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James M. Krueger, Ph.D.

Education
Ph.D. in physiology, University of Pennsylvania, Philadelphia

Bachelor of Science, University of Wisconsin, Madison

Honorary Degrees
Doctorem Medicinae Honoris Causa, University of Szeged, Hungary

Fellowships
NIH Fellowship, the Institute of Neurological Sciences, University of Pennsylvania

Teaching
Dr. James M. Krueger has taught at the University of Wisconsin, University of Pennsylvania, Harvard Medical School, the University of Health Sciences/Chicago Medical School and the University of Tennessee Medical School. At Washington State University he has taught several topics including neurophysiology, cellular and molecular neurobiology, biological rhythms, and sleep.

Krueger has mentored medical and graduate students, and trained postdoctoral fellows, at the Chicago Medical School, the University of Tennessee, and Washington State University. He currently has 3 students working with him in his sleep lab.

Sleep Research
Krueger focuses on the biochemical regulation of sleep. He has described the somnogenic actions of many cytokines, and showed that interleukin-1 and tumor necrosis factor are involved in physiological sleep regulation. Further, Krueger’s lab has an independent project demonstrating the involvement of growth hormone releasing hormone in sleep regulation. For each of these substances he showed that their mRNA and protein levels vary in the brain with the sleep-wake cycle and are affected by sleep deprivation. He has shown that these substances increase non-rapid eye movement sleep (NREMS). Conversely, if they are inhibited sleep is inhibited and the sleep rebound after sleep deprivation is also blocked. Mice lacking IL1 or TNF receptors, and animals under-expressing GHRH or the GHRH receptor, sleep less than normal. Krueger has also examined many substances related to these somnogens with the goal of developing our knowledge of the biochemical network regulating sleep.

Krueger’s second research interest deals with sleep and infectious diseases. Bacterial, protozoan, fungal, and viral infectious agents greatly alter sleep. In the case of bacteria, he determined the molecular steps responsible. For example, with gram-positive bacteria, bacterial peptidoglycan (from cell walls) is digested by macrophages, releasing somnogenic muramyl peptides (these are the monomeric building blocks of bacterial cell walls). Muramyl peptides in turn induce enhanced production of cytokines which in turn affect sleep. Currently, Krueger’s lab is focused on the mechanisms involved in influenza virus induced sleep. In this case, viral double-stranded RNA, released from infected cells, seems responsible for initiating the sleep cascade.

A third interest is with sleep function and brain organization as it applies to sleep. Krueger has hypothesized that neuronal groups are the organizational level at which sleep is initiated. Much recent experimental data support this idea. He is currently testing the hypothesis that sleep serves a synaptic plasticity function by examination of molecular events associated with synaptic reorganization and whether sleep affects those events. For example, individual cortical columns such as somatosensory barrels alternate between functional states, one of which is usually associated with organism sleep and which is induced by TNF. Rats given a whisker cut on one side of the face change several molecular markers of synaptic plasticity in the contralateral somatosensory cortex, e.g. GAD 67, and NGF. The direction of the change was dependent upon the nature of the ongoing synaptic reorganization.

Additional Information
Krueger received his Bachelor of Science from the University of Wisconsin, his doctorate in physiology from the University of Pennsylvania, and his Doctorem Medicinae Honoris Causa from the University of Szeged. From 1974-78 he served as a research fellow and then an instructor in the Harvard Medical School Department of Physiology, and from 1978-81 he was a research associate in the same department. In 1981, he joined the Chicago Medical School Department of Physiology and Biophysics. He worked as an associate and full professor from 1985-97 at the Department of Physiology and Biophysics at the University of Tennessee. He joined VCAPP in 1997, and in 2007 was named a WSU Regents Professor. In 2010, Krueger received designation as Eminent Professor, the highest award given to WSU faculty. In 2012, he was named the WSU Honors College Faculty Thesis Advisor of the Year, and elected to the Washington State Academy of Sciences.

Honors and Awards:
2012 - Washington State Academy of Sciences (elected 2012)
2012 - Honors College Faculty Thesis Advisor of the Year, Washington State University
2010 - Eminent Faculty Award, Washington State University
2006 - Pfizer Lectureship in Sleep, University of Michigan
2006 - Distinguished Scientist Award, Sleep Research Society
2005 - Doctorem Medicinae Honoris Causa, University of Szeged, Hungary
2003 - Pfizer Award for Research Excellence, Washington State University College of Veterinary Medicine
2001 - Sahlin Faculty Excellence Award for Research, Washington State University
2000 - Neuroscience Grass Traveling Scientist, Jackson, Mississippi
1999 - Visiting Professor, Nanjing Medical University, Jiangsu Province, China
1997-2004 - NIH/NINDS: Javits Award
1995-1996 - President of Faculty Senate, University of Tennessee-Memphis
1990 - Honorary Award, Tokyo Medical and Dental University, Japan
1983 - Board of Trustees Research Award, Chicago Medical School
1978-1979 - American Heart Association Career Investigator Fellow

Patents:

• Sleep Promoting Factor: issued August 3, 1982 [#4,342,748]
• Somnogenic Compositions and Method of Use: issued May 26, 1987 [#4,668,661]
• Interleukin-1 Fragment - Method of Inducing Sleep: issued December 24, 1991 [#5075288]
• Complementary Peptides - Method of Inducing Sleep With GHRH Complementary Peptide Compositions: issued October 6, 1992 [#5153175]
• Administering Bacteria to Improve Sleep: issued September 23, 2002 (#6,444,203 B2)
• Method for reduction in caloric intake; GHRELIN siRNA administration. Application No. 12/700,009; filed 02/04/2010; issued Oct 2012

