Harold C. Simmons Cancer Center Cancer Cell Networks Scientific Program Project Summary/Abstract The focus of the Cancer Cell Networks Program is to promote investigation that will lead to a mechanistic understanding of aberrant cell regulatory networks supporting tumorigenesis. Approaches range from structural biology to animal models, and much in between. To promote cancer relevance and synergy across Simmons Cancer Center efforts, our scientific goals are broad and remain much the same as in the last submission: Goal 1) Define the mechanisms and pathways that integrate external and internal regulatory cues at the cell autonomous level. Goal 2) Establish how aberrant cell regulatory behavior contributes to cell transformation and tumorigenesis. Goal 3) Facilitate interactions with translational and clinical scientists to test the therapeutic benefit of modulating cell regulatory components. As of 2012, the Cancer Cell Networks Program is co-led by Melanie Cobb, PhD, and James Brugarolas, MD, PhD. The program has grown; it now has 46 members in 17 departments and centers. Five members are Howard Hughes Medical Institute investigators; five, including the program leader, have been elected to the National Academy of Sciences; and one is a Nobel laureate. The investigators in the CCN Program are currently supported by $33.1 million in peer-reviewed funding with $5.0 million from the NCI and $11 million from the Cancer Prevention and Research Institute of Texas (CPRIT). Through a combination of member recruiting and programmatic interactions, the CCN has had much success in engaging the discovery power of UTSW investigators for the development of new cancer focused research initiatives. Since 2009 the members of the CCN Program have authored a total of 382 publications, with 14% of them being intra-programmatic, 34% being inter-programmatic, and 23% inter-institutional with authors from other NCI-designated cancer centers.