PROJECT SUMMARY VA Northern California Health Care System (VANCHCS) serves over 500,000 Veterans and is one of the largest catchments in the country, including a large rural component. VANCHCS operates research projects at both the Sacramento VA Medical Center (Mather) and the VA Martinez Outpatient Clinic. We conduct research to discover knowledge, develop VA scientists and health care leaders, and create innovations that advance health care for Veterans and the nation. Our Biomedical Laboratory Research & Development Service conducts preclinical and clinical research to understand life processes from the molecular, genomic, and physiological levels regarding diseases affecting Veterans, with a major emphasis on cancer. Some key objectives of our research program are to identify new cancer therapeutic targets and better understand the molecular mechanisms and pathways underlying cancer progression, such as therapeutics resistance. To accomplish these goals, we employ functional genomics, metabolomics, bioinformatics, genetics, and pharmacological approaches to determine the physiological and pathological functions and action mechanisms of key regulators to elucidate the mechanisms of action of the new therapeutics. To help our research program reach these goals, which will directly benefit our Veterans, we are requesting funds for a Cell Imaging Multi-mode Reader. This system would allow us to greatly expand the breadth of our research capabilities at VANCHCS. For example, our research program would be able to perform brightfield and immunofluorescence live cell imaging on both 2D and 3D cell cultures, as well as a multitude of biochemical assays, such as cell viability and toxicity, cell migration and invasion, apoptosis and necrosis, DNA damage, phagocytosis, phenotypic assays, and metabolomic assays, to name a few. This single piece of equipment would strongly enhance our current Cancer Research program and increase our ability to apply for competitive grant funding. Currently, our Cancer Research group has several VA- and NIH-funded studies that would benefit directly from this Cell Imaging Multi-mode Reader; 1) function and mechanism of small molecules in castration resistant prostate cancer; 2) periclinal mechanistic and immunologic studies for a novel lymphoma treatment; 3) therapeutic targeting steroid sulfatase and /or Wnt5A for advanced prostate cancer; 4) targeting tumor metabolism in prostate cancer; 5) develop potent and deliverable therapeutic peptides and small molecule inhibitors as a novel therapeutic for Veteran colorectal cancer patients. Ultimately, our goal is to identify cancer relevant therapeutic targets and develop novel therapeutics to better treat Veterans.