Project Summary/Abstract Genetically engineered animal models are essential for understanding how genes can affect cancer susceptibility, development, and progression. For that reason, an animal model core service is essential for a Comprehensive Cancer Center (CCC). The Genetically Engineered Mouse Facility (GEMF) at MD Anderson Cancer Center was begun in 1988 by Dr. Guillermina Lozano to generate genetically modified animals in an effort to evaluate genes identified as possible tumor suppressors and activators. As many basic and translational research programs at MD Anderson are based on a genetic analyses of cancer, our research faculty must be able to access a strong transgenic facility. The GEMF provides a common source of state-of- the-art expertise and technical skills for Dr. Lozano and other MD Anderson investigators for the generation of their genetically engineered mouse models. Because of the individual nature of each mouse project, the GEMF provides comprehensive animal model services to all institutional investigators, regardless of prior expertise. The GEMF has provided services to more than 150 different Cancer Center members. Mouse models generated by the GEMF have been used in research reported in more than 160 publications. Dr. Jan Parker- Thornburg (this author, the co-Director of the GEMF at MD Anderson) provides essential individualized service including: 1) consultation on optimal animal models for an investigator's specific needs, 2) generation of the agreed-upon model, and 3) training in how to care for and evaluate the models produced. I bring in and test cutting-edge technologies for use by MD Anderson investigators. I am expected to develop new strategies and technologies to meet the needs of our faculty. Exciting new CRISPR/Cas9 technologies are currently being used, assessed, and refined in the GEMF. Work performed for on-site investigators (Richard Behringer, Gigi Lozano) has produced a number of insights into the technology, including describing the mosaic nature of the resulting F0 animals, and establishing new methods to increase the rate of exact targeting (homology-driven repair). Collaborations have been established to develop and test novel ways to generate conditional mutations. New Cas enzymes with different sequence specificity and those providing more faithful activity will be tested. Our results will be widely shared with other transgenic facilities as they are validated. We are highly involved with both developing and with standardizing new technologies for use at MD Anderson and in transgenic facilities worldwide.