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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
  • 2020 University of Tennessee, Department of Psychology, Undergraduate Student Mentoring Award
  • 2020 Chair, NASA Postdoctoral Review Committee Translational Research Institute for Space Health

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.

Scott HL , Bolmatov H, Podar PT, Zening L, Kinnun JJ, Doughty B, Lydic R, Sacci RL, Collier CP, and Katsaras J. Evidence for long-term potentiation in phospholipid membranes. PNAS 119: (50) e2212195119 2022.

Glovak ZT, Baghdoyan HA, Lydic R.  Fentanyl and neostigmine delivered to mouse prefrontal cortex differentially alter breathing. Respiratory Physiology and Neurobiology 303: 110 2022. PMID:35662641

Blakely-Ruiz JA, McClintock CS, Shrestha HK, Poudel S, Yang ZK, Giannone RJ, Choo JJ, Podar M, Baghdoyan HA, Lydic R, Hettich RL. Morphine and high-fat diet differentially alter the gut microbiota composition and metabolic function in lean versus obese mice.  ISME COMMUN. 2, 66 2022.

Glovak ZT, Angel C, O'Brien CB, Baghdoyan HA, and Lydic R. Buprenorphine differentially alters breathing among four congenic mouse lines as a function of dose, sex, and leptin status. Respir Physiol Neurobiol, Online ahead of print: PMID: 34954128 DOI:10.1016/j.resp.2021.103834

O’Brien CB, Locklear CE, Glovak ZT, Zebadúa Unzaga D, Baghdoyan HA, Lydic R. Opioids cause dissociated states of consciousness in C57BL/6J mice. Journal of Neurophysiology 126: 1265-1275, 2021

Lydic R and Baghdoyan HA. Prefrontal cortex metabolome is modified by opioids, anesthesia, and sleep. Physiology 36: 203-219, 2021.

Ramirez J-M, Burgraff N, Wei A, Baertsch, N, Varga A, Saunders S, Baghdoyan HA, Lydic R, Morris, R, Bolser D, Levitt E.  Neuronal mechanisms underlying opioid Induced respiratory depression. Journal of Neurophysiology 125: 1899-1919, 2021.

Baer AG, Bourdon AK, Price JM, Campagna SR, Jacobson DA, Baghdoyan HA, Lydic R. Isoflurane anesthesia disrupts the cortical metabolome. Journal of Neurophysiology 124: 2012-2021, 2020.

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 123: 2285-2296, 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 HA, Shi X-Y, Zhang H. Promoting sleep and circadian health may prevent postoperative delirium: A systematic review and meta-analysis of randomized clinical trials. Sleep Medicine Reviews 48:101207, 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

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