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Indiana University Bloomington

Ken Mackie

Dr. Ken Mackie

Professor

Interim Director of Gill Center

 

kmackie [at] indiana.edu

office: MSBII 120 | (812)855-2042

lab: MSBII 142 | (812)856-2684

 

Regulation of CB1 cannabinoid receptor signaling; regulation of endocannabinoid production; Role of endocannabinoids in synaptic plasticity; novel cannabinoid receptors

Educational Background

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

Areas of Study

  • Neuroscience

Research Topics

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

Research Summary:

The Mackie lab examines the role and function of the endocannabinoid system by using a combination of electrophysiological, imaging, biochemical and immunological approaches. The endocannabinoid system is comprised of cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes that regulate the production and degradation of endocannabinoids. ?9THC, the principal psychoactive component of cannabis, interacts with this system to produce the classic effects of cannabis intoxication. In addition, this system is widely involved in multiple physiologically important processes including memory, motivation, movement, analgesia, and emesis. Through our studies, we hope to better understand the implications of social and therapeutic use of drugs that influence this fascinating system.

Representative Publications

Keimpema, E., G. Tortoriello, A. Alpar, S. Capsoni, I. Arisi, D. Calvigioni, S. S. Hu, A. Cattaneo, P. Doherty, K. Mackie and T. Harkany. 2013. Nerve growth factor scales endocannabinoid signaling by regulating monoacylglycerol lipase turnover in developing cholinergic neurons. PNAS USA 110(5): 1935-40.

Shonesy, B. C., X. Wang, K. L. Rose, T. S. Ramikie, V. S. Cavener, T. Rentz, A. J. Baucum, 2nd, N. Jalan-Sakrikar, K. Mackie, D. G. Winder, S. Patel and R. J. Colbran. 2013. CaMKII regulates diacylglycerol lipase-alpha and striatal endocannabinoid signaling. Nature Neuroscience 16(4): 456-63.

Jung, K. M., M. Sepers, C. M. Henstridge, O. Lassalle, D. Neuhofer, H. Martin, M. Ginger, A. Frick, N. V. DiPatrizio, K. Mackie, I. Katona, D. Piomelli and O. J. Manzoni. 2012. Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile x syndrome. Nature Communications 3: 1080.

Atwood, B. K., A. Straiker and K. Mackie. 2012. CB2 cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons. Neuropharmacology 63(4): 514-23.

Straiker, A., J. Wager-Miller, and K. Mackie. 2012. The CB1 cannabinoid receptor C-terminus regulates receptor desensitization in autaptic hippocampal neurones. Br J Pharmacol. 165(8): p. 2652-9.

Pickel, V. M., E. T. Shobin, D. A. Lane and K. Mackie. 2012. Cannabinoid-1 receptors in the mouse ventral pallidum are targeted to axonal profiles expressing functionally opposed opioid peptides and contacting N-acylphosphatidylethanolamine-hydrolyzing phospholipase D terminals. Neuroscience 227: 10-21.

Atwood, B.K., J. Wager-Miller, C. Haskins, A. Straiker, and K. Mackie. 2012. Functional selectivity in CB2 cannabinoid receptor signaling and regulation: implications for the therapeutic potential of CB2 ligands. Mol Pharmacol. 81(2): p. 250-63.

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.

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.

Ho, Y.C., H.J. Lee, L.W. Tung, Y.Y. Liao, S.Y. Fu, S.F. Teng, H.T. Liao, K. Mackie, and L.C. Chiou. 2011. Activation of orexin 1 receptors in the periaqueductal gray of male rats leads to antinociception via retrograde endocannabinoid (2-arachidonoylglycerol)-induced disinhibition. J Neurosci. 31(41): p. 14600-10.

Straiker, A., J. Wager-Miller, S.S. Hu, J.L. Blankman, B.F. Cravatt, and K. Mackie. 2011. COX-2 and fatty acid amide hydrolase can regulate the time course of depolarization-induced suppression of excitation. Br J Pharmacol. 164(6): p. 1672-83.

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. & K. Mackie. 2010. CB2 in neurons: A receptor with an identity crisis. Br. J. Pharmacol. 160:467-79.

Atwood, B.K. & K. Mackie. 2010. CB2 in neurons: A receptor with an identity crisis. Br. J. Pharmacol. 160:467-79.

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.

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.

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.

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.

Kellogg, R., K. Mackie & A. Straiker. 2009. Cannabinoid CB1 receptor-dependent long-term depression in autaptic excitatory neurons. J. Neurophysiol. 102:1160-1171.

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.

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.

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.

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.