Current Research and Scholarly Interests
Stem cell function requires both the establishment and maintenance of particular epigenetic states. Perturbation of the epigenetic status of stem cells may compromise both self-renewal and multipotency. Work from our lab has identified the Forkhead family transcription factor, FoxO3, as a regulator of adult neural stem cell (NSCs) quiescence, which prevents the depletion of this population of cells. Along with recent evidence that Forkhead family members act as pioneer factors in the opening of compacted chromatin, these studies raise the possibility that FoxO3 regulates the epigenetic modifications required for the proper self-renewal and multipotency of NSCs. To explore this possibility, I am currently examining the regulation of local and global chromatin states by FoxO3 in NSCs. In addition, I am employing high-throughput approaches to identify FoxO3 binding sites in NSCs at the genome-wide level. Finally, I am exploring the interactions between chromatin modifiers and FoxO3, which may function to remodel chromatin and control FoxO3-mediated transcription. These studies will provide novel insight into the epigenetic mechanisms regulating normal NSC function and lay a foundation for understanding the etiology of age-related neurodegenerative diseases.