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

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.