The Functional Genomics Shared Resource (FG) enables Cancer Center members to perform genetic screens in cells in a rapid and effective manner. To this end, FG has established a standard workflow that starts with a feasibility assessment, transfection optimization, assay development, pilot screens, full-scale screening, data analysis, and verification of targets identified. The initial focus of FG has been siRNA screening, and to date FG has undertaken 19 projects addressing questions ranging from basic cancer biology to activity profiling of compounds with therapeutic potential. The individually arrayed siRNA Libraries in the core include a large human druggable collection, with 4 individual siRNAs to 7,200 genes, a similar mouse collection, and a variety of focused siRNA libraries targeting kinases, protease, GPCRs, and a Burnham-designed 1,100 gene target Ubiquitinome set The latter supports the strong ubiquitin interest group in the Signal Transduction Program. Given the increasing demand and role for functional genomics approaches, after two years of development. Functional Genomics is now proposed as new Shared Resource. During the next funding period, FG plans to enhance its services repertoire to include gain-offunction screening via cDNA over-expression as well as microRNA mimic and functional inhibitor screening capabilities. The facility will also increase gene coverage with a chemically modified siRNA library against the entire human genome, and implement lentiviral-mediated screening methods to be able to address cancer-relevant cells that are difficult to transfect and are out of reach for functional genomics studies using present technology. The Functional Genomics Shared Resource leverages the remarkable resources available in the Center for Chemical Genomics (in which the Chemical Library Screening Shared Resource is located), including liquid handling, automation, multimode plate readers, and high content screening equipment and expertise. In the past year. Dr. Tariq Rana joined Burnham and he serves as the Scientific Director of the FG core. As a renowned leader in the mechanisms of RNA interference (RNAi) and in RNA biology. Dr. Rana's expertise will provide critical guidance for this new Shared Resource. Overall, $99,609 in CCSG support is requested in the first year, representing 20.3% of the total estimated annual operating budget for the Functional Genomics Shared Resource.