• The overall goal of my research program is to investigate environmental modulation of circadian clock function in mammalian systems and the contribution of clock disruption to pathological disease. One of the most exciting discoveries that has emerged in recent years is that the circadian molecular clock regulates excitability in neurons that are spontaneously active in the absence of synaptic input. Although the intrinsic 24-h rhythm in membrane properties of neurons of the suprachiasmatic nucleus (SCN) has been known for over 30 years, it is surprising that we know very little about how the brain’s circadian clock regulates circadian rhythmicity throughout the body as well as in other brain regions. We are interested in how nutrition (high caloric diets, meal timing) and disease (obesity, neurodegeneration) influence clock-driven changes in physiology and behavior in brain regions such as the SCN, hippocampus and substantia nigra. A second, related interest of the laboratory is translation what we have learned about circadian regulation in animal models to humans, specifically by determining the impact of environmental circadian misalignment (e.g., shift work) or addiction (e.g., smoking) on circadian rhythmicity of behavior and physiology.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2023 Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop ReportHypertension.  80:503-522. 2023
    2023 Circadian regulation of dentate gyrus excitability mediated by G-protein signalingCell Reports.  42. 2023
    2023 Timed feeding aligns the adipocyte clock to optimize thermogenesis when eating a high-fat dietCell Metabolism.  35:7-9. 2023
    2022 Examination of Diurnal Variation and Sex Differences in Hippocampal Neurophysiology and Spatial MemoryeNeuro.  9. 2022
    2022 Circadian disruption of hippocampus in an early senescence male mouse model 2022
    2022 Nightshift Work and Nighttime Eating Are Associated With Higher Insulin and Leptin Levels in Hospital NursesFrontiers in Endocrinology.  13. 2022
    2022 Examination of diurnal variation and sex differences in hippocampal neurophysiology and spatial memory 2022
    2022 Short-term daytime restricted feeding in rats with high salt impairs diurnal variation of Na þ excretion 2022
    2021 Depleting hypothalamic somatostatinergic neurons recapitulates diabetic phenotypes in mouse brain, bone marrow, adipose and retinaDiabetologia.  64:2575-2588. 2021
    2021 Dysregulated clock gene expression and abnormal diurnal regulation of hippocampal inhibitory transmission and spatial memory in amyloid precursor protein transgenic miceNeurobiology of Disease.  158. 2021
    2021 Time-restricted feeding rescues high-fat-diet-induced hippocampal impairmentiScience.  24. 2021
    2021 Chronobiology of Natriuretic Peptides and Blood Pressure in Lean and Obese IndividualsJournal of the American College of Cardiology.  77:2291-2303. 2021
    2021 Workshop report. Circadian rhythm sleep-wake disorders: Gaps and opportunitiesSleep.  44. 2021
    2021 Glucagon receptor signaling regulates weight loss via central KLB receptor complexesJCI Insight.  6. 2021
    2021 Timing of Food Intake Drives the Circadian Rhythm of Blood PressureFunction.  2. 2021
    2020 High-Fat and High-Sucrose Diets Impair Time-of-Day Differences in Spatial Working Memory of Male MiceObesity.  28:2347-2356. 2020
    2020 Rhythms in Neurometabolism Decline with AgeNeuroscience.  448:299. 2020
    2020 Alcohol and Liver Clock Disruption Increase Small Droplet Macrosteatosis, Alter Lipid Metabolism and Clock Gene mRNA Rhythms, and Remodel the Triglyceride Lipidome in Mouse LiverFrontiers in Physiology.  11. 2020
    2020 Diurnal, metabolic and thermogenic alterations in a murine model of accelerated aging 2020
    2020 Circadian rhythmicity and the community of clockworkersEuropean Journal of Neuroscience.  51:2314-2328. 2020
    2020 Circadian regulation of membrane physiology in neural oscillators throughout the brainEuropean Journal of Neuroscience.  51:109-138. 2020
    2019 Effect of positive airway pressure therapy in children with obstructive sleep apnea syndrome: does positive airway pressure use reduce pedestrian injury risk?Sleep Health.  5:161-165. 2019
    2019 Misaligned core body temperature rhythms impact cognitive performance of hospital shift work nursesNeurobiology of Learning and Memory.  160:151-159. 2019
    2019 Shift Work Disrupts Circadian Regulation of the Transcriptome in Hospital NursesJournal of Biological Rhythms.  34:167-177. 2019
    2018 Editorial overview: Circadian rhythms 2018
    2018 Behavioral and SCN neurophysiological disruption in the Tg-SwDI mouse model of Alzheimer's diseaseNeurobiology of Disease.  114:194-200. 2018
