The molecular basis for daily or circadian rhythms is a fascinating area of biology that has begun to be actively explored in terms of human health and disease. Cancer outcomes can be dramatically improved by providing therapies according to circadian time. These clinical observations and recent studies dissecting the genetics of such rhythms in model organisms form the basis of this project to develop high-throughput screens for chronotherapies against brain tumors. Dr. Herzog is a world-class biologist in this area and has brought together imaging experts and pediatric brain cancer specialists to establish a system that provides real-time monitoring of tumor status with single-cell resolution to test the cellular and molecular basis of circadian rhythms.

Final report: This two-year project established that human astrocytes and astrocytoma (brain cancer) cells express circadian rhythms in gene expression. These daily rhythms can be synchronized to daily application of a neuropeptide and correlate with daily rhythms in cAMP levels. Initial analysis of proteins associated with the cell cycle identified a candidate which may be regulated by the circadian clock. These results support the ideas that the intrinsic daily rhythms regulate cell division in these cells and are disrupted when they become tumors, creating a potential therapeutic window for timed chemotherapies to maximize efficacy and minimize side effects for pediatric gliomas.