ABSTRACT – FUNCTIONAL GENOMICS SHARED RESOURCE The central goal of the Functional Genomics Shared Resource, which is managed by the Cancer Center, is to provide services and tools for Center members to perform RNAi and CRISPR-CAS9 genetic screens in cultured cells. Core staff interact with Center faculty members throughout their projects, starting with project conceptualization and feasibility assessment through to the final verification of targets identified in the screens. The Core utilizes the extensive amount of HTS equipment available in the Prebys Center and the Chemical Library Screening Core. In addition to the wealth of expertise brought by the staff, the Core serves as a repository for reagents, assays, and technical information, which are shared with Cancer Center researchers. The Core provides a variety of libraries for functional genomics analysis, including a genome-wide siRNA library, and comprehensive miRNA activator and inhibitor libraries, broad shRNA libraries, as well as targeted arrayed and genome-wide pooled CRISPR libraries. The Core's primary effort is dedicated to genetic screening via RNAi and CRISPR-Cas9, although significant time is also currently dedicated to engineering of cell lines. Within the Core, the main laboratory focuses on cellular genetics, while the viral vector laboratory specializes in high-quality vector preparation in a centralized facility with expert staff, and produces an array of sophisticated viral systems to enable nucleic acid delivery. Both laboratories are also actively involved in developing tools tailored to the specific needs of Center researchers. Functional Genomics operates in close connection with other Shared Resources at SBP. Thus, the Core utilizes automation and high-throughput imaging support from the adjacent Chemical Library Screening Shared Resource; interacts with the Bioinformatics Shared Resource to perform statistical analysis of the raw data and design custom CRISPR libraries; and uses the sequencing services of the Genomics Shared Resource to execute CRISPR-Cas9 screens. Overall, the Functional Genomics Core has strived to maintain its place at the forefront of cellular genetics and nucleic acid delivery by adopting state-of- the-art technologies, implementing methods to fill technology gaps, and adapting methods to fulfill the specific needs of the Cancer Center. In the past 5 years, the Core was used by a total of 45 Center members representing all three programs, and it supported at least 29 cancer-related publications by Cancer Center members.