Department of Comparative Biosciences
- 1990 B.S. - Microbiology and Immunology, University of Arizona, Tucson
- 1997 Ph.D.- Pharmacology, University of Washington, Seattle
ResearchMicroglia 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), we are studying the contributions of histone modifications and microRNAs to the control of microglial phenotype.
Our research 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.
Another goal of our research 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.
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- Veterinary Pharmacology 934:552 - topics: receptor theory and pharmacodynamics; drugs of the autonomic nervous system; cardiovascular pharmacology; endocrine/steroid receptor signaling; anti-inflammatories.
- Cell and Molecular Biology Training Program
- Comparative Biomedical Sciences Graduate Program
- Endocrine-Reproductive Physiology Program
- Neuroscience Training Program
- Respiratory Neurobiology Training Program
Nikodemova, M. and Watters, J.J. 2012 Efficient Isolation of Live Microglia with Preserved Phenotypes from Adult Mouse Brain. J. Neuroinflammation. 9:147.
Friedle, S.A., Nikodemova, M., Wright, M.L. and Watters, J.J. 2011 The P2X7-Egr Pathway Regulates Nucleotide-Dependent Inflammatory Gene Expression in Microglia. Glia. 59(1):1-13.
Crain, J.M., Nikodemova, M. and Watters, J.J. 2009 Purinergic receptor expression varies with age and sex in freshly isolated brain microglia. J. Neuroinflammation, 6(1):24.
Brautigam, V.M., Dubyak, G.R., Crain, J.M. and Watters, J.J. 2008 The inflammatory effects of UDP-Glucose in N9 microglia are not mediated by P2Y14 receptor activation. Purinergic Signaling, 4:73-78.