PROJECT SUMMARY This T32 program in Investigative Rheumatology, currently in its 44th year, is dedicated to the foremost research training of biomedical scientists to prepare future leaders for the investigation of rheumatologic and immunologic diseases. The program continues with its core philosophy that advanced training in the fundamental methodologies of laboratory and translational research is essential for elucidating pathogenic mechanisms, and for devising more effective therapeutic and preventative strategies. The program will recruit the most highly qualified candidates from among clinical and post- graduate fellows with prior research achievement (MD, PhD, and MD/PhD). Training is interdisciplinary, enriched by specialized post-graduate coursework, and led by 30 faculty from the School of Medicine who are both distinguished in their respective fields of investigation and have an excellent track record of mentorship. The unique features of this program originate from: a) An emphasis on molecular mechanisms of human disease and state-of-the-art methodologies, including high-sensitivity and high-throughput profiling technologies, genomics, microbiome research, bioinformatics, and genetically-based disease modeling; b) An accomplished training faculty and existing collaborative interactions between the basic and clinical scientists; and c) A focused mission to create a scientifically-minded cadre of physician-scientists able to engage the challenges of rheumatologic diseases with incisive hypotheses and state-of-the-art experimental approaches. The program will build on existing investigative programs in autoimmunity, inflammation, and clinical immunology, and incorporate recent research initiatives. Four trainees (MD and PhD) per year are currently supported and the same number is requested in this renewal application. MD trainees typically perform clinical work in the first year of their fellowship and then enter research training under T32 support; some additionally enroll in a Masters or PhD degree-granting program. Research training is typically for 2-3 years, with subsequent training years supported by individual fellowship grants or career development awards. The inclusion in this program of both MD and PhD fellows provides a rich training experience, and fellows receive didactic and interactive instruction in biology, research methodologies, and career and ethical guidance in conducting research. This program provides trainees with a foundation in advanced research to better enable them to bridge experimental investigation with clinical information, and thus improve understanding in rheumatologic diseases. Success is measured by our accruing pool of graduates who initiate investigative careers, develop into accomplished physician- scientists, and achieve leadership positions in academic medicine.