The primary goal of this K24 application is to allow Sean Mackey, M.D., Ph.D., to build and expand on his high- quality and intensive mentorship of early-career investigators in patient-oriented research (POR). Dr. Mackey is the Redlich Professor and Chief, Division of Pain Medicine at Stanford University. This K24 provides Dr. Mackey with the critical protected time for POR and mentoring that would otherwise be spent on administrative and clinical responsibilities. Dr. Mackey's mentoring plan for this K24 application builds on his currently funded HEAL project entitled: “Diagnostic and prognostic biomarkers for high-impact chronic pain: Development and validation”. Chronic pain represents a public health crisis that affects more than 100 million Americans and costs over $500 billion annually. An estimated 8% of US adults suffer from high-impact chronic pain, or pain associated with substantially restricted work, social, and self-care activities for six or more months. Subgroups of individuals respond entirely, do not change, or even worsen following pain management. Thus, robust and validated diagnostic and prognostic biomarkers are needed to identify those with high-impact chronic pain and determine the trajectory of outcome (i.e., recovery versus persistence), respectively. Therefore, our overall goal is to discover and validate diagnostic and prognostic biomarkers for musculoskeletal high-impact chronic pain. This goal will require comprehensive, multidimensional assessments with an integrated dataset and a sophisticated computational analysis pipeline to yield reliable and validated diagnostic and prognostic biomarkers. To this end, we have assembled an interdisciplinary research and clinical team to implement the HEAL initiative. Dr. Mackey's mentoring plan includes training his mentees in: 1) designing and implementing pain research studies; 2) preparing scientific papers and presentations; 3) writing successful grant applications; 4) the responsible conduct of research; and 5) successful navigation of the academic process to achieve scientific independence. This mentoring plan will be applied to the K grantees he mentors and those he oversees as the Program Director for his NIDA T32 “Interdisciplinary Research Training in Pain and Substance Use Disorders.” The mentees will engage in the training activites in three manners. The first is through direct involvement in the parent R61/R33 biomarker project via participation in aspects of the research project. The second is through seminars, journal clubs, meetings, and coursework that expands on our T32 Training Program focusing on this HEAL biomarker project. The third is through trainee-led pilot projects that leverage the parent project resources and associated multidisciplinary infrastructure. The funded HEAL project, combined with the additional mentoring time provided by the K24, will provide an exceptional POR training and mentoring platform for our large group of current and future K...