Personal Statement

My research has long focused on the regulation of chromatin structure and function, and has laid the foundations for identifying how chromatin structure is related to the regulation of transcription, DNA replication, and the repair of DNA double-strand breaks. My prior research covered three main areas: the role of H2B ubiquitylation in transcription; the relationship of H2B ubiquitylation to DNA replication; and the role of nucleosome remodeling in the repair of DNA double-strand breaks.

Over the past several years, I became interested in the phenomenon of cellular quiescence, a stable non-growing state that defines most adult stem cells. Using a budding yeast model in which quiescent cells are formed in the context of chronological aging, my laboratory initiated a large-scale study to define the transcriptome and epigenome of quiescent cells. We found that quiescent cells, although not transcriptionally active, retain a large cohort of stored RNAs, significant levels of RNA polymerase II, and a histone modification landscape that is associated with active transcription. We have hypothesized that this landscape poises quiescent cells for rapid re-entry into the cell cycle when they are stimulated to resume growth.

This research has provided the foundation for additional studies on the properties of quiescent cells: the temporal-spatial program of DNA replication when quiescent cells re-enter the cell cycle; the response of quiescent cells to exogenous DNA damage; and the role of histone modifications in the formation and survival of quiescent cells, which is related to the control of chronological lifespan. Our preliminary studies in these areas revealed several properties of quiescent yeast cells that could serve as paradigms for understanding the unique features of quiescent cells in more complex developmental systems and the mechanisms they use to preserve genome integrity.

In addition to overseeing an active research program, since 2004 I have served as co-leader of a basic science research program (currently the Cellular and Molecular Oncology Program) at the University of New Mexico Comprehensive Cancer Center. In this role, I oversee all aspects of the Program, by helping to define its scientific focus and overseeing recruitment of members, intra- and inter-programmatic interactions, funding opportunities, and training.