William Joiner

Title(s)Associate Professor, Pharmacology
SchoolHealth Sciences
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    Collapse Biography 
    Collapse Education and Training
    Kenyon CollegeB.A.Biology
    Yale UniversityPh.D.Physiology
    University of PennsylvaniaPostdocNeuroscience

    Collapse Overview 
    Collapse Overview
    There are two major directions to my lab’s research:
    (1) We study the mechanisms that control the sleep/wake cycle in the model organism Drosophila melanogaster. Our studies have identified molecules that were previously unknown to regulate sleep, including endogenous prototoxins called Ly6 proteins that control excitability and synaptic transmission, as well as the RNA editing enzyme, ADAR, which controls short-term plasticity within a sleep-promoting neural circuit. Our studies are thus defining the biological basis of sleep regulation, the mechanistic link between sleep and synaptic plasticity, and ultimately novel potential targets for intervening in sleep-related disorders.
    (2) We also study the functions of Ly6 proteins in the mammalian brain. Our data indicate that various Ly6 proteins regulate the gating, trafficking and pharmacology of nicotinic acetylcholine receptors in different ways with important implications for nicotine addiction, schizophrenia and Alzheimer’s disease.

    Collapse Research 
    Collapse Research Activities and Funding
    Mechanisms underlying sleep homeostasis
    NIH/NIGMS R01GM125080Jul 1, 2017 - May 31, 2021
    Role: Principal Investigator
    Mechanisms Underlying Sleep Homeostasis
    NIH R01GM125080Jul 1, 2017 - May 31, 2021
    Role: Principal Investigator
    Molecular and anatomical basis of sleep regulation by SLEEPLESS
    NIH/NINDS R01NS072431Mar 15, 2011 - Feb 29, 2016
    Role: Principal Investigator

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Joiner WJ. The Neurobiological Basis of Sleep and Sleep Disorders. Physiology (Bethesda). 2018 09 01; 33(5):317-327. PMID: 30109824.
      View in: PubMed
    2. Joiner WJ. Unraveling the Evolutionary Determinants of Sleep. Curr Biol. 2016 10 24; 26(20):R1073-R1087. PMID: 27780049.
      View in: PubMed
    3. Barekat A, Gonzalez A, Mauntz RE, Kotzebue RW, Molina B, El-Mecharrafie N, Conner CJ, Garza S, Melkani GC, Joiner WJ, Lipinski MM, Finley KD, Ratliff EP. Using Drosophila as an integrated model to study mild repetitive traumatic brain injury. Sci Rep. 2016 05 04; 6:25252. PMID: 27143646; PMCID: PMC4855207.
    4. Landgraf D, Joiner WJ, McCarthy MJ, Kiessling S, Barandas R, Young JW, Cermakian N, Welsh DK. The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms. Neuropharmacology. 2016 08; 107:262-270. PMID: 27033596.
      View in: PubMed
    5. Wu M, Liu CZ, Joiner WJ. Structural Analysis and Deletion Mutagenesis Define Regions of QUIVER/SLEEPLESS that Are Responsible for Interactions with Shaker-Type Potassium Channels and Nicotinic Acetylcholine Receptors. PLoS One. 2016; 11(2):e0148215. PMID: 26828958.
      View in: PubMed
    6. Robinson JE, Paluch J, Dickman DK, Joiner WJ. ADAR-mediated RNA editing suppresses sleep by acting as a brake on glutamatergic synaptic plasticity. Nat Commun. 2016 Jan 27; 7:10512. PMID: 26813350; PMCID: PMC4737855.
    7. Seidner G, Robinson JE, Wu M, Worden K, Masek P, Roberts SW, Keene AC, Joiner WJ. Identification of Neurons with a Privileged Role in Sleep Homeostasis in Drosophila melanogaster. Curr Biol. 2015 Nov 16; 25(22):2928-38. PMID: 26526372; PMCID: PMC4654679 [Available on 11/16/16].
