PROJECT SUMMARY Candidate: Paras Karmacharya, MD MS is a Clinical Instructor at Vanderbilt in the Divisions of Rheumatology & Immunology. He has a strong clinical background in rheumatology and an excellent scientific foundation in epidemiological studies from his Master’s in Clinical and Translational Science and post-doctoral research studies following clinical training. His long-term career plan is to become an independent clinical investigator and a leader in pursuing patient-centered, pragmatic research in real-world psoriatic arthritis (PsA) patients and advancing personalized medicine in PsA. To achieve this goal, he will utilize his proposed research project for hands-on training in advanced statistical methods, bioinformatics, and genetics. Research Project: This proposal will study the association of clinical and genetic heterogeneity in PsA with treatment response. Using two unique real-world PsA cohorts, Dr. Karmacharya will (1) Identify PsA phenotypes and their association with treatment response in PsA, and (2) Identify PsA patients with a high probability of responding to therapy and those with a low probability of responding to therapy in the EHR. These aims are foundational to designing future pragmatic trials leveraging the EHR to more efficiently and robustly develop personalized approaches to treatment. Career Development: Dr. Karmacharya’s career development plan integrates formal coursework with individual training from his mentors to (1) Enhance skills in advanced statistical methods, (2) Expand proficiency in applying biomedical informatics techniques to large databases through mentored hands-on training in Vanderbilt’s EHR, (3) Build foundational knowledge in genetics and through experiential learning to apply analytic techniques to a genetic biobank, and (4) Develop expertise in building and managing a prospective PsA cohort. Environment: VUMC is the ideal environment to foster Dr. Karmacharya’s development as a leader in clinical and translational research in PsA. His mentoring team includes experts in PsA (Ogdie/Ritchlin), advanced statistical methods (Byrne/Chen/Ogdie), biomedical informatics (Byrne/Barnado), and genetics (Cox). Additional institutional resources include the Synthetic Derivative (SD), a de-identified EHR with over 3.5 million subjects, and BioVU, a genetic biobank linked to the SD, and departmental support for his multicenter PsA cohort. His mentors, Drs. Crofford and Ogdie, are internationally recognized in rheumatology and PsA with successful track records of mentoring. With Vanderbilt’s institutional commitment to young investigators and expertise in biomedical informatics and genetics, Dr. Karmacharya will successfully leverage his innovative proposal for independent R01 funding.

PROJECT NARRATIVE Despite an increasing number of therapeutic options for psoriatic arthritis (PsA), a chronic progressive inflammatory disease of the skin and musculoskeletal system affecting over half a million Americans, less than a third of patients respond to therapy. This is, in part, because PsA is studied and managed as if it were a single disease. In this proposal, we will use two unique real-world PsA cohorts to better understand clinical and genetic heterogeneity in PsA and to identify those who are more likely or less likely to respond to therapy.