Indiana University
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The Gill Center for Biomolecular Science

Ken Mackie | Faculty

Ken MackieProfessor, Department of Psychological and Brain Sciences and Program in Neuroscience

Office: MSBII 120
TEL: 812-855-2042
Email: kmackie@indiana.edu

Lab Website

Education

  • Brown University, ScB, Engineering, 1980
  • Yale University, MD, 1984

Research Interests

  • Regulation of CB1 cannabinoid receptor signaling
  • Regulation of endocannabinoid production
  • Role of endocannabinoids in synaptic plasticity
  • Novel cannabinoid receptors

His research program focuses on cannabinoid receptors, the cell surface receptors responsible for most of the psychoactive and therapeutic actions of cannabis. His group uses a variety of techniques, including electrophysiological, molecular, immunological, and imaging, to better understand how cannabinoid receptors signal and how their signaling interacts with other cellular processes. Much of the current work in his lab centers on endogenous cannabinoids (endocannabinoids), compounds produced by the body that interact with cannabinoid receptors. These molecules have been implicated in processes as diverse as memory, analgesia, anxiety, schizophrenia, and obesity. One of the recent results from his group suggests that cannabis produces some of its effects by blocking the normal actions of endocannabinoids. This contrasts with the mode of action of opiates, which appear to produce their psychoactivity by mimicking the effects of endogenous opiates (endorphins).

Representative Publications

  • Berghuis, P., A.M. Rajnicek, Y.M. Morozov, R.A. Ross, J. Mulder, K. Monory, G. Marsicano, B. Lutz, M. Matteoli, A. Canty, Y. Yanagawa, P. Rakic, K. Mackie & T. Harkany.  2007.  Hardwiring the brain:  Endocannabinoids control axon guidance.  Science. 316:1212-1216.
  • Daigle T.L., C. S. Kearn, & K. Mackie. 2008. Rapid CB1 cannabinoid receptor desensitization defines the time course of ERK1/2 MAP kinase signaling. Neuropharmacol. 54:36-44.
  • Daigle, T.L, M.L. Kwok, & K. Mackie.2008.  Regulation of CB1 receptor internalization by a promiscuous phosphorylation-dependent mechanism.  J. Neurochem. 106:70-82.
  • Lauckner, J.E., J.B. Jensen, H.-Y. Chen, H.-C. Lu, B. Hille, & K. Mackie.  2008.  GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current.  Proc. Natl. Acad. Sci. USA. 105:2699-2704.
  • Kellogg, R., K. Mackie & A. Straiker.  2009. Cannabinoid CB1 receptor-dependent long-term depression in autaptic excitatory neurons.  J. Neurophysiol.  102:1160-1171.
  • Straiker, A., S.S. Hu, J. Long, A. Arnold, J. Wager-Miller, B. Cravatt & K. Mackie. 2009.  Monoacyl glycerol lipase (MGL) limits the duration of endocannabinoid-mediated depolarization-induced suppression of excitation (DSE) in autaptic hippocampal neurons.  Mol. Pharmacol. 76:1220-7.
  • Atwood, B.K., J. Huffman, A. Straiker, & K. Mackie. 2010.  JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious CB1 receptor agonist.  Br. J. Pharmacol. 160:585-93.
  • Catterall, W.A. and K. Mackie.  2010. Local Anesthetics.  in Goodman and Gilman's:  The Pharmacological Basis of Therapeutics.  (Ed. J.G. Hardman, L.E. Limbard, P.B. Molinoff, T.W. Rall, and R.W. Ruddon) McGraw Hill.
  • Wu, C.-S., J. Zhu, J. Wager-Miller, S. Wang, D. O’Leary, K. Monory, B. Lutz, K. Mackie, & H.-C. Lu.  2010.  Requirement of cannabinoid CB1 receptor in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections.  Eu. J. Neurosci. 32:693-706.
  • Atwood, B.K. & K. Mackie.  2010.  CB2 in neurons:  A receptor with an identity crisis.  Br. J. Pharmacol. 160:467-79
  • Keimpema, E., K. Barbaras, Y.M. Morozov, G. Tortoriello, M. Torii, G. Cameron, M.R. Elphick, M. Egertova, Y. Yanagawa, M. Watanabe, K. Mackie & T. Harkany.  2010.  Differential subcellular recruitment of monoacylglycerol lipase generates spatial specificity of 2-arachidonoyl glycerol signaling during axonal pathfinding.  J. Neurosci.  30:13992-4007.
  • Atwood, B.K., D. Lee, A. Straiker, T.S. Widlanski, & K. Mackie.  2011.  CP47,497-C8 and JWH073, commonly found in ‘spice’ herbal blends, are potent and efficacious CB1 cannabinoid receptor agonists.  Eur. J. Pharmacol. 659:139-45.
  • Straiker, A., J. Wager-Miller, & K. Mackie.  In press.  Differential signaling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurons. Br. J. Pharmacol.