    2018 Genetic deletion of the circadian clock transcription factor BMAL1 and chronic alcohol consumption differentially alter hepatic glycogen in mice 2018
    2018 Circadian Rhythms in Regulation of Brain Processes and Role in Psychiatric DisordersNeural Plasticity.  2018. 2018
    2018 High dietary sodium causes dyssynchrony of the renal molecular clock in rats 2018
    2017 Correcting delayed circadian phase with bright light therapy predicts improvement in ADHD symptoms: A pilot studyJournal of Psychiatric Research.  91:105-110. 2017
    2017 GSK3 activity regulates rhythms in hippocampal clock gene expression and synaptic plasticity 2017
    2017 Glycogen synthase kinase 3 regulates photic signaling in the suprachiasmatic nucleusEuropean Journal of Neuroscience.  45:1102-1110. 2017
    2017 The impact of meal timing on cardiometabolic syndrome indicators in shift workers 2017
    2017 The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleusFrontiers in Neuroendocrinology.  44:35-82. 2017
    2016 Regulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitabilityNature Communications.  7. 2016
    2016 Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice 2016
    2016 Cortical PGC-1?-dependent transcripts are reduced in postmortem tissue from patients with schizophreniaSchizophrenia Bulletin.  42:1009-1017. 2016
    2016 Sleep-deprived motor vehicle operators are unfit to drive: A multidisciplinary expert consensus statement on drowsy drivingSleep Health.  2:94-99. 2016
    2016 Synchronized time-keeping is key to healthy mood regulation (Commentary on Landgraf et al.)European Journal of Neuroscience.  43:1307-1308. 2016
    2015 GIRK channels mediate the nonphotic effects of exogenous melatonin 2015
    2015 The molecular circadian clock and alcohol-induced liver injuryBiomolecules.  5:2504-2537. 2015
    2015 Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice 2015
    2015 Circadian rhythmicity of active GSK3 isoforms modulates molecular clock gene rhythms in the suprachiasmatic nucleusJournal of Biological Rhythms.  30:155-160. 2015
    2015 KSRP is critical in governing hepatic lipid metabolism through controlling Per2 expressionJournal of Lipid Research.  56:227-240. 2015
    2015 Circadian biology: The early bird catches the morning shiftCurrent Biology.  25:R269-R271. 2015
    2015 Obstructive sleep apnea syndrome increases pedestrian injury risk in childrenJournal of Pediatrics.  166:109-114. 2015
    2014 Formation of α-synuclein lewy neurite-like aggregates in axons impedes the transport of distinct endosomesMolecular Biology of the Cell.  25:4010-4023. 2014
    2014 Cardiomyocyte-specific BMAL1 plays critical roles in metabolism, signaling, and maintenance of contractile function of the heartJournal of Biological Rhythms.  29:257-276. 2014
    2014 Does excessive daytime sleepiness affect children's pedestrian safety?Sleep.  37:283-287. 2014
    2014 Circadian clock control of endocrine factorsNature Reviews Endocrinology.  10:466-475. 2014
    2014 Sleep strategies of night-shift nurses on days off: Which ones are most adaptive?Frontiers in Neurology.  5. 2014
    2014 Suprachiasmatic nucleus function and circadian entrainment are modulated by G protein-coupled inwardly rectifying (GIRK) channels 2014
    2013 Adults With ADHD-Without Insomnia History Have Subclinical Sleep Disturbance but Not Circadian Delay: An ADHD Phenotype?Journal of Attention Disorders.  17:583-588. 2013
    2013 Shift work and circadian dysregulation of reproductionFrontiers in Endocrinology.  4. 2013
    2013 Vasoactive intestinal peptide produces long-lasting changes in neural activity in the suprachiasmatic nucleusJournal of Neurophysiology.  110:1097-1106. 2013
    2013 Chronic Ethanol Consumption Disrupts the Core Molecular Clock and Diurnal Rhythms of Metabolic Genes in the Liver without Affecting the Suprachiasmatic NucleusPLoS One.  8. 2013
    2013 Complete sleep-wake cycle reversal related to ADHD detected by actigraphyAnnals of Clinical Psychiatry.  25. 2013
    2013 Metabolism as an integral cog in the mammalian circadian clockworkCritical Reviews in Biochemistry and Molecular Biology.  48:317-331. 2013
    2013 Quantitative analysis of light-phase restricted feeding reveals metabolic dyssynchrony in miceInternational Journal of Obesity.  37:843-852. 2013
    2013 Delayed sleep timing and symptoms in adults with attention-deficit/ hyperactivity disorder: A controlled actigraphy study 2013
    2013 Circadian clocks, brain function, and developmentAnnals of the New York Academy of Sciences.  1306:43-67. 2013
