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Karen L. Gamble, Ph.D.

KAREN L. GAMBLE, Ph.D. Associate Professor
Department of Psychiatry & Behavioral Neurobiology
University of Alabama at Birmingham Medical Center
SC 715, 1720 7th Ave, S, Birmingham, AL 35294
Phone: (205) 934-4663
Fax: (205) 975-4879
E-mail: klgamble@uab.edu
Full CV
Website

Research Interest

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 of metabolism in animal models to humans, specifically by determining the impact of circadian misalignment on metabolic function under a shift work environment.

Publications

  1. Gamble, K.L., Novak, C.M., Paul, K.N., and Albers, H.E. (2003) Tetrodotoxin blocks the circadian effects of NMDA during the day but not at night. Neuroreport 14(4), 641-644.
  2. Gamble, K.L., Novak, C.M., and Albers, H.E. (2004). Neuropeptide y and n-methyl-d-aspartic acid interact within the suprachiasmatic nuclei to alter circadian phase. Neuroscience, 126, 559-565.
  3. Paul, K.N., Gamble, K.L., Fukuhara, C., Novak, C.M., Tosini, G., and Albers, H.E. (2004). Tetrodotoxin administration in the suprachiasmatic nucleus prevents NMDA-induced reductions in pineal melatonin without influencing Per1 and Per2 mRNA levels. Eur.J.Neurosci., 19, 2808-2814.
  4. Gamble, K.L., Ehlen, J.C., and Albers, H.E. (2005). Circadian control during the day and night: Role of neuropeptide Y Y5 receptors in the suprachiasmatic nucleus. Brain Res Bull., 65(6), 513-519.
  5. Gamble, K.L., Paul, K.N., Karom, M.C., Tosini, G., and Albers, H.E. (2006). Paradoxical effects of NPY in the suprachiasmatic nucleus. Eur J Neurosci 23(9), 2488-94.
  6. Ehlen, J.C., Novak, C.M., Gamble, K.L., Paul, K.N., and Albers, H.E. (2006). GABA-A receptor activation suppresses Period 1 mRNA and Period 2 mRNA in pattern similar to other nonphotic stimuli during the mid-subjective day. Eur J Neurosci, 23(12), 3328-36.
  7. Gamble, K.L., Allen, G., Zhou, T.R., and McMahon, D.G. (2007). Gastrin releasing peptide induces Per1 throughout the SCN and phase delays Per2-luc rhythms in a CREB-dependent manner. J Neurosci, 27(44), 12078-87.
  8. Ehlen, J. C., Novak, C. M., Karom, M. C., Gamble, K. L. & Albers, H. E. (2008). Interactions of GABAA Receptor Activation and Light on Period mRNA Expression in the Suprachiasmatic Nucleus. J Biol Rhythms 23, 16-25.
  9. Ciarleglio, C.M, Gamble, K.L., Axley, J.C., Strauss, B.R., Cohen, J., Colwell, C.S., and McMahon, D.G. (2009). Population Encoding by Circadian Clock Neurons Organizes Circadian Behavior. J Neurosci, 29(6), 1670-6.
  10. Gamble, K.L. and Ciarleglio, C.M. (2009). Ryanodine receptors are regulated by the circadian clock and implicated in gating photic entrainment. J Neurosci, 29(38), 11717-19.
  11. Xu, X., Graeff, R., Xie, O., Gamble, K.L., Mori, T., and Johnson, C.H. (2009). Comment on: "The Arabidopsis Circadian Clock Incorporates a cADPR-Based Feedback Loop." Science, 326 (5950), 230.
  12. Castanon-Cervantes, O.,  Wu, Mingwei, Ehlen,  J.C., Paul, K., Gamble, K.L., Johnson, R.L., Besing, R.C., Menaker, M., Gewirtz, A.T., and Davidson, A.J. (2010). “Disregulation of inflammatory responses by chronic circadian disruption.” J Immunol, 185(10), 5796-805.
