The High-throughput Screening Core Facility (HTSCF) was established in 2003 to support the Institution's growth in chemical biology and functional genomics. The HTSCF's ongoing mission continues to support such efforts. Bioactive compounds are used as chemical tools to probe biological processes. The identification of novel molecules requires a broad range of tools including robust assays, large collections of chemicals, HTS technologies, and knowledge in hit validation and characterization steps. The HTSCF has modern robotics, custom built screening data management databases, chemical screening libraries, RNAi screening libraries, assay development and industrialization expertise, screening data analysis and management. The Core is equipped with two custom-built linear track robotic platforms harboring several dispensers, microtiter plate readers, automated microscopes among other instrumentation enabling both invitro target based and cell based assays to be routinely performed. Screening data acquisition and management is handled through a suite of custom built software. The compound library has grown to 400K chemicals; and contains a wide variety of natural products. The RNAi libraries have also grown to include both siRNA and shRNA capabilities covering 22K genes. Glycerol stocks of individual shRNA hairpins are provided as a service. One example of important work facilitated by this work was a screen against mutant EGFR in human lung cancer cell lines by the Varmus lab. The screening efforts led to the identification and characterization of four classes of small molecules overcoming the mutations. The broad range of services and collaborative work provided by the (HTSCF) has supported the research of 48 investigators in the past year. During the past grant period the work of the Core has contributed to 27 publications of researchers from 8 research programs.