The Blood Research Institute (BRI) of The Blood Center of Southeastern Wisconsin has an established, long-term commitment to blood-related research. More than 15 Principle Investigators lead research programs in the fields of cardiovascular biology, immunology, cancer biology, control of bleeding and thrombosis and transfusion medicine. Many of these research programs utilize transgenic, knockout and normal mice in various models of human diseases. Experiments performed with these animals often require partial or lethal irradiation using a gamma irradiator. Because of the increased use of mice by BRI scientists and the lack of research animal space on the Milwaukee Regional Medical campus the Blood Center has entered into an agreement with the Medical College of Wisconsin to house the mice needed by BRI scientists in the new MCW Biomedical Resource Center. A gamma irradiator will be needed as shared equipment in this new animal facility. We request funds in this application to purchase a research gamma irradiator. Projects initiated by fourteen NIH-funded investigators and those initiated by one new investigator require this instrument to accomplish their research goals. These project titles are: Structure and Function of VWFpp; Molecular and Cellular Consequences of vWF Alteration; Robust T cell Immunity to Influenza in Human Populations; Molecular Mechanisms of Platelet Activation and Adhesion; Molecular Biology and Function of PECAM-1; Endothelial Redox Signaling Mediated by PECAM-1; Mechanisms of Vaso-Occlusion in Sickle Cell Disease: role of thrombosis; Red Blood Cell Adhesion in Sickle Cell Disease; Individual and Collaborative Roles of PLCyl and PLCy2 in T cell Activation and Development; StatS Dephosphorylation by Shp-2; Bone Marrow Derived Allo-NK Cells for Tumor Targeted Immunotherapy; The Role of Cryptic Epitopes in CD8+ T cell Mediated Tumor Clearance; Novel Function of an Important MH-Ag, H60 during GvL; Encephalitogenic T Cell Regulation of Microglial Cells; Investigating the Role of Bcl-x in Leukemogenesis by BCR/ABL; Tissue Factor Pathway Inhibitor Binding Proteins on Endothelium; CD200 Expression on Apoptotic DCs and Immune Tolerance; CD4 Regulatory T Cells Suppress Alloreactivity after BMT; Optimizing Immunotherapy for Neuroblastoma after BMT; Regulation of Engraftment and Immunity by Gamma Delta T Cells; Molecular and Cellular Mechanisms in Transfusion Medicine, Core C, Transgenic Core. A gamma irradiator is an essential piece of shared equipment that is needed for the new MCW animal facility where BRI and MCW Investigator's mice will be housed. It will support the needs of current investigators and will be available to new investigators as they are recruited during the planned expansion of the Blood Research Institute and the Medical of Wisconsin. ? ?