    8. Wu M, Puddifoot CA, Taylor P, Joiner WJ. Mechanisms of inhibition and potentiation of a4ß2 nicotinic acetylcholine receptors by members of the Ly6 protein family. J Biol Chem. 2015 Oct 02; 290(40):24509-18. PMID: 26276394; PMCID: PMC4591831 [Available on 10/02/16].
    9. Ratliff EP, Mauntz RE, Kotzebue RW, Gonzalez A, Achal M, Barekat A, Finley KA, Sparhawk JM, Robinson JE, Herr DR, Harris GL, Joiner WJ, Finley KD. Aging and Autophagic Function Influences the Progressive Decline of Adult Drosophila Behaviors. PLoS One. 2015; 10(7):e0132768. PMID: 26182057; PMCID: PMC4504520.
    10. Zhang S, Ross KD, Seidner GA, Gorman MR, Poon TH, Wang X, Keithley EM, Lee PN, Martindale MQ, Joiner WJ, Hamilton BA. Nmf9 Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies. PLoS Genet. 2015 Jul; 11(7):e1005344. PMID: 26131556.
      View in: PubMed
    11. Keene AC, Joiner WJ. Neurodegeneration: paying it off with sleep. Curr Biol. 2015 Mar 16; 25(6):R234-R236. PMID: 25784043.
      View in: PubMed
    12. Puddifoot CA, Wu M, Sung RJ, Joiner WJ. Ly6h regulates trafficking of alpha7 nicotinic acetylcholine receptors and nicotine-induced potentiation of glutamatergic signaling. J Neurosci. 2015 Feb 25; 35(8):3420-30. PMID: 25716842; PMCID: PMC4339353.
    13. Wu M, Robinson JE, Joiner WJ. SLEEPLESS is a bifunctional regulator of excitability and cholinergic synaptic transmission. Curr Biol. 2014 Mar 17; 24(6):621-9. PMID: 24613312; PMCID: PMC4059605.
    14. Heinrichsen ET, Zhang H, Robinson JE, Ngo J, Diop S, Bodmer R, Joiner WJ, Metallo CM, Haddad GG. Metabolic and transcriptional response to a high-fat diet in Drosophila melanogaster. Mol Metab. 2014 Feb; 3(1):42-54. PMID: 24567903; PMCID: PMC3929909.
    15. Joiner WJ, Friedman EB, Hung HT, Koh K, Sowcik M, Sehgal A, Kelz MB. Genetic and anatomical basis of the barrier separating wakefulness and anesthetic-induced unresponsiveness. PLoS Genet. 2013; 9(9):e1003605. PMID: 24039590; PMCID: PMC3764144.
    16. Dean T, Xu R, Joiner W, Sehgal A, Hoshi T. Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K(+) channels. J Neurosci. 2011 Aug 03; 31(31):11387-95. PMID: 21813698; PMCID: PMC3183472.
    17. Friedman EB, Sun Y, Moore JT, Hung HT, Meng QC, Perera P, Joiner WJ, Thomas SA, Eckenhoff RG, Sehgal A, Kelz MB. A conserved behavioral state barrier impedes transitions between anesthetic-induced unconsciousness and wakefulness: evidence for neural inertia. PLoS One. 2010 Jul 30; 5(7):e11903. PMID: 20689589; PMCID: PMC2912772.
    18. Wu MN, Joiner WJ, Dean T, Yue Z, Smith CJ, Chen D, Hoshi T, Sehgal A, Koh K. SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker. Nat Neurosci. 2010 Jan; 13(1):69-75. PMID: 20010822; PMCID: PMC2842941.
    19. Koh K, Joiner WJ, Wu MN, Yue Z, Smith CJ, Sehgal A. Identification of SLEEPLESS, a sleep-promoting factor. Science. 2008 Jul 18; 321(5887):372-6. PMID: 18635795; PMCID: PMC2771549.
    20. Wu MN, Koh K, Yue Z, Joiner WJ, Sehgal A. A genetic screen for sleep and circadian mutants reveals mechanisms underlying regulation of sleep in Drosophila. Sleep. 2008 Apr; 31(4):465-72. PMID: 18457233; PMCID: PMC2279757.
