Deneen’s research will focus on the role astrocytes play in brain circuit control. Astrocytes are a form of glial cells that make up most cells in the central nervous system and play essential roles in brain circuit activity.
“Over the past 20 years our knowledge of astrocytes has undergone a renaissance highlighted by the identification of dynamic physiological activities, key roles in circuit function and diverse molecular properties,” Deneen said. “Central to the physiological activities of every cell are transcription factors (TFs), but their exact function in astrocytes is not fully defined. My work has focused on the molecular, cellular and physiological roles that TFs play in astrocyte function in the adult brain.”
Deneen and his lab colleagues have found that Nuclear Factor I (NFI)- and Sox- family TFs exhibit universal expression in astrocytes across all regions of the brain but have region-specific roles in mature astrocytes. Hippocampal astrocytes require a type of NFI to maintain their functional integrity, while olfactory bulb astrocytes require a form of Sox.
“These findings are the foundation for the work the Outstanding Investigator Award will support,” Deneen said. “We plan to use these region-specific transcriptional dependencies for astrocyte function to provide an entry point for understanding how astrocyte diversity is encoded, what functions they are responsible for, and how they regulate brain circuits.”
They also will work to uncover how astrocyte dysfunction is associated with a host of neurodegenerative diseases, including Alzheimer’s Disease.