    2013 Complete sleep-wake cycle reversal related to ADHD detected by actigraphyAnnals of Clinical Psychiatry.  25:307-308. 2013
    2012 Disruption of circadian rhythmicity and suprachiasmatic action potential frequency in a mouse model with constitutive activation of glycogen synthase kinase 3Neuroscience.  226:1-9. 2012
    2012 Motor restlessness, sleep disturbances, thermal sensory alterations and elevated serum iron levels in BTBD9 mutant miceHuman Molecular Genetics.  21:3984-3992. 2012
    2012 The effects of glycogen synthase kinase-3beta in serotonin neuronsPLoS One.  7. 2012
    2012 Retinal dopamine mediates multiple dimensions of light-adapted vision 2012
    2012 Disruption of Purkinje cell function prior to huntingtin accumulation and cell loss in an animal model of Huntington DiseaseExperimental Neurology.  236:171-178. 2012
    2012 Divergent roles of clock genes in retinal and suprachiasmatic nucleus circadian oscillatorsPLoS One.  7. 2012
    2012 Neuropeptide Y-induced phase shifts of PER2::LUC rhythms are mediated by long-term suppression of neuronal excitability in a phase-specific manner 2012
    2011 O-glcnacylation, novel post-translational modification linking myocardial metabolism and cardiomyocyte circadian clockJournal of Biological Chemistry.  286:44606-44619. 2011
    2011 Ramelteon for insomnia related to attention-deficit/ hyperactivity disorder (ADHD)Psychopharmacology bulletin.  44. 2011
    2011 Shift work in nurses: Contribution of phenotypes and genotypes to adaptationPLoS One.  6. 2011
    2011 Erratum: Transgenic elimination of high-affinity antidepressant and cocaine sensitivity in the presynaptic serotonin transporter (Proceedings of the National Academy of Sciences of the United States of America (2011) 108, 9, (3785-3790) DOI: 10.1073/pnas.1011920108) 2011
    2011 Evidence suggesting that the cardiomyocyte circadian clock modulates responsiveness of the heart to hypertrophic stimuli in mice 2011
    2011 Gastrin-releasing peptide modulates fast delayed rectifier potassium current in Per1-expressing SCN neuronsJournal of Biological Rhythms.  26:99-106. 2011
    2011 Transgenic elimination of high-affinity antidepressant and cocaine sensitivity in the presynaptic serotonin transporter 2011
    2011 Perinatal photoperiod imprints the circadian clockNature Neuroscience.  14:25-27. 2011
    2010 Dysregulation of inflammatory responses by chronic circadian disruptionJournal of Immunology.  185:5796-5805. 2010
    2009 Comment on "the Arabiclopsis circadian clock incorporates a cADPR-based feedback loop"Science.  326. 2009
    2009 Ryanodine receptors are regulated by the circadian clock and implicated in gating photic entrainment 2009
    2009 Beyond Prozac: Generation and characterization of SSRI Insensitive Transgenic Mice 2009
    2009 Population encoding by circadian clock neurons organizes circadian behavior 2009
    2008 Interactions of GABAA receptor activation and light on period mRNA expression in the suprachiasmatic nucleusJournal of Biological Rhythms.  23:16-25. 2008
    2007 Gastrin-releasing peptide mediates light-like resetting of the suprachiasmatic nucleus circadian pacemaker through cAMP response element-binding protein and Per1 activation 2007
    2006 GABAA receptor activation suppresses Period 1 mRNA and Period 2 mRNA in the suprachiasmatic nucleus during the mid-subjective dayEuropean Journal of Neuroscience.  23:3328-3336. 2006
    2006 Paradoxical effects of NPY in the suprachiasmatic nucleusEuropean Journal of Neuroscience.  23:2488-2494. 2006
    2005 Circadian control during the day and night: Role of neuropeptide Y Y5 receptors in the suprachiasmatic nucleusBrain Research Bulletin.  65:513-519. 2005
    2004 Neuropeptide Y and N-methyl-D-aspartic acid interact within the suprachiasmatic nuclei to alter circadian phaseNeuroscience.  126:559-565. 2004
    2004 Tetrodotoxin administration in the suprachiasmatic nucleus prevents NMDA-induced reductions in pineal melatonin without influencing Per1 and Per2 mRNA levelsEuropean Journal of Neuroscience.  19:2808-2814. 2004
    2004 Tetrodotoxin administration in the suprachiasmatic nucleus prevents NMDA-induced reductions in pineal melatonin without influencing Per1 and Per2 mRNA levelsEuropean Journal of Neuroscience.  19:2808-2814. 2004
    2003 Tetrodotoxin blocks the circadian effects of NMDA during the day but not at nightNeuroReport.  14:641-644. 2003

    Research Overview

  • Chronobiology, Sleep, Circadian Rhythms, Neuroscience, Electrophysiology, Neurodegenerative Diseases, Smoking, Shift Work
  • Investigator On

  • A Sleep and Media Intervention to Improve Adolescents Weight and Risk of Type 2 Diabetes  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS
