Neuroscience Faculty

Chris Davis, PhD, investigates the effects of sleep deprivation at the molecular, physiological, and behavioral levels. He demonstrates the consequences of sleep loss on cognitive performance, brain chemistry and slice electrophysiology. He was the first to demonstrate the effects of sleep loss by measuring long-term potentiation in the hippocampus and correlated this physiologic finding with molecular (cortactin, long-noncoding RNAs, microRNAs) and behavioral assays of performance such as a novel floor vibration maze. The Davis Lab has also shown that stress confounds the effects of sleep loss and that the drug Neurexan mitigates stress-induced insomnia in model systems.

Marcos Frank, Phd, is investigating the role of glial cells in the accumulation and discharge of sleep pressure and synaptic plasticity in vivo. The Frank Lab has shown that astrocytes play a central role in controlling sleepiness through the release of glio-transmitters. Glial cells are known to influence synaptic plasticity and may be key players in both the regulation of sleep and the facilitation of downstream benefits of sleep. Frank’s lab measures brain activity in vivo (electrical and intracellular calcium) and correlates this data to protein levels and gene expression and to quantitative measurements of sleep and wakefulness. This combination of approaches facilitates a robust understanding of how basic neurophysiology correlates to behavioral parameters of sleep.

Sleep is also critically important to brain development in the early postnatal period. Basic processes of neural development have been established in sensory systems making them particularly well suited to study the role of sleep in neurodevelopment. Frank’s lab studies the effect of sleep on the development of the visual system and has shown that critical stages of physiological and neuroanatomical development in the visual cortex are enhanced by sleep. His lab is now working to determine the molecular mechanisms responsible for this effect of sleep.

Jason Gerstner, PhD, has shown that Fabp7, a glial-enriched transcript, has synchronized circadian expression across all regions of the mouse brain, and is necessary for normal sleep behavior. When Fabp7 is overexpressed in a transgenic fly model, the resulting Fabp7-induced sleep produced enhancement of long-term memory. This Fabp7 overexpression was also shown to rescue a sleep fragmentation phenotype in a fly model of Alzheimer’s disease. He discovered that Fabp7 protein was localized to perisynaptic astrocytic processes, and that this localization may be mediated by local cytoplasmic translation mechanisms. The temporal and spatial expression pattern of Fabp7 may provide mechanistic insight into neural-glial interactions that influence synaptic plasticity in a manner coordinated with sleep and circadian rhythms, which are thought to influence the etiology of neurological disorders and neurodegenerative disease.

Kimberly Honn, PhD, conducts laboratory sleep and sleep deprivation studies with specially designed computerized or simulated tasks to identify particular cognitive functions that are most vulnerable or most resilient to the effects of sleep loss. She aims to understand the mechanisms by which sleep loss affects the brain such that interventions can be designed to protect against sleep loss-related errors. Honn’s research extends into real-world settings with field research projects studying sleep, shiftwork schedules, and performance in industries including aviation, rail, and long-haul commercial trucking.

Darrell Jackson, PhD, investigates sex differences in post-stroke injury in premenopausal, postmenopausal female and aged matched males’ rodent subjects at the molecular and physiological levels. Specifically, he has demonstrated that following ischemic-reperfusion injury, hippocampal glutamatergic AMPA receptor undergo composition switch, changing from a calcium impermeable GluA2-containing AMPA receptor to a calcium permeable GluA2-lacking AMPA receptor. GluA2-lacking calcium-permeable AMPA receptors are known to mediate delayed neuronal death of hippocampal neuronal cells following stroke injury. In contrast, ischemic-reperfusion insult to premenopausal females up-regulates GluA1 and GluA2 AMPA receptor subunits at the protein levels as well as at the transcriptional levels. Previously, the Jackson lab has identified the reactive oxygen species generation NADPH Oxidase as the underlying factor responsible for the internalization and degradation of GluA2-containing AMPA receptor following post-ischemic injury to hippocampal neurons in male subjects. Recently, the Jackson lab has demonstrated that NADPH oxidase activation is suppressed in premenopausal female hippocampus following post-ischemic injury. Currently, the Jackson lab is investigating the role of estrogen signaling pathways and related neuronal pathways in the hippocampus that suppressed post-stroke NADPH oxidase activation and expression of calcium permeable AMPA receptors.

The Kapás Lab is also investigating aspects of systemic physiology and their interaction with sleep. He has shown that there is communication between the gastrointestinal system and the brain via the vagus nerve (CN X) that impacts sleep. He is also interested in the interaction of the microbiome as well as immune responses in controlling the quality, timing and amount of sleep.

James M. Krueger, PhD is a Regents Professor at Washington State University (WSU).  His BS degree is from the University of Wisconsin, PhD degree from the University of Pennsylvania, and Doctorem Medicinae Honoris Causa from the University of Szeged, Hungary.  His postdoctoral work was at Harvard Medical School. He co-founded the Sleep and Performance Research Center at WSU-Spokane.  Dr. Krueger received several awards including the Distinguished Scientist Award from the Sleep Research Society, a Javits Award from NIH/NINDS, and the Eminent Faculty Award at WSU.  He served as President of the Faculty Senate at the University of Tennessee Medical Center, and as Chair of his WSU department.  He was elected to the Washington State Academy of Sciences in 2012.  He published 412 manuscripts, 394 abstracts, (H-index [27,160 citations]), given 331 symposium talks and seminars, and been issued 6 patents. His major accomplishments include the characterization of; a) the supra-normal EEG delta waves occurring during NREMS post sleep loss; b) Factor S as a muramyl peptide; c) the physiological roles of cytokines in sleep regulation; d) multiple other sleep regulatory substances; e) the dramatic changes in sleep over the course of infectious diseases, f) sleep initiation within small neuronal/glial networks, and g) theoretical sleep regulatory models and sleep function theory, e.g., that the preservation of brain plasticity is the primordial sleep function. His current work is focused on sleep- and circadian rhythm-linked brain levels of bacterial cell wall peptidoglycan as a holobiont symbiosis communication pathway.

