Angela R. Ozburn, Ph.D.

  • Associate Professor of Behavioral Neuroscience, School of Medicine
  • Behavioral Neuroscience Graduate Program, School of Medicine

Biography

About

Research in my laboratory is directed toward a better understanding of the molecular mechanisms that underlie addiction and improved treatment of substance use disorders.

Significance

Substance use disorders have a devastating impact on individuals and their families, with substantial medical and societal impact. Alcoholism is associated with disruptions in circadian rhythms that persist during abstinence and increase risk for relapse. Additionally, genetic variations (SNPs or mutations) in circadian genes have been shown to modulate alcohol consumption, anxiety, depression, and mania in humans. Pre-clinical studies have also revealed that circadian mutations in homologous circadian transcription factors, CLOCK and NPAS2, can alter drug sensitivity and mood-related behaviors. We carry out studies to directly address how brain region and cell specific expression of these genes affects mood- and drug-related behaviors. Findings from these studies will have important translational significance by contributing to our understanding of vulnerability for substance use disorders and susceptibility to relapse.

Substance use disorders are characterized by inability to control intake and high rates of relapse. There exists a serious public health need to identify and characterize new and more effective treatments. Therapies that increase neuronal activity in the nucleus accumbens (NAc) are emerging as a promising treatment tool for alcohol use disorders. However, further research is needed to determine behavioral and molecular consequences of increasing specific brain activity. I am addressing this gap in our knowledge by using genetic and pharmacological approaches to determine the effects of chronic NAc stimulation on the rewarding and aversive aspects of alcohol behaviors, as well as identify treatment responsive gene networks and specific circuitry that underlie lasting reductions in alcohol intake. Findings will provide a great deal of insight into mechanisms underlying the effectiveness of new potential therapies for alcohol use disorders.

Goals

My long-term career goals are to move science forward by contributing to the understanding of the molecular mechanisms that underlie addiction and to improved treatment of substance use disorders. Despite advances in neuroscience and psychiatry, we have much to gain in our understanding of substance use disorders and the development of more effective treatments. My specific goals are to: 1) identify mechanisms mediating circadian gene effects on drug- and mood-related behaviors, and 2) identify how altering specific brain activity can alter alcohol-related behaviors and identify transcriptional mechanisms that underlie lasting reductions in binge-like drinking.

Approaches

I am currently using several complementary approaches in mice to carry out the above research goals: a) clinically relevant drug self-administration models (operant drug self-administration and binge-drinking paradigms), b) viral-mediated gene transfer to temporally and spatially control gene expression and neuronal activity (using DesignerReceptors Exclusively Activated by Designer Drugs, DREADDs), c) behavioral battery of drug and mood-related assays, and d) identification of transcriptional mechanisms and the regulation of gene expression using RNA and ChIP Seq, qPCR, and Western blotting.  

Education and training

  • Degrees

    • Ph.D., 2009, University of Texas

Areas of interest

  • Circadian gene regulation of mood- and alcohol-use disorders
  • Testing and characterizing therapies for reducing alcohol and drug intake in animal models

