The Cellular Transformation Program within the Abramson Family Cancer Research Institute (AFCRI) encompasses investigators utilizing diverse scientific approaches to study basic mechanisms contributing to tumor initiation, progression, and cell survival. This AFCRI Program is now composed of ten faculty, including Drs. Craig Bassing, Donita Brady, Eric Brown, Luca Busino, Roger Greenberg, Robert Faryabi, David Roth, Katy Wellen, Eric Witze, and Xiaolu Yang, who probe fundamental mechanisms underlying cancer cell metabolism, epigenetics, genome integrity, cell polarity, maintenance of the proteome, and signal transduction. Each faculty member leads an independent state-of-the-art research program, yet they have maintained cohesiveness through their common interests in how these mechanisms combine to cause normal cells to adopt malignant characteristics. Over the past fifteen years, investigators in this program have been highly prolific, and their research has been published in top scientific journals, such as Science, Nature, Cell, Nature Cell Biology, PLoS Biology, Cell Metabolism, Molecular Cell, and Cancer Discovery. Moreover, basic findings from members of the Cellular Transformation Program are currently being translated into novel therapeutic approaches to treat diverse malignancies, such as breast cancer, prostate cancer, B cell lymphoma, pancreatic cancer, and malignant melanoma.