Titles and Education
Professor
- 1997 Ph.D.- Pharmacology, University of Washington, Seattle
- 1990 B.S. - Microbiology and Immunology, University of Arizona, Tucson
Research
Microglia (CNS resident immune cells) display extraordinary cellular plasticity to support their role in every aspect of brain health and disease. With activities ranging from resting surveillance, 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 can contribute to neurodevelopmental disorders, and exacerbate ongoing neurodegenerative pathology. Hypoxia is a common co-occurrence in many CNS diseases, yet we understand very little about how hypoxia modifies microglial responses to neural insults or disease processes. We use a rodent model of chronic neuroinflammation that is induced by intermittent hypoxia, an aspect of sleep disordered breathing. Most recently, we have become interested in how fetal exposure to intermittent hypoxia during pregnancy impacts offspring brain development and function. We study the role of epigenetic modifications to DNA and histones, and the function of microRNAs in offspring microglia, and focus on how resulting alterations in microglial activities impact neuroplasticity and neural function, including breathing disruption and cognitive behaviors. A key aspect of our research centers on understanding differences between male and female microglial responses, and how these sexual dimorphisms influence CNS function and neuroplasticity. We suggest that early life exposure to intermittent hypoxia may reprogram microglia in the developing central nervous system, predisposing to aberrant immune responses and neural disease later in life, many of which are sexually dimorphic. Our research goal is to better understand the aspects below in order to identify novel therapeutic targets to treat neural disorders.
- Impact of early life sleep disordered breathing on offspring microglia
- Role of microglia in neuroplasticity and cognitive function
- Epigenetic regulation of microglial gene transcription
- Microglial signal transduction mechanisms in paradigms of hypoxia
- Sex differences in microglial responses and their contributions to neural disorders
Responsibilities
Professor
- Veterinary Pharmacology 934:552 - topics: receptor signal transduction mechanisms; autonomic nervous system drugs; cardiorespiratory pharmacology; endocrine/steroid receptor signaling; anti-inflammatories and cancer drugs.
Graduate Training
- Comparative Biomedical Sciences Graduate Program
- Neuroscience Training Program
- Cell and Molecular Biology Training Program
- Molecular and Environmental Toxicology
- Cellular and Molecular Pathology
- Molecular and Cellular Pharmacology
Recent Publications
- Vanderplow AM, Kermath BA, Bernhardt CR, Gums KT, Seablom EN, Radcliff AB, Ewald AC, Jones MV, Baker TL, Watters JJ and Cahill ME. 2022 A feature of maternal sleep apnea during gestation causes autism-relevant neuronal and behavioral phenotypes in offspring. PLoS Biology. 20(2):e3001502. https://pubmed.ncbi.nlm.nih.gov/35113852/
- Shippy DC, Watters JJ and Ulland, TK. 2022 Transcriptional response of murine microglia in Alzheimer’s disease and inflammation. BMC Genomics. 23(1):183 https://pubmed.ncbi.nlm.nih.gov/35247975/
- Mukherjee L, Sagar MAK, Ouellette JN, Watters JJ and Eliceiri KW. 2021 Joint regression-classification deep learning framework for analyzing fluorescence lifetime images using NADH and FAD. Biomed Opt Express. 12(5):2703-2719.https://pubmed.ncbi.nlm.nih.gov/34123498/
- Ulland TK, Ewald AC, Knutson AO, Marino KM, Smith SMC and Watters JJ. 2021 Alzheimer's Disease, Sleep Disordered Breathing, and Microglia: Puzzling out a Common Link. Cells. 10(11):2907 https://pubmed.ncbi.nlm.nih.gov/34831129/
- Ewald AC, Kiernan EA, Roopra AS, Radcliff AB, Timko RR, Baker TL and Watters JJ. 2020 Sex- and region-specific differences in the transcriptomes of rat microglia from the brainstem and cervical spinal cord. J. Pharmacol Exp Ther. 375(1): 210-222. https://pubmed.ncbi.nlm.nih.gov/32661056/
- Kiernan EA, Ewald AC, Ouellette JN, Wang T, Agbeh A, Roopra AS and Watters JJ. 2020 Prior hypoxia exposure enhances murine microglial inflammatory gene expression in vitro without generalizable concomitant H3K4me3 enrichment. Front. Cell. Neurosci. 14: 535549. https://pubmed.ncbi.nlm.nih.gov/33132843/