Project Summary Tuberculosis remains one of the leading causes of death worldwide, despite the widespread availability of effective treatment and prevention measures. To accelerate progress in reducing the global burden of tuberculosis, there is a need for new tools and approaches to identify TB early, treat it effectively, minimizing toxicities, and prevent new TB cases through preventive therapy. The overarching goal of this K24 award is to train the next generation of scientists in patient-oriented, translational research on tuberculosis. Dr. Jason Andrews is an infectious diseases physician-scientist who leads a research group focused on developing and evaluating novel tools, from the laboratory to the field. He has served as a mentor to 30 students and postdoctoral fellows and is the primary mentor for three NIH career development awards. The proposed K24 award would: 1) protect his time to mentor early career investigators in patient-oriented research, investigating critical problems in tuberculosis diagnosis, treatment and prevention; 2) enhance his skills in mentorship through guidance from a committee of highly successful senior mentors; and 3) provide him opportunities for professional development, including advanced training in pharmacogenomics, translational research and personalized medicine. These proposed activities will leverage Dr. Andrews’ long-standing research collaborations, including three active NIH-funded clinical studies in Brazil. This award would support new studies to: 1) evaluate electrochemiluminescence assays for Mtb antigen detection in exhaled breath condensates as a novel approach to active case finding for TB; 2) test for human genomic polymorphisms associated with linezolid and bedaquiline metabolism and adverse events while validating a new amplicon- sequencing pharmacogenomic assay; and 3) evaluate a novel approach to predicting isoniazid and rifapentine metabolism by simultaneously measuring transcription of and polymorphisms in drug-metabolizing enzyme genes. Overall, this proposed K24 award would provide critical support for mentoring early career scientists while advancing innovative tools to improve the diagnosis and treatment of tuberculosis.