Project Summary This K08 career development award will provide Dr. Benjamin Korman M.D. the needed mentored training to ensure that he develops into an independent researcher who will utilize both laboratory-based experimental approaches and omics and bioinformatics to better understand the pathogenesis of systemic sclerosis (SSc). Candidate Dr. Korman is an Instructor in Medicine-Rheumatology at Northwestern University. He is dedicated to a career in academic rheumatology and has shown commitment to translational research. He completed his rheumatology fellowship at Northwestern one year ago, and has spent three years in his mentor Dr. John Varga’s laboratory where he has generated exciting preliminary data which support his current proposal. In addition to a robust publication record (15 publications, 12 original high-impact research articles including 3 first-authored original research articles, one co-first authored research article, and 3 first-authored review articles), in the last four years, he has also been successful in obtaining funding including a T32 training grant, an individual NIAMS F32 award, and an institutional BIRCWH K12 award which currently supports his work. Research Plan The research plan outlined builds on recent evidence that adipocytes modulate skin fibrosis, play a key role in SSc pathogenesis, and that a disruption in normal adipose-fibroblast homeostasis leads to unhealthy levels of adipose secreted factors in SSc. To test the hypothesis that adipocyte dysfunction is a fundamental process in SSc pathogenesis, in Aim 1, Dr. Korman will assess how mouse models of ablation or expansion of adipose tissue impact scleroderma, whether adipocytes are necessary to resist skin fibrosis, and if secreted factors mediate this effect. In Aim 2, he proposes to use ex vivo cultures of SSc fibroblasts treated with adipocyte derived factors to determine the mechanism as to how adipocytes exert their effects and which secreted factors may be relevant to SSc. To better understand the cellular regulation of these processes, he will utilize RNA-Seq to assess whole genome expression and bioinformatics to interpret this data. If successful, this work should lead to the development of biomarkers and therapeutics for SSc, a disease which currently lacks both. Career Development Plan Dr. Korman will achieve his career goals through a career development plan that consists of formal coursework, and intensive mentorship that will teach him to independently perform translational research which utilizes mouse models of fibrosis, ex vivo culture systems, RNA-Seq, and bioinformatics. His primary mentor is Dr. John Varga, a world expert in SSc and fibrosis with over 20 years of continuous NIH funding, hundreds of seminal papers in SSc, and an outstanding record of mentoring. Dr. Varga will ensure that Dr. Korman obtains the knowledge and appropriate laboratory skills necessary to head a lab focused on SSc. His co-mentor Dr. Davuluri is the foremost ex...