Retinoblastoma is the most common malignant eye tumor in children. The gene that causes it—RB1 gene— has been implicated in the development of many human cancers. Although the cell of origin of retinoblastomas is unknown, a recent study suggests that these tumors have features of a cone photoreceptor precursor cell and express high levels of the photoreceptor transcription factor, Crx. Crx is a master regulator of photoreceptor gene expression, and thus may also be a master regulator of gene expression in retinoblastoma. In collaboration with J. William Harbour, MD, Dr. Corbo and colleagues will test this idea by using a cutting-edge genomic technique, chromatin immunoprecipitation, followed by next-generation sequencing (ChIP-Seq), to elucidate the structure of the Crx-regulated gene network in retinoblastoma. This information will provide a blueprint of the genes active in retinoblastoma and will yield novel insights into the mechanism of tumor formation. As part of this project, Dr. Corbo’s lab will also test a new treatment for retinoblastoma in a model system, in which they attempt to force the differentiation of the tumor into rod photoreceptors. If successful, this approach could eventually lead to a new form of eye-sparing therapy for retinoblastomas. Such eye-sparing therapy would be a significant advance, since children diagnosed with retinoblastoma currently may require surgical removal of one or both eyes.