Project Summary/Abstract Renal transplantation has become the treatment of choice for patients with end-stage renal disease. However, acute renal allograft rejection (ARAR) remains a major complication after kidney transplantation and is associated with significant morbidity and mortality. Importantly, ARAR remains the strongest predictor of long-term renal allograft injury and survival. Currently known risk factors do not allow for the accurate assessment of ARAR risk. In addition, we currently lack a non-invasive, cost-effective clinical test to diagnose ARAR. The development of novel urinary exosomes represents promising prognostic tools for ARAR risk assessment. The goals of this Mid-Career Investigator Award are to expand Dr. Reza Abdi’s patient-oriented research program towards the development of better diagnostic and prognostic strategies for ARAR in renal transplant patients, further enhance Dr. Abdi’s mentoring skills, and provide him with the resources and support to foster the development of trainees interested in patient- oriented research in transplantation. This research proposal is built upon the candidate’s prior research identifying ARAR biomarkers in transplantation and is strengthened by his multidisciplinary collaborations. These projects offer a unique opportunity for mentees to train in patient-oriented clinical and translational transplantation research that is at the intersection of immunology, biomarker research and transplantation. From this training vehicle, mentees will gain skills to carry out patient-oriented research in transplantation, learn to apply cutting-edge exosome and mRNA profiling and analysis and gain hands-on experience in translational research in ARAR. The rich resources and infrastructure at Harvard Medical School and the Brigham and Women’s Hospital Renal Division/Transplantation Research Center provide an outstanding scientific research environment to train the next generation of researchers in transplantation. These studies will not only help identify novel immunogenetic biomarkers for predicting ARAR and help in the creation of a clinical tool for diagnosing ARAR, but will also advance our understanding of the pathogenesis of ARAR and greatly assist in the development of innovative therapies in renal transplantation.