  13. Ciarleglio, C.M., Axley, J.C., Strauss, B.R., Gamble, K.L. and McMahon, D.G. (2010). “Perinatal photoperiod imprints the circadian clock.” Nat Neurosci 14(1), 25-7.
  14. Durgan, D.J., Tsai, J., Grenett, M.H., Pat, B.M., Ratcliffe,W.F., Villegas-Montoya, C., Garvey, M.E., Nagendran, J., Dyck, J.R.B., Bray, M.S., Gamble, K.L., Gimble, J.M., and Young, M.E. (2010). “Evidence suggesting that the cardiomyocyte circadian clock modulates responsiveness of the heart to hypertrophic stimuli in mice.” Chronobiol Int, 185(10), 5796-5805.
  15. Gamble, K.L.*, Kudo, T., Colwell, C.S., and McMahon, D.G.* (2011). “Gastrin releasing peptide modulates fast delayed rectifier potassium current in Per1-expressing SCN neurons.” J Biol Rhythms, 26(2), 99-106. * Co-corresponding authors.
  16. Thompson, B.J., Jessen, T., Henry, L.K., Field, J.R., Gamble, K.L., Gresch, P.J., Carneiro, A.M., Horton, R.E., Chisnell, P.J., Belova, Y., McMahon, D.G., Daws, L.C., & Blakely, R.D. (2011). Transgenic elimination of high-affinity antidepressant and cocaine sensitivity in the presynaptic serotonin transporter. PNAS, 108(9), 3785-90.
  17. Gamble, K.L., Motsinger-Reif, A.A., Hida, A., Borsetti, H.M., Servick, S.V., Ciarleglio, C.M., Robbins, S., Hicks, J., Carver, K., Hamilton, N., Wells, N., Summar, M.L., McMahon, D.G., and Johnson, C.H. (2011). Shiftwork in nurses: Contribution of phenotypes and genotypes to adaptation. PLoS ONE, 6(4), e18395.
  18. Durgan, D.J., Pat, B.M., Laczy, B., Bradley, J.A., Tsai, J., Grenett, M.H., Ratcliffe,W.F., Brewer, R.A., Nagendran, J., Villegas-Montoya, C., Zou, C., Johnson, R.L., Dyck, J.R.B., Bray, M.S., Gamble, K.L., Chatham, J.C., and Young, M.E. (2011). O-GlcNAcylation: A novel post-translational modification linking myocardial metabolism and the cardiomyocyte circadian clock. J Biol Chem, 286(52) 44606-19.
  19. Fargason, R.E., Gamble, K.L., Avis, K.T., Besing, R.C., Jackson, C., Cates, M., and May, R.S. (2011). Ramelteon for Insomnia Related to Attention-Deficit/Hyperactivity Disorder (ADHD). Psychopharm Bull, 44(2), 1-22.
  20. Besing, R.C., Hablitz, L.M., Paul, J.R., Johnson, R.L., Prosser, R.A., and Gamble, K.L. (2012). NPY-induced phase shifts of PER2::LUC rhythms are mediated by long-term suppression of neuronal excitability in a phase-specific manner. Chronobiol Int, 29(2), 91-102. PMCID: PMC3568491
  21. Dougherty S.E., Reeves J.L., Lucas E.K., Gamble K.L., Lesort M., and Cowell R.M. (2012). Disruption of Purkinje cell function prior to huntingtin accumulation and cell loss in an animal model of Huntington Disease. Exp Neurol, 236(1), 171-8.
  22. Ruan, G., Gamble, K.L., Risner, M., Young, L., and McMahon, D.G. (2012). Divergent Roles of clock genes in retinal and suprachiasmatic nucleus circadian oscillators. PLoS ONE, 7(6), e38985.
  23. Jackson, C.R., Ruan, G., Aseem, F., Abey, J., Gamble, K., Stanwood, G., Palmiter, R.D., Iuvone, P.M., and McMahon, D.G. (2012). Retinal dopamine mediates multiple dimensions of light-adapted vision. J Neurosci, 32(27), 9359-68.
