Epigenetic regulation of microglial phenotype and function
Microglia display extraordinary cellular plasticity to support their role in every aspect of CNS health and disease. With activities ranging from resting quiescence, to inflammatory activation to neurotrophic/reparative activities, microglia participate in protecting and repairing the CNS during injury or disease. However, when their activities become dysregulated, they are thought to exacerbate ongoing pathology. Therefore, understanding mechanisms regulating their transition among phenotypes is critical. Using a rodent model of chronic neuroinflammation (intermittent hypoxia), the Watters lab is studying the contributions of histone modifications and microRNAs to the control of microglial phenotype.
Adenine nucleotide modulation of microglial cell function and signaling events in hypoxia
The research of the Watters lab focuses on delineating the role of the MAP kinase pathways and transcription factors in controlling microglial cell production of inflammatory mediators. P2X purinergic and TLR4 receptors have potent modulatory effects on microglial activities by effects MAP kinase and transcription factor activation. Selective alterations in the activity of purinergic receptors may provide a novel therapeutic target that can be exploited to minimize damage to the brain following injury.
Estrogen-mediated neuroprotection and anti-inflammatory effects in the brain
Another goal of the research of the Watters lab centers on understanding the anti-inflammatory effects of estrogen on microglial cell activation at the molecular level, by dissecting the signal transduction pathways and proteins that are modulated by estrogen in activated microglial cells. Defining the molecular mechanisms involved in the estrogen modulation of microglial cell activation and their production of inflammatory mediators, may lead to the identification of novel therapeutic targets that can be exploited to minimize the brain damage ensuing from neurodegenerative diseases and other brain disorders, to which women are predisposed.