Systemic vasculitis is a group of inflammatory disorders of blood vessels. Because knowledge of the pathophysiology of these conditions remains incomplete, their treatments are empiric, toxic, and often unsuccessful in inducing durable remissions. Insights derived from this translational research program described by Dr. John Stone, Director of the Johns Hopkins Vasculitis Center, may lead to novel methods of evaluating vasculitis patients. Dr. Stone's mentoring program for junior investigators interested in translational research provides access to a large database of well-characterized patients with vasculitis, outstanding institutional resources for clinical research training, committed mentoring, well-established collaborations within and outside of Johns Hopkins, and a research infrastructure that is essential to career development. As a programmatic research goal in the context of this application, Dr. Stone will employ current funding and existing collaborations to develop his work in proteomics. His co-investigators in this effort are collaborators at the National Cancer Institute/Food & Drug Administration (NCI/FDA) Clinical Proteomics Program, Dr. Emanuel Petricoin and Dr. Lance Liotta. Funding from the Maryland Arthritis Research Consortium (MARRC) and from the Food & Drug Administration's Office of Orphan Products Development will support these studies. The initial disease focus of this work will be Wegener's granulomatosis, using sera collected in the Wegener's Granulomatosis Etanercept Trial (A multicenter, NIAMS-funded trial in which Dr. Stone is the Principal Investigator). Other areas of research at the Vasculitis Center on which young investigators may choose to focus include: 1) the investigation of novel therapeutic approaches; 2) the role of microbial pathogens in the etiology of vasculitis; and, 3) molecular mechanisms of systemic vasculitis (under co-mentoring arrangements with colleagues whose expertise complements that of Dr. Stone), using patient samples and clinical data from the Vasculitis Center.