  24. DeAndrade, M.P., Johnson Jr., R.L., Unger, E.L., Zhang, L., van Groen, T., Gamble, K.L., and Li,Y. (2012). Motor restlessness, sleep disturbances, thermal sensory alterations, and elevated serum iron levels in Btbd9 mutant mice. Hum Mol Gen, 21(18), 3984-92.
  25. Bray, M.S., Ratcliffe, W.F., Grenett, M.H., Brewer, R.A., Gamble, K.L., and Young, M.E. (2012). Quantitative Analysis of Light-Phase Restricted Feeding Reveals Metabolic Dyssynchrony in Mice. Int J Obesity, 37(6):843-52.
  26. Zhou, W., Chen, L., Paul, J.R., Yang, S., Li F., Sampson, K., Woodgett, J.R., Beaulieu, J.M., Gamble, K.L., and Li, X. (2012). The Effects of Glycogen Synthase Kinase-3beta in Serotonin Neurons. PloS ONE, 7(8), e43262.
  27. Paul, J.R., Johnson, R.L., Jope, R.S., and Gamble, K.L. (2012). Disruption of circadian rhythmicity and suprachiasmatic action potential frequency in a mouse model with constitutive activation of glycogen synthase kinase-3. Neuroscience, 226, 1-9.
  28. Gamble, K.L., May, R.S., Besing, R.C., Tankersly, A.P., and Fargason, R.E. (2013). Delayed Sleep Timing and Symptoms in Adults with Attention-Deficit/Hyperactivity Disorder: A Controlled Actigraphy Study. Chronobiol Int, 30(4):598-606.
  29. Gamble, K.L. and Young, M.E. (2013). Metabolism as an Integral Cog in the Mammalian Circadian Clockwork. Crit Rev Biochem Mol Biol, 48(4):317-31.
  30. Filiano, A.N., Millender-Swain, T., Johnson Jr, R.L., Young, M.E., Gamble, K.L., and Bailey, S.M. (2013). Chronic Ethanol Consumption Disrupts the Core Molecular Clock and Diurnal Rhythms of Metabolic Genes in the Liver without affecting the SCN. PloS ONE, 8(8): e71684.
  31. Fargason R.E., White B.A., and Gamble, K.L. (2013). Complete sleep-wake cycle reversal related to ADHD detected by actigraphy. Annals of Clin Psych, 25(3):E8-E9.
  32. Fargason R.E., White S., Hollar A., and Gamble, K.L. (2012). Adults with Attention-deficit Hyperactivity Disorder without Insomnia have Subclinical Sleep Disturbances but not Circadian Delay: An ADHD Phenotype? J of Attention Dis, 17(7):583-8.
  33. Fargason R.E., Preston, T., Hammond, E., May, R., and Gamble, K.L. (2013). Treatment of attention deficit hyperactivity disorder insomnia with blue wavelength light-blocking glasses. Chronophys Ther, 3:1.
  34. Gamble, K.L., Resuehr, D., and Johnson, C.H. (2013). Shift work and circadian dysregulation of reproduction. Front Endocrinol, 4:92.
  35. Kudo, T., Tahara, Y., Gamble, K.L., McMahon, D.G., Block, G.D., and Colwell, C.S. (2013). Vasoactive intestinal peptide produces long-lasting changes in neural activity in the suprachiasmatic nucleus. J Neurophys, 110(5):1097-106.
  36. Avis, K.T., Gamble, K.L., Schwebel, D.C. (2013). Does Excessive Daytime Sleepiness Affect Children’s Pedestrian Safety? Sleep, 37(2): 283-287.
  37. Young, M.E., Brewer, R.A., Peliciari-Garcia, R.A., Collins, H.E., He, L., Birky, T.L., Peden, B.W., Thompson, E.G., Ammons, B., Bray, M.S., Chatham,  J.C., Wende, A.R., Yang, Q., Chow, C., Martino, T.A., Gamble, K.L. (2014). Cardiomyocyte-specific BMAL1 Plays Critical Roles in Metabolism, Signaling, and Maintenance of Contractile Function of the Heart. J Biol Rhythms, 29(4): 257-276.
