies to identify disease pathogenesis and novel therapeutic targets. To achieve this, her immediate goal is to (1) learn the requisite bioinformatic techniques to independently analyze high-dimensional immunophenotypic and transcriptional profiles and integrate these profiles with clinical outcomes, and (2) apply molecular immunology techniques to determine dysregulated pathways in IIM-specific cell populations. Research Project: This proposal will study the underlying immunologic heterogeneity of IIM and identify associations between immune/transcriptional signatures and clinical characteristics. Dr. Wilfong will (1) identify immune signatures and transcriptional aberrancies in IIM using a cross-sectional IIM cohort and (2) correlate immune features with ILD progression in a longitudinal IIM cohort. She will also take a prior single-cell RNA- Seq finding and (3) perform mechanistic studies investigate how upregulation of the redox sensor TXNIP alters immunometabolism in Jo1+ anti-tRNA synthetase syndrome. Career Development: Dr. Wilfong’s career development plan integrates formal coursework with personalized training from her mentors and collaborators to: (1) master R programming to facilitate analysis of immunophenotypic and transcriptional datasets using cutting-edge analytic tools, (2) learn biostatistical principles necessary to appropriately correlate immunology findings to clinical phenotypes, (3) characterize cellular function using in vitro assays, and (4) develop the leadership and communication skills necessary to become a principal investigator who applies the scientific findings and methodologies from this K08 award towards a future translational immunology R01. Environment: VUMC is the ideal environment to foster Dr. Wilfong’s development as a leader in translational immunology and inflammatory myositis. Dr. Wilfong’s mentoring team includes experts in inflammatory myositis (Crofford/Aggarwal), immunometabolism (Rathmell), single-cell RNA-Seq (Kropski), and computational immunology (Georgiev). In addition to having the necessary mentors and equipment, 71.3% of Vanderbilt University Medical Center career development award recipients (n=236) have successfully received R level funding since 1999. Drs. Crofford and Rathmell have successfully trained many physician-scientists and will ensure that Dr. Wilfong becomes an independently fu...