  • Alcohol-Induced Mitochondrial Dysfunction and the Hepatocyte Clock  awarded by National Institute on Alcohol Abuse and Alcoholism/NIH/DHHS
  • Circadian Changes in Network Excitability and Alzheimer Disease Pathogenesis  awarded by National Institute on Aging/NIH/DHHS
  • Circadian Changes in Network Excitability and Alzheimer Disease Pathogenesis  awarded by National Institute on Aging/NIH/DHHS
  • Circadian Rhythms and Alcohol in the BMAL1 Knockout Rat  awarded by National Institute on Alcohol Abuse and Alcoholism/NIH/DHHS
  • Circadian and Sleep Mechanisms among Racial Groups for Nicotine Dependence, Craving, and Withdrawal  awarded by National Institute on Drug Abuse/NIH/DHHS
  • Consequences of Noradrenergic Degeneration in the Novel TgF344-AD Rat Model  awarded by National Institute on Aging/NIH/DHHS
  • Energetics, Disparities, & Lifespan: A Unified Hypothesis  awarded by National Institute on Aging/NIH/DHHS
  • Glucagon Mediated Potentiation of Insulin Sensitivity in Glucose Metabolism  awarded by National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS
  • Hepatocyte Clock and Alcoholic Fatty Liver Injury  awarded by National Institute on Alcohol Abuse and Alcoholism/NIH/DHHS
  • In Vivo Experience with NRT to Increase Adherence and Smoking Abstinence  awarded by National Institute on Drug Abuse/NIH/DHHS
  • Integrating Novel Mechanisms Controlling Sodium Excretion and Blood Pressure  awarded by National Heart, Lung, and Blood Institute/NIH/DHHS
  • Integrating Novel Mechanisms Controlling Sodium Excretion and Blood Pressure - AD Supplement: Salt-Dependent Hypertension and the Central Clock  awarded by National Heart, Lung, and Blood Institute/NIH/DHHS
  • Natriuretic Peptide-Renin-Angiotensin-Aldosterone System Rhythm Axis and Nocturnal Blood Pressure  awarded by National Heart, Lung, and Blood Institute/NIH/DHHS
  • Role of The Hippocampal-mPFC Pathway in Social Memory Deficits in Autism  awarded by National Institute of Mental Health/NIH/DHHS
  • Short Chain Dehydrogenases in Retinol/Sterol Metabolism  awarded by National Institute of Arthritis & Musculoskeletal & Skin Diseases/NIH/DHHS
  • Timing of Sodium Intake and Nocturnal Sodium Excretion and Blood Pressure in Obese African Americans  awarded by National Heart, Lung, and Blood Institute/NIH/DHHS
  • Transcriptional Regulation of Metabolism in Neurons  awarded by SOUTHERN RESEARCH INSTITUTE
  • Using Early Time-Restricted Feeding and Timed Light Therapy to Improve Glycemic Control in Adults with Type 2 Diabetes  awarded by DOD - Department of Defense
  • Teaching Overview

  • One of the most rewarding aspects of my job as a faculty member is training the next generation of scientists in my laboratory and in the classroom. Since starting my independent laboratory in 2009, I have mentored postdocs, graduate students, undergraduate students, and summer high school students. In addition, I have also been rewarded with the opportunity to mentor ~40 other graduate students by serving as the Neuroscience Theme Director of the Graduate Biomedical Sciences (GBS) program from 2016-2021. I have served on their thesis committees for many of these students. Throughout my career and training, I have realized the importance of obtaining extramural funding. As a predoctoral and postdoctoral fellow, I was granted individual F31 and F32 awards as well as a position on a postdoctoral T32 training grant. Finally, I completed my training with one of the first cycles of NIH K99/R00 awards. Together, these experiences have taught me the necessary building blocks for a successful training program. My graduate trainees have successfully received F31 applications. In the classroom, I have served as the course director for the Neuroscience Graduate Student Summer Seminar Series and currently direct the Introduction to Biostatistics and the Circadian Clocks Journal Club. In addition, I was invited to lead two workshops on for Trainee Day at the 2012 Society for Research in Biological Rhythms (SRBR) meeting. After this rewarding experience, I served as the Professional Development Day director for the 2014 and 2016 SRBR meetings. In 2014, I served as one of the invited instructors for the International Chronobiology Summer School, where I directed workshops on “Clock control of excitability” and “Statistical Analysis of Rhythmic Data.”
  • Education And Training

  • Vanderbilt University Biological Sciences, Postdoctoral Fellowship
  • Doctor of Philosophy in Neuroscience, Georgia State University 2004
  • Master of Social or Behavioral Sciences in Psychology, Georgia State University 2001
  • Bachelor of Arts in Psychology, King College 1996
  • Full Name

  • Karen Gamble