  38. Gamble, K.L., Berry, R.D., Frank, S.J., and Young, M.E. (2014). Circadian Clock Control of Endocrine Factors. Nat Rev Endocrin, 10(8):466-75.
  39. Frank, E., Sidor, M.M., Gamble, K.L., Cirelli, C., Sharkey, K.M., Hoyle, N., Tikotzky, L., Talbot, L.S., McCarthy, M.J., and Hasler, B.P. (2013). Circadian clocks, brain function, and development. Ann NY Acad Sci, 1306: 43-67.
  40. Hablitz, L.M., Molzof, H.E., Paul, J.R, Johnson, R.L. and Gamble, K.L. (2014). Suprachiasmatic nucleus function and circadian entrainment are modulated by G protein-coupled inwardly-rectifying (GIRK) channels. J Physiol, 592(Pt 22):5079-92. PMCID: PMC4259544
  41. Volpicelli-Daley, L.A., Gamble, K.L., Schultheiss, C.E., Riddle, D.M., West, A.B., and Lee, V.M.-Y. (2014). Formation of α-Synuclein Lewy Neurite-like aggregates in Axons Impedes the Transport of Distinct Endosomes. Mol Biol Cell, 25(25):4010-23. PMCID: PMC4263445.
  42. Petrov, M.E. Clark,C.B., Molzof, H.E., Johnson, R.L., Cropsey, K.L., and Gamble, K.L. (2014). Sleep Strategies of Night Shift Nurses on Days Off: Which Ones are Best? Front Neurol, 5:277. PMCID: PMC4271573.
  43. Avis, K.T., Gamble, K.L., Schwebel, D.C. (2015). Obstructive Sleep Apnea Syndrome (OSAS) Increases Children’s Pedestrian Injury Risk. J Pediatrics, 166(1):109-14. PMCID: PMC4274212.
  44. Chou, C.F., Zhu, X., Gamble, K.L., Garvey, W.T., and Chen, C.Y. (2015). KSRP is critical in governing hepatic lipid metabolism through controlling Per2 expression. J Lipid Res, 56(2):227-40.
  45. Besing, R.C., Paul J.R., Hablitz, L.M., Rogers, C.O., Johnson, R.L., Young, M.E. and Gamble, K.L. (2015). Molecular clock gene regulation by glycogen synthase kinase 3 (GSK3) in the suprachiasmatic nucleus. J Biol Rhythms 30(2):155-60. PMCID: PMC4586074
  46. Gamble, K.L. and Young, M.E. (2015). Shift Work: The Early Bird Catches the Morning Shift. Curr Biol 25, R269–R293.
  47. Udoh US, Swain TM, Filiano AN, Gamble KL, Young ME, and Bailey SM (2015). Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice. Am J Physiol Gastrointest Liver Physiol, 308(11):G964-74. PMCID: PMC4451320.
  48. Hablitz, L.M., Molzof, H., Abrahamsson, K.E., Cooper, J.M., Prosser, R.A. and Gamble, K.L. (2015). GIRK channels mediate the nonphotic effects of exogenous melatonin. J Neurosci, 35(45):14957-65. PMCID: PMC4642232.
  49. Udoh US, Valcin, JA, Gamble KL, and Bailey SM (2015). The Molecular Circadian Clock and Alcohol-Induced Liver Injury. Biomolecules, 5(4): 2504-37. PMCID: PMC4693245.
  50. McMeekin LJ, Lucas EK, Meador-Woodruff JH, McCullumsmith RE, Hendrickson RC, Gamble KL, and Cowell RM. (2015). Deficiency in PGC-1α-Dependent Transcripts in the Cortex of Patients with Schizophrenia.  Schizophr Bull, 42(4):1009-17. PMCID: PMC4903048.
  51. Davis, J.A., Gamble, K.L. (2015).  Synchronized Time Keeping is Key to Healthy Mood Regulation (Commentary on Landgraf et al.). Eur J Neurosci, 43(10):1307-8. PMCID: PMC4874851.
