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Ralph Lydic

Ralph LydicRalph Lydic
Ph.D., Texas Tech University

Phone (865) 974-3740

Key words: Neurochemistry, states of consciousness, pain, regulation of respiration

Research Interests

My research program aims to help understand the cellular and neurochemical mechanisms regulating states of consciousness and state-dependent changes in physiology.

Research statement

The goals of Lydic's research are elucidating the mechanisms by which sleep, opioids, and volatile anesthetics modulate pain and depress breathing and arousal.  The evolutionary perspective and current data support the view that neurons generating sleep and wakefulness preferentially modulate the ability of opioids, hypnotics, and anesthetics to alter pain, behavioral affect, and states of waking consciousness.

  • Past President, North American Sleep Research Society
  • Julien F. Biebuyck Endowed Professor of Anesthesia, The Pennsylvania State University, College of Medicine
  • Bert La Du Endowed Professor of Anesthesiology, University of Michigan
  • Distinguished Alumni Award, Graduate School of Biomedical Sciences, Texas Tech Univ.
  • Excellence in Research Award, American Society of Anesthesiologists
  • Past Chairman, Advisory Council, National Space Biomedical Research Inst., Houston, TX
  • Past Chairman, Advisory Panel, Institute of Circulatory and Respiratory Health, Canadian Institute of Health
  • 2015- Scientific Advisory Committee, Canadian Sleep & Circadian Network
  • 2016 Collaborative Scholarship and Research Award, University of Tennessee
  • 2016-2019 Visiting Professor, Peoples Liberation Army Hospital, Beijing, China

Grant Applications

  • Sponsor:  National Institute of Drug Abuse (NIDA)
    Title:  Novel Approach to Substance Use Disorders
    Mechanism:  U18
    Status:  Submitted for February 13, 2020 deadline
    Role:  Co-Investigator (10% effort)

  • Sponsor: National Institute of Drug Abuse (NIDA)
    Title: Opioid-Induced Respiratory Depression
    Mechanism: R01
    Status: Submitted for September 5, 2019; Score: 10th percentile
    Awaiting funding decision
    Role: Co-Investigator 

  • Sponsor: National Institute of General Medical Sciences (NIGMS)
    Title: Mechanisms of Normal and impaired Wound Healing
    Mechanism: RM1
    Status: Submitted January 2019. Not funded. Application in revision.
    Role: Lead investigator on team of six.

  • Sponsor: National Institute of Drug Abuse (NIDA)
    Title: Novel Antagonist for Opioid-Induced Respiratory Depression
    Mechanism: R33
    Status: Submitted September 5, 2019 deadline; not funded
    Role: Co-Investigator

  • Sponsor: Defense Applied Research Projects Agency (DARPA)
    Title: Epistatic Genetic Architecture and Therapeutic Candidates for Opioid Response and Toxicity in Drosophila and Humans - the computational search for an antidote to highly potent, synthetic opioids.
    MechanismApplication invited by DARPA
    Status: Fall 2019 Submission
    Role: Co-investigator

  • Sponsor: National Human Genome Research Institute
    Title: Identification of Structural Variation with Novel Methods and Integration of other Genomic Features to Explain the Genetic Basis of Human Diseases
    Mechanism: HG-18-006 R35 
    Status: Fall 2019 Submission
    Role: Sub-Contract for years 4 and 5

  • Sponsor: NIH National Institute on Drug Abuse
    Title: Identification of Structural Variation with Novel Methods and Integration of other Genomic Features to Explain the Genetic Basis of Human Diseases
    Mechanism: PAR-19-223 Avenir Award to NIH National Institute on Drug Abuse
    Status: Fall 2019 Submission
    Role: Sub-Contract for years 4 and 5

Previous Grants

  • Hettich, R. (P.I.) Co-Investigators Blakely-Ruiz, Lydic R., Carley, Baghdoyan, Simpson.  An Integrated Systems Biology Approach to Identify Opioid-Induced Shifts in Function of the Gut Microbiome among Lean and Obese Mice Undergoing Systemic Opioid Treatment.  Oak Ridge National Laboratory: Funded July 30 2018. $197,000.

  • Lydic, R. (P.I.), Baghdoyan, H.A., Campagna, S., Jacobson, D.A. Opiate alteration in brain chemistry of normal and obese mice: A pilot study. Kavli Foundation. Funded through December 2017. Funded $10,000.

  • Lydic, R. (P.I.) Does leptin contribute to alterations in breathing caused by buprenorphine. NeuroNET Pilot Program, October 2014 through September 2015, University of Tennessee, $10,000.

  • Lydic, R. (P.I.) Cholinergic phenotype in murine models of sleep. Heart, Lung, and Blood Institutes of N.I.H. (R01 HL-065272). Competing Renewal Application funded 01 July 2010 through 30 June 2017.  Award total $1,389,268.

Zhang X, Baer AG, Price J, Jones PC, Garcia BJ, Romero J, Cliff A, Mi W, Brown JB, Jacobson DA, Lydic R, Baghdoyan HA. Neurotransmitter networks in mouse prefrontal cortex are reconfigured by isoflurane anesthesia. Journal of Neurophysiology, in press, 2020.

O'Brien, C.B., Baghdoyan H.A., Lydic R. Computer-based multitaper spectrogram program for electroencephalographic data. Journal of Visualized Experiments. (153), e60333, DOI: doi:10.3791/60333 (2019). URL:

Lu Y, Li Y-W, Wang L, Lydic R, Baghdoyan H.A., Shi X-Y, Zhang H. Sleep promotion is useful in preventing postoperative delirium: a systematic review and meta-analysis of randomized clinical trials. Sleep Medicine Reviews(In Press) 2019.