    21. Sehgal A, Joiner W, Crocker A, Koh K, Sathyanarayanan S, Fang Y, Wu M, Williams JA, Zheng X. Molecular analysis of sleep: wake cycles in Drosophila. Cold Spring Harb Symp Quant Biol. 2007; 72:557-64. PMID: 18419315.
      View in: PubMed
    22. Joiner WJ, Crocker A, White BH, Sehgal A. Sleep in Drosophila is regulated by adult mushroom bodies. Nature. 2006 Jun 08; 441(7094):757-60. PMID: 16760980.
      View in: PubMed
    23. Yuan Q, Joiner WJ, Sehgal A. A sleep-promoting role for the Drosophila serotonin receptor 1A. Curr Biol. 2006 Jun 06; 16(11):1051-62. PMID: 16753559.
      View in: PubMed
    24. Zhang Y, Joiner WJ, Bhattacharjee A, Rassendren F, Magoski NS, Kaczmarek LK. The appearance of a protein kinase A-regulated splice isoform of slo is associated with the maturation of neurons that control reproductive behavior. J Biol Chem. 2004 Dec 10; 279(50):52324-30. PMID: 15375169.
      View in: PubMed
    25. Bhattacharjee A, Joiner WJ, Wu M, Yang Y, Sigworth FJ, Kaczmarek LK. Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP. J Neurosci. 2003 Dec 17; 23(37):11681-91. PMID: 14684870.
      View in: PubMed
    26. Hoffman JF, Joiner W, Nehrke K, Potapova O, Foye K, Wickrema A. The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells. Proc Natl Acad Sci U S A. 2003 Jun 10; 100(12):7366-71. PMID: 12773623; PMCID: PMC165881.
    27. Joiner WJ, Basavappa S, Vidyasagar S, Nehrke K, Krishnan S, Binder HJ, Boulpaep EL, Rajendran VM. Active K+ secretion through multiple KCa-type channels and regulation by IKCa channels in rat proximal colon. Am J Physiol Gastrointest Liver Physiol. 2003 Jul; 285(1):G185-96. PMID: 12606302.
      View in: PubMed
    28. White BH, Osterwalder TP, Yoon KS, Joiner WJ, Whim MD, Kaczmarek LK, Keshishian H. Targeted attenuation of electrical activity in Drosophila using a genetically modified K(+) channel. Neuron. 2001 Sep 13; 31(5):699-711. PMID: 11567611.
      View in: PubMed
    29. Joiner WJ, Khanna R, Schlichter LC, Kaczmarek LK. Calmodulin regulates assembly and trafficking of SK4/IK1 Ca2+-activated K+ channels. J Biol Chem. 2001 Oct 12; 276(41):37980-5. PMID: 11495911.
      View in: PubMed
    30. Khanna R, Chang MC, Joiner WJ, Kaczmarek LK, Schlichter LC. hSK4/hIK1, a calmodulin-binding KCa channel in human T lymphocytes. Roles in proliferation and volume regulation. J Biol Chem. 1999 May 21; 274(21):14838-49. PMID: 10329683.
      View in: PubMed
    31. Joiner WJ, Tang MD, Wang LY, Dworetzky SI, Boissard CG, Gan L, Gribkoff VK, Kaczmarek LK. Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nat Neurosci. 1998 Oct; 1(6):462-9. PMID: 10196543.
      View in: PubMed
    32. Joiner WJ, Wang LY, Tang MD, Kaczmarek LK. hSK4, a member of a novel subfamily of calcium-activated potassium channels. Proc Natl Acad Sci U S A. 1997 Sep 30; 94(20):11013-8. PMID: 9380751; PMCID: PMC23566.
    33. Ketchum KA, Joiner WJ, Sellers AJ, Kaczmarek LK, Goldstein SA. A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature. 1995 Aug 24; 376(6542):690-5. PMID: 7651518.
      View in: PubMed
    34. McCormack K, Joiner WJ, Heinemann SH. A characterization of the activating structural rearrangements in voltage-dependent Shaker K+ channels. Neuron. 1994 Feb; 12(2):301-15. PMID: 8110460.
      View in: PubMed