ABSTRACT The past 15 years has seen a paradigm shift in our understanding of the complex mechanisms underlying autoimmune diseases with a greater understanding of the interplay between innate and adaptive immune system components, the mechanisms that lead to innate and adaptive immune mediated tissue destruction, the relevance of animal models to human disease, and the factors needed to generate functional transplant tissue. To capitalize on all of these insights and develop novel therapeutic strategies that block autoreactive responses and also permit the repair and/or replacement of damaged organs, will require a next generation of scientists with a broad understanding of basic immunology, cell biology, molecular biology, systems biology and informatics. The proposed Training in the Molecular Basis of Autoimmunity and Autoinflammation will train predoctoral investigators in these important areas by bringing together highly skilled and collaborative mentors from multiple disciplines, with the ultimate goal of developing new therapies for these debilitating diseases. We have also learned that an array of susceptibility genes are shared among autoimmune diseases, indicative of common pathways. A better understanding of how these susceptibility genes promote the loss of tolerance and hyperreactivity will also be key to effective treatments for autoimmune diseases. To train investigators to meet these challenges of scientific inquiry, our training environments must embrace cross-disciplinary themes and provide both state-of-the-art research opportunities in this area, and also provide training in other aspects of career development. Therefore, the specific goals of this program will be to: (1) provide talented PhD candidates with conceptual and technological skills to tackle meaningful, clinically relevant topics in the area of autoimmunity; (2) facilitate communication and collaborative interactions amongst trainees and training faculty; (3) provide opportunities for the translation of research discoveries to the clinics; (4) establish mechanisms for recruiting increased numbers underrepresented minorities to postdoctoral positions at this institution; (5) provide trainees with strong oral presentation, manuscript writing, grant writing, networking, and other essential career development skills; and (6) provide trainees with opportunities to participate in local, national, and international meetings where they can share their own research findings. The program is highly cross- disciplinary, incorporating 18 accomplished investigators as mentors who represent a broad spectrum of research expertise and technologies that are being applied to the study of autoimmune/autoinflammatory conditions. The training faculty includes MD and MD-PhD scientists engaged in basic and translational, disease-oriented research. Faculty members are already involved in highly productive collaborations and have extensive experience in predoctoral training. The program co-directors will be advised by both the training faculty and an External Advisory Committee comprised of distinguished scientists/training grant directors with interests in autoimmunity and autoinflammation. Importantly, the program directors will work closely with the UMMS Office of Career Development to provide training in critical career skills that will further enable trainees to carry their research accomplishments forward to successful academic careers.

PROJECT NARRATIVE The past 15 years has seen a paradigm shift in our understanding of the complex mechanisms underlying autoimmune diseases with a greater understanding of the interplay between innate and adaptive immune system components, the mechanisms that lead to innate and adaptive immune mediated tissue destruction, the relevance of animal models to human disease, and the factors needed to generate functional transplant tissue. To capitalize on all of these insights to develop novel therapeutic strategies that block autoreactive responses and also permit the repair and/or or replacement of damaged organs, will require a next generation of scientists with a broad understanding of basic immunology, cell biology, molecular biology, systems biology and informatics. The proposed Training in the Molecular Basis of Autoimmunity and Autoinflammation will train predoctoral investigators in these important areas by bringing together highly skilled and collaborative mentors from multiple disciplines, with the ultimate goal of developing new therapies for these debilitating diseases.