Room: (VBR) 313
2012-Present Associate Professor, IPN, College of Veterinary Medicine, Washington State University, Pullman, WA
2016-Present Associate Director of Graduate Studies, IPN, College of Veterinary Medicine, Washington State University, Pullman, WA
Why in a neighborhood exposed to the same levels of environmental toxins, do a handful of people develop health problems, while others seem unaffected? Why are some individuals able to eat high-fat, high-calorie diets without developing high cholesterol and hypertension, even though they don’t exercise more? Why in two individuals who experience the same exposure to a traumatic event does only one manifest symptoms of Post-Traumatic Stress Disorder? While many were hoping differences in genotype would be the answer to such questions, we are now more aware that interactions between genes, development, and experience shape an individual’s response to events in the environment. Some individuals show remarkable resilience while others show significant vulnerability to environmental challenges, and the differences in outcome between these groups could not more stark. The physiological and cellular mechanisms of resilience and vulnerability are unknown, but their discovery will change how physical and mental illnesses are treated, potentially preventing negative health effects before they occur by enabling us to predict individuals’ responses, and permitting deployment of countermeasures to mitigate negative outcomes. A goal of my lab is to help uncover these mechanisms, and while we use rodent models in our work, they have direct relevance to human physiology and health.
My lab investigates how organisms interact with their environments, and the mechanisms by which the environment shapes physiological and neurobehavioral function to drive adaptation. Maintaining optimal physiologic function requires organisms to accomplish at least two tasks: 1) anticipate recurring changes in the environment, and 2) adapt to unexpected environmental challenges. The circadian (daily) timing system is essential to the former, relying on cues in the environment to anticipate recurring environmental changes. On the other hand, the stress response system is essential for perceiving, responding to, and recovering from unexpected events. These systems are important because their disruption is linked to significant negative impacts on metabolic, immune, and neurobehavioral function. We employ the circadian and stress systems as models to probe how physiological dysregulation leads to long-term negative health consequences, using integrative, multi-level approaches.
We have two major research questions:
1) How do normal circadian rhythms and sleep promote health, and how do disrupted rhythms increase vulnerability?
2) How does disruption of the brain-body stress axis alter long-term vulnerability and resilience?
We use transgenic mouse models, behavioral and metabolic assays, and sleep electrophysiology, along with analyses of neural structure/function through gene expression, confocal microscopy, and 3-D cellular reconstructions. My lab can measure metabolic activity of brain tissue using implanted biosensors in awake behaving rodents, and employs assays of immune function to probe environment-brain-body interactions. We aim to understand the functional integration of multiple organ systems, and determine the mechanisms by which homeostasis is maintained, how adaptations are made when homeostasis is challenged, and the long term consequences of failures to adapt.
A major guiding principle of our research program is the concept of allostasis, or the maintenance of stability through active intervention. The physiological mediators of allostasis include sympathetic/parasympathetic activation, metabolic hormones, pro- and anti-inflammatory cytokines, and glucocorticoids (see figure, above). These mediators engage central and peripheral adaptations in order to overcome the short-term increase in environmental demands (i.e. the stressor), and are actively regulated to restore normal homeostasis. The concept of allostasis should not be considered as a replacement for the term “stress”, but is meant to emphasize that the responses engaged when a threat to homeostasis is detected are not in and of themselves negative, but essential adaptive responses. It is only when these responses are inappropriately engaged, improperly terminated, or become chronic that they result in negative health consequences.
2001 B.Sc. Psychology; University of Toronto, Canada
2004 M.A. Psychology, Columbia University, NY
2008 Ph.D. Psychology; Columbia University, NY
Postdoctoral Fellowship: Laboratory of Neuroendocrinology; The Rockefeller University, NY
Honors and Awards
2006 Young Investigator Award, Society for Behavioral Neuroendocrinology
2016 Dean's Outstanding Junior Faculty Research Award
Prior Academic Appointments
2010-2011 Adjunct Assistant Professor, Columbia University
2007-2012 Postdoctoral Fellow, The Rockefeller University
NSF CAREER Biological Timing and Brain Circuits: Circadian influences on Prefrontal Cortex function, PI
NIH Environmentally driven metabolic dysregulation as a model of accelerated aging, PI
- Karatsoreos IN (2012) Effects of circadian disruption on mental and physical health Curr Neurol Neurosci Rep 12(2), 218-25 PMID: 22322663
- Karatsoreos IN, McEwen BS (2011) Psychobiological allostasis: resistance, resilience and vulnerability Trends Cogn Sci 15(12), 576-84 PMID: 22078931
- Karatsoreos IN, Thaler JP, Borgland SL, Champagne FA, Hurd YL, Hill MN (2013) Food for thought: hormonal, experiential, and neural influences on feeding and obesity J Neurosci 33(45), 17610-6 PMID: 24198352 PMCID: PMC3818543
- Romeo RD, Minhas S, Svirsky SE, Hall BS, Savenkova M, Karatsoreos IN (2014) Pubertal shifts in adrenal responsiveness to stress and adrenocorticotropic hormone in male rats Psychoneuroendocrinology 42, 146-52 PMID: 24636511 PMCID: PMC3959666
- Karatsoreos IN (2014) Links between Circadian Rhythms and Psychiatric Disease Front Behav Neurosci 8, 162 PMID: 24834040 PMCID: PMC4018537
- Phillips DJ, Savenkova MI, Karatsoreos IN (2015) Environmental disruption of the circadian clock leads to altered sleep and immune responses in mouse Brain Behav Immun 47, 14-23 PMID: 25542734
- Kinlein SA, Wilson CD, Karatsoreos IN (2015) Dysregulated hypothalamic-pituitary-adrenal axis function contributes to altered endocrine and neurobehavioral responses to acute stress Front Psychiatry 6, 31 PMID: 25821436 PMCID: PMC4358064
- McEwen BS, Bowles NP, Gray JD, Hill MN, Hunter RG, Karatsoreos IN, Nasca C (2015) Mechanisms of stress in the brain Nat Neurosci 18(10), 1353-63 PMID: 26404710 PMCID: PMC4933289
- Kaplowitz ET, Savenkova M, Karatsoreos IN, Romeo RD (2016) Somatic and Neuroendocrine Changes in Response to Chronic Corticosterone Exposure During Adolescence in Male and Female Rats J Neuroendocrinol 28(2), 12336 PMID: 26568535
- Karatsoreos IN (2016) The Complexity of Simplicity: Role of Sex, Development and Environment in the Modulation of the Stress Response J Neuroendocrinol 28(8) PMID: 27005563 PMCID: PMC5007192