Blakeley-Ruiz, J., McClintock, C., Lydic, R., Baghdoyan, H.A., Choo, J., and Hettich, R. Combining integrated systems-biology approaches with intervention-based experimental design provides a higher-resolution path forward for microbiome research. Behavioral and Brain Sciences,42, E66, 2019. doi:10.1017/S0140525X18002911

McLain JM, Alami WH, Glovak ZT, Cooley CR, Burke SJ, Collier JJ, Baghdoyan HA, Karlstad MD, Lydic, R.  Sleep fragmentation delays wound healing in a mouse model of type 2 diabetes.  SLEEP 41:(11) 1-9, 2018. doi:10.1093/sleep/zsy156. PMID:30107617

Bourdon AK, Spano G, Marshall W, Bellesi M, Tononi G, Serra PA, Baghdoyan HA, Lydic R, Campagna SR, Cirelli, C. Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep. Scientific Reports 8, 11225 (2018) doi:10.1038/s41598-018-29511-6

Angel C, Glovak ZT, Alami W, Mihalko S, Price J, Jiang Y, Baghdoyan HA, Lydic R. Buprenorphine depresses respiratory variability in obese mice with altered leptin signaling. Anesthesiology 128: 984-991,2018. 10.1097/ALN.0000000000002073

Lydic R, Baghdoyan, HA, May, AL. Neurochemistry of anesthetics states. Methods in Enzymology 603: 237-255, 2018. PMID 29673529

Glovak ZT, Mihalko S, Baghdoyan HA, Lydic, R. Leptin status alters buprenorphine induced antinociception in obese mice with dysfunctional leptin receptors. Neuroscience Letters 660: 29-33,2017 PMCID 5651198

Zhang H, Wheat H, Wang P, Jiang S, Baghdoyan HA, Neubig R, Shi X-Y, Lydic R. RGS proteins and Gαi2 modulate sleep, wakefulness, and disruption of sleep/wake states after isoflurane and sevoflurane anesthesia. SLEEP 39: 393-404, 2016. PMID:26564126

Garrity AG, Botta S, Lazar SB, Swor E, Vanini G, Baghdoyan HA, Lydic R. Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in Sprague Dawley rat. Sleep 38: 73-84, 2015.

Filbey W, Sanford D, Koch LG, Britton SL, Baghdoyan HA, Lydic, R. Dexmedetomidine and eszopiclone depress ventilation in obese rats that have features of metabolic syndrome. Sleep 37: 871-880, 2014.

Hambrecht-Wiedbusch V, Mitchell MF, Firn KA, Baghdoyan HA, Lydic R. Benzodiazepine receptor agonists differentially alter acetylcholine levels in rat amygdala. Anesthesia and Analgesia 118:1293-300, 2014.  PMC4054928

Vanini G, Nemanis K, Baghdoyan HA, Lydic R.  GABAergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation. European Journal of Neuroscience 40: 2264-2273, 2014. PMID:24674578

Watson SL, Watson CJ, Baghdoyan HA, Lydic, R.  Adenosine A1 receptors in mouse pontine reticular formation modulate nociception only in the presence of systemic leptin. Neuroscience 275: 531-539, 2014.

Gettys GC, Liu F, Kimlin E, Baghdoyan HA, and Lydic R. Adenosine A1 receptors in mouse pontine reticular formation depress breathing, increase anesthesia recovery time, and decrease acetylcholine release. Anesthesiology 118: 327-336, 2013.  PMCID: PMC3553235

Wathen AB, West ES, Lydic R, Baghdoyan HA.  Olanzapine causes a leptin-dependent increase in acetylcholine release in mouse prefrontal cortex. Sleep 35: 315-323, 2012. PMCID: PMC3274332

Pal D, Walton M, Lipinski B, Lydic R, Koch LG, Britton SL, Mashour GA.  Determination of minimum alveolar concentration for isoflurane and sevoflurane in a rodent model of human metabolic syndrome.  Anesthesia and Analgesia 114: 297-302, 2012. PMCID: PMC3272881

Vanini G, Lydic R, Baghdoyan HA.  GABA-to-ACh ratio in basal forebrain and cerebral cortex varies significantly during sleep.  Sleep 35: 1325-1334, 2012. PMCID: PMC3443758

Vanini G, Wathen BL, Lydic, R, Baghdoyan HA.  Endogenous GABA levels in the pontine reticular formation are greater during wakefulness than during REM sleep. Journal of Neuroscience 31: 2649-2656, 2011. *(Selected for "This week in the Journal) PMCID: PMC3073841

Brummett CM, Hong E, Janda AM, Amodeo FS, Lydic R. Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the analgesia duration by blocking hyperpolarization-activated cation current.  Anesthesiology 115: 836-43, 2011.  PMCID: PMC3179561

Gauthier EA, Guzick SE, Brummett CM, Baghdoyan HA, Lydic R.  Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep-regulating brain regions of Sprague Dawley rat. Anesthesiology 115: 743-53 2011.  PMCID: PMC5197808

Watson CJ, Lydic, R, Baghdoyan HA. Glutamate and GABA in rat pontine reticular formation modulate sleep duration.  Journal of Neurochemistry 118: 571-80, 2011. PMCID: PMC3144159

Watson SL, Watson CJ, Baghdoyan HA, Lydic R. Thermal nociception is decreased by hypocretin-1 and an adenosine A1 receptor agonist microinjected into the pontine reticular formation of Sprague Dawley rat.  Journal of Pain 11: 535-544, 2010. PMCID: PMC2879477

Brown E, Lydic R, Schiff ND.  General anesthesia, sleep, and coma.  New England Journal of Medicine 363: 2638-2650, 2010.  PMID: 21190458

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