PROJECT SUMMARY / ABSTRACT This is a proposal for a K24 Midcareer Investigator Award in Patient-Oriented Research for Ami A. Shah, MD, MHS of Johns Hopkins University School of Medicine. Dr. Shah is an Associate Professor of Medicine in the Division of Rheumatology, Deputy Director for the Rheumatology Precision Medicine Centers of Excellence clinical programs, and Co-Director of the Johns Hopkins Scleroderma Center. Dr. Shah has spent the majority of her career and scholarship focused on patient-oriented research in systemic sclerosis (scleroderma) and in investigating the relationship between cancer and autoimmunity. Scleroderma is a complex, multisystem rheumatic disease that manifests very differently among patients with the same diagnosis. There is heterogeneity in symptoms, trajectory of disease, timing of events, and response to therapy. While many risk factors have been identified for specific scleroderma complications at the population level, these have not been easily translatable to clinical practice at the patient level. This has been due to many factors including difficulty (i) capturing multivariate patient-specific disease trajectories, (ii) modeling the complex interplay between organ system parameters over time, and (iii) utilizing knowledge gained from trajectories of other patients who share scleroderma subgroup characteristics. In this proposal, the applicant seeks to harness rich clinical data through the Johns Hopkins precision medicine platform and develop novel computational methods to generate personalized risk estimates of major clinical events in scleroderma. She will utilize an innovative strategy to apply and test these new insights in a clinical setting. By embedding estimated trajectories and probabilities of major events into a patient level data visualization tool that updates in “real-time,” she will test whether these new discoveries can influence provider risk estimation and future diagnostic and therapeutic decision-making. Lastly, she will utilize phenotypic trajectories as a platform to identify candidate biomarkers at baseline that associate with long-term disease progression in scleroderma, as this may provide insight into patient subgroups who could benefit from intensive screening and treatment strategies. These aims will serve as an outstanding vehicle for career development and growth for Dr. Shah’s mentees, opening new fields of inquiry and developing novel precision medicine approaches in scleroderma.