Additional information

Publications

Selected publications

  • Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice.Purohit K, Parekh PK, Kern J, Logan RW, Liu Z, Huang Y, McClung CA, Crabbe JC, Ozburn AR.Alcohol Clin Exp Res. 2018 May;42(5):879-888. doi: 10.1111/acer.13626. Epub 2018 Apr 18.PMID: 29668112.
  • Genome-Wide Expression Profiles Drive Discovery of Novel Compounds that Reduce Binge Drinking in Mice.Ferguson LB, Ozburn AR, Ponomarev I, Metten P, Reilly M, Crabbe JC, Harris RA, Mayfield RD.Neuropsychopharmacology. 2018 May;43(6):1257-1266. doi: 10.1038/npp.2017.301. Epub 2017 Dec 18.PMID: 29251283.
  • NPAS2 Regulation of Anxiety-Like Behavior and GABAA Receptors.Ozburn AR, Kern J, Parekh PK, Logan RW, Liu Z, Falcon E, Becker-Krail D, Purohit K, Edgar NM, Huang Y, McClung CA.Front Mol Neurosci. 2017 Nov 3;10:360. doi: 10.3389/fnmol.2017.00360. eCollection 2017.PMID: 29163035.
  • High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking.Crabbe JC, Ozburn AR, Metten P, Barkley-Levenson A, Schlumbohm JP, Spence SE, Hack WR, Huang LC.Pharmacol Biochem Behav. 2017 Sep;160:55-62. doi: 10.1016/j.pbb.2017.08.002. Epub 2017 Aug 5.PMID: 28827047.
  • Functional Implications of the CLOCK 3111T/C Single-Nucleotide Polymorphism.Ozburn AR, Purohit K, Parekh PK, Kaplan GN, Falcon E, Mukherjee S, Cates HM, McClung CA.Front Psychiatry. 2016 Apr 21;7:67. doi: 10.3389/fpsyt.2016.00067. eCollection 2016.PMID: 27148095.
  • Commonalities and Distinctions Among Mechanisms of Addiction to Alcohol and Other Drugs.Ozburn AR, Janowsky AJ, Crabbe JC.Alcohol Clin Exp Res. 2015 Oct;39(10):1863-77. doi: 10.1111/acer.12810. Review.PMID: 26431116.
  • Circadian clock genes: effects on dopamine, reward and addiction.Parekh PK, Ozburn AR, McClung CA.Alcohol. 2015 Jun;49(4):341-9. doi: 10.1016/j.alcohol.2014.09.034. Epub 2015 Jan 8. Review.PMID: 25641765.
  • Direct regulation of diurnal Drd3 expression and cocaine reward by NPAS2.Ozburn AR, Falcon E, Twaddle A, Nugent AL, Gillman AG, Spencer SM, Arey RN, Mukherjee S, Lyons-Weiler J, Self DW, McClung CA.Biol Psychiatry. 2015 Mar 1;77(5):425-433. doi: 10.1016/j.biopsych.2014.07.030. Epub 2014 Aug 13.PMID: 25444159.
  • Differential regulation of the period genes in striatal regions following cocaine exposure.Falcon E, Ozburn A, Mukherjee S, Roybal K, McClung CA.PLoS One. 2013 Jun 11;8(6):e66438. doi: 10.1371/journal.pone.0066438. Print 2013.PMID: 23776671.
  • The role of clock in ethanol-related behaviors.Ozburn AR, Falcon E, Mukherjee S, Gillman A, Arey R, Spencer S, McClung CA.Neuropsychopharmacology. 2013 Nov;38(12):2393-400. doi: 10.1038/npp.2013.138. Epub 2013 May 31.PMID: 23722243.

Publications

  • Codeveloping and Implementing an Indigenous Mentoring Program for Native American Faculty in Science, Technology, Engineering, and Mathematics

    Journal of Diversity in Higher Education
    1. Maja Pedersen
    2. Anne Des Rosier Grant
    3. Jennifer Harrington
    4. Annie Belcourt
    5. Aaron Thomas
    6. Serra Hoagland
    7. Jordan P. Lewis
    8. Ruth Plenty Sweetgrass She Kills
    9. Otakuye Conroy-Ben
    10. Eric Brodt
    11. Karletta Chief
    12. Michelle Johnson-Jennings
    13. Kirsten Green Mink
    14. Kathryn Milligan-McClellan
    15. Matt Calhoun
    16. Angela Ozburn
    17. Vanessa Simonds
    18. Stephan Chase
    19. Ranalda Tsosie
    20. Ke We
    21. Blakely Brown

  • Effects of metformin on binge-like ethanol drinking and adenosine monophosphate kinase signaling in inbred high drinking in the dark line 1 mice

    Alcohol, Clinical and Experimental Research
    1. Kolter Grigsby
    2. Jonathan Palacios
    3. Amy E. Chan
    4. Sade M. Spencer
    5. Angela R. Ozburn

  • Repurposing anti-inflammatory medications for alcohol and substance use disorders

    Neuropsychopharmacology
    1. Angela R. Ozburn
    2. Sade M. Spencer

  • Development and implementation of a Dependable, Simple, and Cost-effective (DSC), open-source running wheel in High Drinking in the Dark and Heterogeneous Stock/Northport mice

    Frontiers in Behavioral Neuroscience
    1. Kolter Grigsby
    2. Zaynah Usmani
    3. Justin Anderson
    4. Angela Ozburn

  • Preclinical and clinical evidence for suppression of alcohol intake by apremilast

    Journal of Clinical Investigation
    1. Kolter B. Grigsby
    2. Regina A. Mangieri
    3. Amanda J. Roberts
    4. Marcelo F. Lopez
    5. Evan J. Firsick
    6. Kayla G. Townsley
    7. Alan Beneze
    8. Jessica Bess
    9. Toby K. Eisenstein
    10. Joseph J. Meissler
    11. John M. Light
    12. Jenny Miller
    13. Susan Quello
    14. Farhad Shadan
    15. Michael Skinner
    16. Heather C. Aziz
    17. Pamela Metten
    18. Richard A. Morrisett
    19. John C. Crabbe
    20. Marisa Roberto
    21. Howard C. Becker
    22. Barbara J. Mason
    23. Angela R. Ozburn

  • Brain gene expression differences related to ethanol preference in the collaborative cross founder strains

