Ken Mackie | Faculty
Professor, Department of Psychological and Brain Sciences and Program in Neuroscience
Office: MSBII 120
- Brown University, ScB, Engineering, 1980
- Yale University, MD, 1984
- 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).
- 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.
- 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.
- 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.
- 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.
- Straiker, A., J. Wager-Miller, J. Hutchens, and K. Mackie. 2012. Differential signalling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurones. Br J Pharmacol. 165(8): p. 2660-71.
- 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.
- 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.
- 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.
- 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.
- 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.