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Faculty Detail    
Name KAREN LYNNETTE GAMBLE
 
Campus Address SC 720 Zip 0017
Phone 205-934-4663
E-mail klgamble@uab.edu
Other websites
     

Certifications
Clinical and Translational Science Training Program, UAB CCTS  2012 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Psychiatry   Psych - Behavioral Neurobiology Assistant Professor
Secondary  Neurobiology  Neurobiology Assistant Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Assistant Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Assistant Professor
Center  Nutrition Sciences   Nutrition Obesity Res Ctr (NORC) Assistant Professor
Center  Vision Sciences  Vision Science Research Center Assistant Professor

Biographical Sketch 
King College
Bristol, TN
B.A.(Psychology)
1993-1996

Georgia State University
Atlanta, GA
M.A. (Neuropsychology)
1999-2001

Georgia State University
Atlanta, GA
Ph.D. (Neuropsychology)
2001-2004

Vanderbilt University, Nashville, TN
Postdoctoral Fellowship
Biological Sciences
2004-2009

Society Memberships
Organization Name Position Held Org Link
Society for Neuroscience  Member  www.sfn.org 
Society for Research in Biological Rhythms  Member  www.srbr.org 
Society for Research in Biological Rhythms  2012 Facilities Coordinator   
Society for Research in Biological Rhythms  2012 Travel Awards Committee, Member   
Society for Research in Biological Rhythms  2014 Trainee Day Committee, Organizer   
Society for Research in Biological Rhythms  2012 Trainee Day Committee, Member   

Research/Clinical Interest
Title
Description
Mechanisms and Entrainment of Circadian Clocks The mammalian brain’s primary biological clock (the suprachiasmatic nucleus or SCN) drives daily physiological and behavioral rhythms that persist in the absence of environmental time cues with a near-24 hour period. When the endogenous clock is misaligned with the external environment such as during jet lag and shift work, serious repercussions can result, not only for the circadian system but also for the entire body. For example, shift work is associated with an increased risk of gastrointestinal disorders, cardiovascular disease, depression, and cancer. Clinically, sleep and circadian rhythm disturbances have been linked to neurodegenerative diseases as well as mood and developmental disorders. Given the range of circadian physiological processes, it is not surprising that ~24-hour rhythms in the expression of the core clock genes or electrical activity have been discovered throughout the brain and body. Therefore, determining underlying mechanisms for the types of stimuli that can “reset” and re-align the clock with the environment is important for developing novel therapeutic approaches. The overall goal of my research program is to investigate how the mammalian clock integrates environmental and molecular signals into robust behavioral and physiological rhythms. The complementary and translational side of this goal is to determine how neurological diseases and disruptive environments (such as shift work) result in dysregulated circadian rhythms that exacerbate disease symptoms. To this end, the projects in my lab can be divided into three primary categories: (i) underlying neurophysiological mechanisms of entrainment in of SCN neurons, (ii) the role of rhythmic regulation of glycogen synthase kinase 3 in the brain and periphery, and (iii) circadian misalignment in shift work nurses. Our laboratory is currently using circadian behavioral analysis, tissue-level imaging and pharmacology, as well as targeted fluorescence electrophysiology in transgenic mouse models to investigate the neural circuitry of the SCN. In clinical studies of shift work nurses, we are measuring circadian rhythms in sleep-wake behavior (actigraphy), diet/nutrition, plasma metabolites, and clock gene expression rhythms in peripheral mononuclear cells to determine the effects of shift work on circadian misalignment.

Selected Publications 
Publication PUBMEDID
Fargason R.E., White S., Hollar A., and Gamble, K. (2012). Adults with Attention-deficit Hyperactivity Disorder without Insomnia have Subclinical Sleep Disturbances but not Circadian Delay: An ADHD Phenotype? J of Attention Dis, in press.  22997357 
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.  22986169 
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.  22912839 
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, in press.  22907695 
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.  22764243 
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.  22701739 
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.  22678064 
Dougherty SE, Reeves JL, Lucas EK, Gamble KL, Lesort M, and Cowell RM (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.  22579526 
Besing, R.C., Hablitz, L.M., Paul, J.R., Johnson, R.L., Prosser, R.A., & 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.  22324550 
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. Journal of Biol Chem, 286(52) 44606-19.  22069332 
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.  21533241 
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.  21454290 
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.  21452915 
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.  21282638 
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.  21131951 
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.  20944004 
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.  19815758 
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.  19776257 
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.  19211874 
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.  18258754 
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  17978049 
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.  16820022 
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.  16706855 
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.  15862923 
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.  15183505 
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.  15147314 
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.  12657903 
Gamble, K.L., May, R.S., Besing, R.C., Tankersly, A.P., and Fargason, R.E. (2012). Delayed Sleep Timing and Symptoms in Adults with Attention-Deficit/Hyperactivity Disorder: A Controlled Actigraphy Study. Chronobiol Int, in press.   
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.
 
 

Keywords
circadian rhythms, biological clocks, shift work, entrainment, suprachiasmatic nucleus