  52. Peliciari-Garcia, R.A., Goel, M., Aristorenas, J.A., Shah, K., He, L. Yang, Q., Shalev, A., Bailey, S.M., Prabhu, S.D., Gamble, K.L., Chatham, J.C., and Young, M.E. (2016). Myocardial metabolic adaptation to increased fatty acid availability in vivo is dependent on the cardiomyocyte circadian clock in Mice. Mol and Cell Biol of Lipids, 1860(10):1579-95. PMCID: PMC4917492.
  53. Paul, J.R., DeWoskin, D.A., McMeekin, L.J., Cowell, R.M., Forger, D.B., and Gamble, K.L. (2016). Glycogen kinase synthase 3 links the molecular clock and excitability through activation of persistent sodium current. Nature Comm, 7: 13470.
  54. Molzof, H.E., Wirth, M.D., Birch, J.B., Shivappa, N., Hebert, J.R., Johnson, R.L., and Gamble, K.L. (2017). The impact of meal timing on cardiometabolic syndrome indicators in shift workers. Chronobiol Int, 34(3):337-348.
  55. Albers, H.W., Walton, J.C., Gamble, K.L., McNeill, J.K., and Hummer, D.L. (2017). The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus. Front Neuroendocrinol, 44:35-82.
  56. Paul, J.R., McKeown, A.S., Totsch, S.K., Mintz, E.M., Kraft, T.W., Cowell, R.M., and Gamble, K.L. (2017). Glycogen synthase kinase 3 regulates photic signaling in the suprachiasmatic nucleus. Eur J Neurosci, 45(8):1102-1110. PMCID: PMC5395359.
  57. Fargason, R.E., Fobian, A.D., Hablitz, L.M., Paul, J.R., White B.A., Cropsey, K.L., and Gamble, K.L. (2017). Correcting delayed circadian phase with bright light therapy predicts improvement in ADHD symptoms: A pilot study. J Psych Res, 91:105-110.
  58. Besing, R.C., Rogers, C.O., Paul J.R., Hablitz, L.M., Johnson, R.L., McMahon, L.L. and Gamble, K.L. (2017). Glycogen kinase synthase 3 regulates the hippocampal molecular clock and day-night differences in plasticity. Hippocampus, 27(8):890-898. PMCID: PMC5511075
  59. Udoh US, Valcin JA, Swain TM, Filiano AN, Gamble KL, Young ME, Bailey SM (2018). Genetic deletion of the circadian clock transcription factor BMAL1 and chronic alcohol consumption differentially alter hepatic glycogen in mice. Am J Physiol Gastrointest Liver Physiol, 314(3):G431-G447.
  60. Speed JS, Hyndman KA, Roth KJ, Heimlich JB, Kasztan M, Fox BM, Johnston JG, Becker BK, Jin C, Gamble KL, Young ME, Pollock JS, Pollock DM. (2018). High dietary sodium causes dyssynchrony of the renal molecular clock in rats. Am J Physiol Renal Physiol, 314(1):F89-F98.
  61. Paul JR, Munir HA, van Groen T, and Gamble K.L. (2018). Behavioral and SCN neurophysiological disruption in the Tg-SwDI mouse model of Alzheimer's disease. Neurobiol Dis, 114:194-200/
  62. Avis, K.T., Gamble, K.L., Schwebel, D.C. (2018). Effect of Positive Airway Pressure Therapy in Children with OSAS: Does PAP Use Reduce Pedestrian Injury Risk?. Sleep Health, 5(2):161-165.
  63. Molzof, H.E., Prapanjaroensin, A., Patel, V.H., Mokashi, M.V., and Gamble, K.L.* and Patricia, P.A.* (2018). Misaligned core body temperature rhythms impact cognitive performance of hospital shift work nurses. Neurobiology of Learning and Memory, 160:151-159. *Co-Corresponding Authors
  64. Resuehr, D., Johnson, R.L., Wu, G., Young, M.E., Hogenesch, J.B., and Gamble, K.L. (2019). Shift work disrupts circadian regulation of the human transcriptome in hospital nurses. J Biol Rhythms, 34(2):167-177.