This Lymphoma SPORE application from the James P. Wilmot Cancer Center (JPWCC), University of Rochester, and the Arizona Cancer Center (ACC), University of Arizona provides a broad based, translational research program studying several major unresolved issues in the lymphoma biology. Specifically the projects will focus on several novel, targeted therapeutic agents either in development or approved for the treatment of three of the most common non-Hodgkin's lymphomas, namely diffuse large B-cell, follicular and mantle cell lymphoma. We will initially seek to elucidate mechanisms of action and/or resistance both in vitro, and in carefully developed model systems;then pilot clinical trials with an emphasis on correlative studies will be designed and conducted to validate these mechanisms. Investigators at the JPWCC and the ACC, long-time collaborators, lead each of the programs. The clinical and pathologic resources of the Lymphoma Committee of the Southwest Oncology Group are also integrated into this program. Projects include: Research Project 1: Targeting Aurora Kinase in Aggressive B-cell non-Hodgkin's Lymphoma, Project 2: Optimizing Redox Modulation as a Therapeutic Strategy for NHL. Project 3: Potentiating Proteasome Inhibitor Activity in NHL. Project 4: Characterization of Lymphoma-lnitiating Cells.