    Frontiers in Behavioral Neuroscience
    1. Justin Q. Anderson
    2. Priscila Darakjian
    3. Robert Hitzemann
    4. Denesa R. Lockwood
    5. Tamara J. Phillips
    6. Angela R. Ozburn

  • Central nucleus of the amygdala projections onto the nucleus accumbens core regulate binge-like alcohol drinking in a CRF-dependent manner

    Neuropharmacology
    1. Marissa B. Borrego
    2. Kolter B. Grigsby
    3. Kayla G. Townsley
    4. Amy Chan
    5. Evan J. Firsick
    6. Alex Tran
    7. Antonia Savarese
    8. Angela R. Ozburn

  • Corticosterone Levels and Glucocorticoid Receptor Gene Expression in High Drinking in the Dark Mice and Their Heterogeneous Stock (HS/NPT) Founder Line

    Frontiers in Behavioral Neuroscience
    1. Antonia M. Savarese
    2. Kolter B. Grigsby
    3. Bryan E. Jensen
    4. Marissa B. Borrego
    5. Deborah A. Finn
    6. John C. Crabbe
    7. Angela R. Ozburn

  • Exploring Personal, Relational, and Collective Experiences and Mentorship Connections That Enhance or Inhibit Professional Development and Career Advancement of Native American Faculty in STEM Fields

    Journal of Diversity in Higher Education
    1. Blakely Brown
    2. Maja Pedersen
    3. Jennifer Harrington
    4. Annie Belcourt
    5. Sweeney Windchief
    6. Aaron Thomas
    7. Ruth Plenty Sweetgrass She Kills
    8. Otakuye Conroy-Ben
    9. Erik Brodt
    10. Karletta Chief
    11. Serra Hoagland
    12. Michelle Johnson-Jennings
    13. Jordan Lewis
    14. Kirsten Green Mink
    15. Kathryn C.A. Milligan-Myhre
    16. Matthew Calhoun
    17. Angela Ozburn
    18. Vanessa Simonds
    19. Anne Des Rosier Grant
    20. Salena Hill
    21. Ke Wu

  • Long-term alcohol drinking in High Drinking in the Dark mice is stable for many months and does not show alcohol deprivation effects

    Addiction Biology
    1. John C. Crabbe
    2. Wyatt R. Hack
    3. Angela R. Ozburn
    4. Antonia M. Savarese
    5. Pamela Metten

  • Midazolam, methamphetamine, morphine and nicotine intake in high-drinking-in-the-dark mice

    Addiction Biology
    1. Antonia M. Savarese
    2. Pamela Metten
    3. Tamara J. Phillips
    4. Bryan E. Jensen
    5. John C. Crabbe
    6. Angela R. Ozburn

  • Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression

    International journal of molecular sciences
    1. Kolter Grigsby
    2. Courtney Ledford
    3. Tanvi Batish
    4. Snigdha Kanadibhotla
    5. Delaney Smith
    6. Evan Firsick
    7. Alexander Tran
    8. Kayla Townsley
    9. Kaylee Abril Vasquez Reyes
    10. Katherine LeBlanc
    11. Angela Ozburn

  • Effects of chemogenetic manipulation of the nucleus accumbens core in male C57BL/6J mice

    Alcohol
    1. Kayla G. Townsley
    2. Marissa B. Borrego
    3. Angela R. Ozburn

  • Ethanol-related behaviors in mouse lines selectively bred for drinking to intoxication

    Brain Sciences
    1. Bryan E. Jensen
    2. Kayla G. Townsley
    3. Kolter B. Grigsby
    4. Pamela Metten
    5. Meher Chand
    6. Miracle Uzoekwe
    7. Alex Tran
    8. Evan Firsick
    9. Katherine Leblanc
    10. John C. Crabbe
    11. Angela R. Ozburn

  • The impact of Drinking in the Dark (DID) procedural manipulations on ethanol intake in High Drinking in the Dark (HDID) mice

    Alcohol
    1. Antonia M. Savarese
    2. Angela R. Ozburn
    3. Amanda M. Barkley-Levenson
    4. Pamela Metten
    5. John C. Crabbe

  • Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2

    Molecular Psychiatry
    1. Ryan W. Logan
    2. Angela R. Ozburn
    3. Rachel N. Arey
    4. Kyle D. Ketchesin
    5. Alicia Winquist
    6. Andrew Crain
    7. Brian T.D. Tobe
    8. Darius Becker-Krail
    9. Matthew B. Jarpe
    10. Xiangning Xue
    11. Wei Zong
    12. Zhiguang Huo
    13. Puja K. Parekh
    14. Xiyu Zhu
    15. Ethan Fitzgerald
    16. Hui Zhang
    17. Jeffrey Oliver-Smith
    18. Lauren M. DePoy
    19. Mariah A. Hildebrand
    20. Evan Y. Snyder
    21. George C. Tseng
    22. Colleen A. McClung

