Kenneth Mackie

Brown University, ScB, Engineering, 1980
Yale University, MD, 1984
Post-doctoral fellowship, 1984-1986, Advisor—Paul Greengard
Internship (Internal Medicine) Yale University, 1986-1987
Residency (Anesthesiology) University of Washington, 1987-1990
Post-doctoral fellowship, 1990-1992, Advisor—Bertil Hille

Research Interests

Areas of study/research topics:
Regulation of CB1 cannabinoid receptor signaling
Regulation of endocannabinoid production
Role of endocannabinoids in synaptic plasticity
Novel cannabinoid receptors

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

Harkany, T., Guzman, M., Galve-Roperh, I., Berghuis, P., Devi, L.A., and Mackie, K. (2007). The emerging functions of endocannabinoid signaling during CNS development. Trends Pharmacol Sci. 28(2): 83-92.

Duarte, J.M., Nogueira, C., Mackie, K., Oliveira, C.R., Cunha, R.A., and Kofalvi, A. (2007). Increase of cannabinoid CB(1) receptor density in the hippocampus of streptozotocin-induced diabetic rats. Exp Neurol. 204(1): 479-484.

Deshmukh, S., Onozuka, K., Bender, K.J. Bender, V.A., Lutz, B., Mackie, K., and Feldman, D.E. (2007). Postnatal development of cannabinoid receptor type 1 expression in rodent somatosensory cortex. Neuroscience, 145(1): 279-87.

Chen, K., Neu, A., Howard, A.L., Foldy, C., Echegoyen, J., Hilgenberg, L., Smith, M., Mackie, K., and Soltesz, I. (2007). Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures. J Neurosci., 27(1): 46-58.

Fu, J., Astarita, G., Gaetani, S., Kim, J. Cravatt, B.F., Mackie, K., and Piomelli, D. (2007). Food intake regulates oleoylethanolamide formation and degradation in the proximal small intestine. J Biol Chem., 282(2): 1518-1528.

Oropeza, V.C., Mackie, K., and Van Bockstaele, E.J. (2007). Cannabinoid receptors are localized to noradrenergic axon terminals in the rat frontal cortex. Brain Res., 1127(1): 36-44.

Freeman, G.J., Mackie, K.M., Sare, J., Walsh, A.K., and Pherwani, A.D. (2006). A novel approach to the management of the diabetic foot: metatarsal excision in the treatment of osteomyelitis. Eur J Vasc Endovasc Surg., 33(2): 217-219.

Straiker, A. and Mackie, K. (2006). Metabotropic suppression of excitation in autaptic hippocampal neurons. J Physiol., Nov 16; [Epub ahead of print]

Cenni, G., Blandina, P., Mackie, K., Nosi, D., Formigli, L., Giannoni, P., Ballini, C., Della Corte, L., Francesco Mannaioni, P., and Beatrice Passani, M. (2006). Differential effect of cannabinoid agonists and endocannabinoids on histamine release from distinct regions of the rat brain. Eur J Neurosci., 24(6): 1633-1644.

Dzavik, V., Kharbanda, R., Ivanov, J., Ing, D.J., Bui, S., Mackie, K., Ramsamujh, R., Barolet, A., Schwartz, L., and Seidelin, P.H. (2006). Predictors of long-term outcome after crush stenting of coronary bifurcation lesions: importance of the bifurcation angle. Am Heart J., 152(4): 762-769.

Monory, K., Massa, F., Egertova, M., Eder, M., Blaudzun, H., Westenbroek, R., Kelsch, W., Jacob, W., Marsch, R., Ekker, M., Long, J., Rubenstein, J.L., Goebbels, S., Nave, K.A., During, M., Klugmann, M., Wolfel, B., Dodt, H.U., Zieglgansberger, W., Wotjak, C.T., Mackie, K., Elphick, M.R., Marsicano, G., and Lutz, B. (2006). The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron, 51(4): 455-466.

Mitrirattanakul, S., Ramakul, N., Guerrero, A.V., Matsuka, Y., Ono, T., Iwase, H., Mackie, K., Faull, K.F., and Spigelman, I. (2006). Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain. Pain, 126(1-3): 102-114.

Schuchmann, S., Schmitz, D., Rivera, C., Vanhatalo, S., Salmen, B., Mackie, K., Sipila, S.T., Voipio, J., and Kaila, K. (2006). Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis. Nat Med., 12(7): 817-823.

Mackie, K. and Stella, N. (2006). Cannabinoid receptors and endocannabinoids: evidence for new players. AAPS J., 8(2): E298-E306. Review.

Straiker, A. and Mackie, K. (2006). Cannabinoids, electrophysiology, and retrograde messengers: challenges for the next 5 years. AAPS J., 8(2): E272-E276. Review.

Tam, J., Ofek, O., Fride, E., Ledent, C., Gabet, Y., Muller, R., Zimmer, A., Mackie, K., Mechoulam, R., Shohami, E., Bab, I. (2006). Involvement of neuronal cannabinoid receptor CB1 in regulation of bone mass and bone remodeling. Mol Pharmacol., 70(3): 786-92.

. Katona, I., Urban, G.M., Wallace, M., Ledent, C., Jung, K.M., Piomelli, D., Mackie, K., and Freund, T.F. (2006). Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci., 26(21): 5628-5637.

Cobellis, G., Cacciola, G., Scarpa, D., Meccariello, R., Chianese, R., Franzoni, M.F., Mackie, K., Pierantoni, R., and Fasano, S. (2006). Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells. Biol Reprod., 75(1): 82-89.

Mackie K. (2005). Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol., 168: 299-325. Review.

Mackie, K. (2006). Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength. Int J Obes (Lond)., 30 Suppl 1: S19-23. Review.

Pickel, V.M., Chan, J., Kearn, C.S., and Mackie, K. (2006). Targeting dopamine D2 and cannabinoid-1 (CB1) receptors in rat nucleus accumbens. J Comp Neurol., 495(3): 299-313.

Mackie, K. (2006). Cannabinoid receptors as therapeutic targets. Annu Rev Pharmacol Toxicol., 46: 101-122. Review.

Matyas, F., Yanovsky, Y., Mackie, K., Kelsch, W., Misgeld, U., and Freund, T.F. (2006). Subcellular localization of type 1 cannabinoid receptors in the rat basal ganglia. Neuroscience, 137(1): 337-361.

Lauckner, J.E., Hille, B., and Mackie, K. (2005). The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins. Proc Natl Acad Sci U S A., 102(52): 19144-19149.

Berghuis,P., Dobszay, M.B., Wang, X., Spano, S., Ledda, F., Sousa, K.M., Schulte, G., Ernfors, P., Mackie, K., Paratcha, G., Hurd, Y.L., and Harkany, T. (2005). Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor. Proc Natl Acad Sci U S A., 102(52): 19115-19120.

. Nyiri, G., Cserep, C., Szabadits, E., Mackie, K., and Freund, T.F. (2005). CB1 cannabinoid receptors are enriched in the perisynaptic annulus and on preterminal segments of hippocampal GABAergic axons. Neuroscience, 136(3): 811-822.

Osei-Hyiaman, D., Depetrillo, M., Harvey-White, J., Bannon, A.W., Cravatt, B.F., Kuhar, M.J., Mackie, K., Palkovits, M., and Kunos, G. (2005). Cocaine- and amphetamine-related transcript is involved in the orexigenic effect of endogenous anandamide. Neuroendocrinology, 81(4): 273-282.