In response to RFA: AR-05-005, we propose to create a Center of Research Translation entitled """"""""Center for Lupus Research"""""""". The Center will be focused on the study of Human Lupus Erythematosus. It will incorporate the efforts of immunologists (both basic and translational), and physician-scientists with expertise in the research and care of patients with lupus from several Institutions. The goals of the Center are to understand the role of neutrophils and monocytes in lupus pathogenesis, to determine the checkpoints where mature B cells break tolerance against self, and to develop better markers of disease activity and response to therapy for patients with Systemic and Cutaneous Lupus. Objectives: The Center will establish: i) The role of neutrophils, monocytes and B cells in SLE pathogenesis, ii) The factor(s) responsible for the unabated DC differentiation in SLE, iii) B cell tolerance checkpoints of mature B cells, iv) Markers of disease activity, v) Markers predictive of response to therapy in patients with lupus nephritis, and vi) Markers predictive of systemic evolution of local (cutaneous) disease. Deliverables: i) Extensive microarray database of blood SLE samples and of blood and skin cutaneous lupus samples, ii) Robust, transcriptional and protein-based assays to assess SLE disease activity and to predict response to therapy, iii) Knowledge on the role of monocytes, neutrophils and B cells in SLE pathogenesis, iv) Pre-clinical therapeutic value of TLR7/8/9 inhibitors. Our proposal meets the RFA requirements with regard to: 1) The overarching aim of disease-specific research translation, 2) Inclusion of resources and an administrative structure to facilitate research translation, 3) Inclusion of projects that are translational in nature, directed at elucidating the relevance of basic research to human disease: all 4 main projects involve the study of SLE patient cells and/or tissues. 4) Multi-investigator and Multidisciplinary team;Synergy for the theme: 7) The CORT is focused on one of the diseases in the NIAMS mission: human lupus. 8) There is existing research base supporting each of the projects demonstrated by numerous publications in highly visible journals. 9) All projects include patientoriented research, including a) mechanisms of human disease and/or b) development of new tools to assess disease activity. 10) The CORT Advisory Group represents scientific expertise in SLE and a lay person. An Education Component will establish an annual Symposium and Workshop to educate scientists in the field of lupus research. This component will also maintain a website. Thus, the Center will provide 1) novel markers for disease follow up and response to therapy;and 2) novel molecules relevant for disease pathogenesis and 3) novel therapeutic targets.
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