  • Chronic chemogenetic stimulation of the nucleus accumbens produces lasting reductions in binge drinking and ameliorates alcohol-related morphological and transcriptional changes

    Brain Sciences
    1. Dar’Ya Y. Pozhidayeva
    2. Sean P. Farris
    3. Calla M. Goeke
    4. Evan J. Firsick
    5. Kayla G. Townsley
    6. Marina Guizzetti
    7. Angela R. Ozburn

  • Effects of Pharmacologically Targeting Neuroimmune Pathways on Alcohol Drinking in Mice Selectively Bred to Drink to Intoxication

    Alcoholism: Clinical and Experimental Research
    1. Angela R. Ozburn
    2. Pamela Metten
    3. Sheena Potretzke
    4. Kayla G. Townsley
    5. Yuri A. Blednov
    6. John C. Crabbe

  • Effects of Tacrolimus and Other Immune Targeting Compounds on Binge-Like Ethanol Drinking in High Drinking in the Dark Mice

    Neuroscience Insights
    1. Kolter B. Grigsby
    2. Antonia M. Savarese
    3. Pamela Metten
    4. Barbara J. Mason
    5. Yuri A. Blednov
    6. John C. Crabbe
    7. Angela R. Ozburn

  • Targeting the Glucocorticoid Receptor Reduces Binge-Like Drinking in High Drinking in the Dark (HDID-1) Mice

    Alcoholism: Clinical and Experimental Research
    1. Antonia M. Savarese
    2. Angela R. Ozburn
    3. Pamela Metten
    4. Jason P. Schlumbohm
    5. Wyatt R. Hack
    6. Kathryn LeMoine
    7. Hazel Hunt
    8. Felix Hausch
    9. Michael Bauder
    10. John C. Crabbe

  • Tetracycline derivatives reduce binge alcohol consumption in High Drinking in the Dark mice

    Brain, Behavior, and Immunity - Health
    1. John C. Crabbe
    2. Angela R. Ozburn
    3. Robert J. Hitzemann
    4. Stephanie E. Spence
    5. Wyatt R. Hack
    6. Jason P. Schlumbohm
    7. Pamela Metten

  • Ethanol conditioned taste aversion in high drinking in the dark mice

    Brain Sciences
    1. John C. Crabbe
    2. Pamela Metten
    3. Antonia M. Savarese
    4. Angela R. Ozburn
    5. Jason P. Schlumbohm
    6. Stephanie E. Spence
    7. Wyatt R. Hack

  • Genome-Wide Expression Profiles Drive Discovery of Novel Compounds that Reduce Binge Drinking in Mice

    Neuropsychopharmacology
    1. Laura B. Ferguson
    2. Angela R. Ozburn
    3. Igor Ponomarev
    4. Pamela Metten
    5. Matthew Reilly
    6. John C. Crabbe
    7. R. Adron Harris
    8. R. Dayne Mayfield

  • Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice

    Alcoholism: Clinical and Experimental Research
    1. Kush Purohit
    2. Puja K. Parekh
    3. Joseph Kern
    4. Ryan W. Logan
    5. Zheng Liu
    6. Yanhua Huang
    7. Colleen A. McClung
    8. John C. Crabbe
    9. Angela R. Ozburn

  • High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking

    Pharmacology Biochemistry and Behavior
    1. John C. Crabbe
    2. Angela R. Ozburn
    3. Pamela Metten
    4. Amanda Barkley-Levenson
    5. Jason P. Schlumbohm
    6. Stephanie E. Spence
    7. Wyatt R. Hack
    8. Lawrence C. Huang

  • NPAS2 regulation of anxiety-like behavior and GABAA receptors

    Frontiers in Molecular Neuroscience
    1. Angela R. Ozburn
    2. Joseph Kern
    3. Puja K. Parekh
    4. Ryan W. Logan
    5. Zheng Liu
    6. Edgardo Falcon
    7. Darius Becker-Krail
    8. Kush Purohit
    9. Nicole M. Edgar
    10. Yanhua Huang
    11. Colleen A. McClung

  • Functional implications of the CLOCK3111T/C single-nucleotide polymorphism

    Frontiers in Psychiatry
    1. Angela R. Ozburn
    2. Kush Purohit
    3. Puja K. Parekh
    4. Gabrielle N. Kaplan
    5. Edgardo Falcon
    6. Shibani Mukherjee
    7. Hannah M. Cates
    8. Colleen A. McClung