Matt Layton, MD, PhD research interests include physiological and behavioral aspects of substance use disorders and their treatment, including hyperbaric oxygen use in opioid addiction, and the interactions of natural products and drugs. Asthe physician of record for the Sleep and Performance Research Center, and Medical Director for the Program of Excellence in Addictions Research, he studies how substance use and mental disorders impact sleep architecture and sleep-related behaviors, and he is a co-investigator with many other faculty members in the department.

Yool Lee, PhD researches Circadian rhythms as it plays an important role in physiology and disease therapy. Circadian rhythm disruption, such as sleep deprivation, jet lag, and shift work, is known to increase susceptibility to metabolic diseases such as cancer, metabolic syndrome, and diabetes along with neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Understanding the regulatory pathways controlling the circadian clock and how these interact with various disease processes is crucial for the prevention and treatment of clock-associated disorders. Yool Lee, PhD, lab is focused on understanding the biological mechanisms of circadian physiology and applying this knowledge to the molecular and cellular impact of circadian disruptions on tumor heterogeneity, tumor microenvironment, and metastatic progression in human osteosarcoma, melanoma, and brain cancers. The translational application of his work is directed at the treatment of cancer and aging-related pathologies.

Sterling M. McPherson, PhD, is the Director of the Program of Excellence in Addictions Research (PEAR). Within PEAR, he is the Lead Principal Investigator of the Analytics and Psychopharmacology Laboratory (APPL). He is involved in multiple research projects ranging from basic human toxicology via pharmacokinetics to spatial epidemiology to the health economics of new therapeutics. He has led several NIH-funded behavioral pharmacology and therapeutic development focused projects (e.g., Phase I and II trials) on alcohol, opioids, stimulants, and tobacco use disorders. Currently, his area of foci is on the leveraging contingency management in combination with putative pharmacotherapies for alcohol, opioids, alcohol and tobacco combined, and methamphetamine and opioid use combined. Co-addiction is an emerging focus given the high overlap in use patterns, and the need to address use disorders concomitantly given the direct neurobiological behavioral system linkages.

Additionally, he is also working with several companies on advancing technology platforms to improve buprenorphine/naloxone adherence, and naloxone carriage rates and use. He has partnered with seven different industry sponsors to pursue technology-enhanced addiction treatment platforms and advance the commercialization of novel therapeutics. Lastly, he is dedicated to international research with active collaborations across more than seven different countries.

Sleep, and sleep deprivation, induce specific patterns of gene expression.  Lucia Peixoto, PhD, uses genomic approaches to understand fundamental properties of sleep and other neurologic functions such as learning and memory. Her lab demonstrated specific patterns of gene expression, and its epigenetic regulation, in response to sleep deprivation. This work requires a combination of experimental approaches including behavioral paradigms in autism model systems, molecular biology, and the analysis of high-throughput sequence data. The Peixoto Lab also uses genomic and candidate gene approaches to study neurodevelopmental disabilities, in particular Autism Spectrum Disorder (ASD).  They are currently using several models of human genetic disorders with a high prevalence of ASD to study the mechanism by which sleep and development interact in ASD with a focus on epigenetic and transcriptional regulation.

Brieann Satterfield, PhD, aims to understand the complex phenotype-genotype associations between sleep and circadian rhythms, cognition, and health. Her research has shown that at least some inter-individual differences in cognitive impairment due to sleep deprivation can be attributed to genetic differences, which has led to a better understanding of dissociable, differential cognitive effects of sleep deprivation. In a parallel line of research, Satterfield is studying how sleep loss and circadian disruption increase the risk of poor health outcomes such as metabolic syndrome and cancer.

When an organism is infected by a pathogen, defense pathways are rapidly activated by the innate immune system. These defense responses must be tightly controlled to ensure the innate immune response is sufficient to quell the infection but not so overly robust as to cause prolonged inflammation and tissue damage or, in extreme cases, death. It is known that the nervous system interacts with the immune system to regulate the immune response and help maintain immunological homeostasis. Jingru Sun is working to understand the precise mechanisms by which the nervous system regulates innate immunity.  Using the model system C. elegans, her group has discovered multiple neural circuits that regulate the innate immune response to pathogens. They are dissecting these neuroimmune regulatory pathways at molecular and cellular levels to elucidate how neural-immune regulation works.

Szentirmai’s research is focused on how aspects of metabolism impinge on neuronal circuits that are involved in regulating sleep-wake activity. Szentirmai is working to understand how endocrine and metabolic signals from organs such as the liver, the gastrointestinal tract, and adipose tissue communicate with the hypothalamus to control sleep and coordinate metabolism and vigilance. Her laboratory uses a wide range of experimental approaches that include molecular neuroscience, whole animal physiology and behavior.

Hans Van Dongen, PhD, leads a research program focusing on sleep, sleep deprivation, circadian rhythms, and cognitive performance. He has an extensive track record of experimental and theoretical contributions to sleep research. His research portfolio is broad and, over the past two decades, has included two key focus areas: inter-individual differences in cognitive impairment resulting from sleep deprivation, which he has shown to be both trait-like and task-dependent; and mathematical prediction of performance impairment due to fatigue. More recently, he has broadened his focus to include multi-omics inquiries into the mechanisms by which circadian disruption leads to poor long-term health.