Selected Publications (from a total of 377)
Peterfi Z, Makara GB, Obal Jr F, Krueger JM (2009) The anterolateral projections of the medial basal hypothalamus affect sleep. Am. J. Physiol. 296:R1228-R1238. PMCID: PMC2698612

Rector DM, Schei JL, Van Dongen HPA, Belenky G, Krueger JM. (2009) Physiological markers of localized sleep. Europ. J. Neurosci. 29:1771-1778. PMCID: PMC2688439

Leyva-Grado V, Churchill L, Wu M, Williams, TJ, Taishi P, Majde JA, Krueger JM. (2009) Influenza virus- and cytokine-immunoreactive cells in the murine olfactory pathway and hypothalamus before and after illness onset. J. Neuroimmunol. 211:73-83. PMCID: PMC2696569

May U, Schiffelholz T, Baier PC, Krueger JM, Rose-John S, Scheller J. (2009) IL-6 trans-signalling increases rapid eye-movement sleep in rats. European. J. Pharmacology 613:141-145. PMID: 19383498

Szentirmai , Kaps L, Sun Y, Smith RG, Krueger JM. (2009) The preproghrelin gene is required for normal integration of thermoregulation and sleep in mice. Proc. Natl. Acad. Sci. USA 106: 14069-14074.

Leyva-Grado V, Churchill L, Harding J, Krueger JM (2010) The olfactory nerve has a role in the body temperature and brain cytokine responses to influenza virus. Brain Beh. Immun. 24: 281-288. PMCID: PMC2729021

Liao F, Taishi P, Churchill L, Urza JM, Krueger JM (2010) Localized suppression of cortical growth hormone releasing hormone receptors state-specifically attenuates EEG delta waves. J. Neurosci. 30:4151-4159. PMCID: PMC2846621

Hallett H, Churchill L, Taishi P, De A, Krueger JM (2010) Whisker stimulation increases expression of nerve growth factor and interleukin-1 beta immunoreactivity in the rat somatosensory cortex. Brain Res. 1333: 48-56. PMCID: PMC2879054

Krueger JM, Taishi P, De A, Davis C, Winters BD, Clinton J, Szentirmai E, Zielinski MR. (2010) ATP and the purine type 2 X7 receptor affect sleep. J Appl Physiol. 109:1318-1327. PMCID: PMC2980381

Krueger JM, Wisor JP. (2011) Local use-dependent sleep; an introduction. Current Topics in Medicinal Chemistry 11:2390-2391. PMCID: PMC3243827

Krueger JM, Tononi G. (2011) Local use-dependent sleep; synthesis of the new paradigm. Current Topics in Medicinal Chemistry 11:2490-2492.360. PMCID: PMC3248786

Gardi J, Nelson OL, Robbins CT, Szentirmai E, Kapas L, Krueger JM. (2011) Energy homeostasis regulatory peptides in hibernating grizzly bears. Gen. and Comp. Endocrinology 172:181-183. PMCID: PMC3263427

Davis, CJ, Clinton JM, Taishi P, Bohnet SG, Honn, KA, Krueger, JM. (2011) MicroRNA 132 alters sleep and varies with time in brain. J Appl. Physiol. 111:665-672. PMCID: PMC3174793

Hodgson NR, Bohnet SG, Majde JA, Krueger JM. Influenza virus pathophysiology and brain invasion in mice with functional and dysfunctional Mx1 genes. (2012) Brain, Behav. Immunity 26:83-89. PMCID: PMC3221813

Winters BD, Huang Y, Dong Y, Krueger JM. (2011) Sleep loss alters synaptic and intrinsic neuronal properties in mouse prefrontal cortex. Brain Res 1420:1-7. PMCID: PMC3205322

Taishi P, Davis CJ, Bayomy O, Zielinski MR, Liao F, Clinton JM, Smith DE, Krueger JM. Brain –specific interleukin-1 receptor accessory protein in sleep regulation. (2012) J. Appl. Physiol. 112:1015-1022. PMID: 22174404; PMCID: in process.

Zielinski M, Taishi P, Clinton JM, Krueger JM. (2012) 5’-ectonucleotidase knockout mice lack non-REM sleep responses to sleep deprivation. Europ. J. Neurosci. 35:1789-1798. PMCID: not yet assigned. PMID: 22540145.

Winters BD, Kruger JM, Huang X, Gallaher ZR, Ishikawa M, Czaja, K, Krueger JM, Huang YH, Schluter OM, Dong Y. (2012) CB1-expressing neurons in the nucleus accumbens. Proc. Natl. Acad. Sci. 109:E2717-E2725. PMID: 23012412.

Davis, CJ, Clinton JM, Krueger JM. (2012) MicroRNAs 138, let7b and 125a inhibitors differentially alter sleep and EEG delta wave activity in rats. J. Appl. Physiol. (in press).

Zielinski MR, Dunbrasky DL, Taishi P, Souza G, Krueger JM. Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor alpha and lipopolysaccharide in mice. Sleep (in press).

More publications [PubMed]
All publications [.pdf]

In the News
Professor here looks for link between sleep, recovery, Journal of Business, October 25, 2012

Sleep Switch Found in the Brain, Discover Magazine's Top 100 Stories of 2010

Tripping on the Edge of Consciousness, by Jim Krueger, second in The Human Side of Science series.

The Secrets of Sweet Oblivion, Washington State Magazine

Eat, Sleep, Stay Warm: How our bodies find the right balance, August 12, 2009, WSU Today Online (with a link to the National Academy of Science Proceeding)

Why do we sleep? - WSU Research Feature

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