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George Kunos, M.D., Ph.D., Senior Investigator

Dr. Kunos received his M.D. degree in 1966 from Semmelweis University in Budapest and his Ph.D. in 1973 from McGill University in Montreal where he worked with Mark Nickerson on adrenergic receptors. In 1974 he joined the faculty in Pharmacology and Medicine at McGill University and then in 1987 joined the NIAAA as Chief of the Laboratory of Physiologic and Pharmacologic Studies. Dr. Kunos moved to the Medical College of Virginia in 1992 to Chair the Department of Pharmacology & Toxicology. In 2000 he returned to NIH as Scientific Director of NIAAA. He is an elected fellow of the High Blood Pressure Research Council of the American Heart Association and a foreign member of the Hungarian Academy of Sciences. He is recipient of the Mechoulam Award of the Intl. Cannabinoid Research Society and the NIH Director's Award. Dr. Kunos' laboratory is studying the role of endocannabinoids in neuroendocrine, metabolic and cardiovascular regulation.
Photo of George Kunos, M.D., Ph.D., Senior Investigator


Research Interests:
Our laboratory is interested in the biology of the endocannabinoid (EC) system, with particular focus on its role in cardiovascular and metabolic regulation and the related therapeutic implications.

ECs are lipid mediators that interact with the same cannabinoid receptors - CB1 or CB2 - that recognize the psychoactive ingredient of marijuana and produce similar biological effects. We discovered that macrophage-derived ECs acting via vascular and cardiac CB1 receptors contribute to the hypotension in various forms of shock and advanced liver cirrhosis, and also act as a compensatory mechanism in hypertension. We have also identified a novel, nonCB1/nonCB2 GPCR that mediates the vasodilator effect of ECs in certain vascular beds. We use physiological approaches in whole animals, including genetically altered mice, as well as cell and molecular biological techniques.

We discovered that ECs acting via CB1 receptors regulate appetite in a leptin-dependent manner and also regulate the desire to drink alcohol. ECs also regulate peripheral fat metabolism via CB1 receptors in liver and adipose tissue, and these peripheral effects contribute to diet-induced obesity (DIO) and its hormonal/metabolic consequences. ECs acting via hepatic CB1 receptors also play a key role in alcoholic liver disease and in liver regeneration. The emerging role of peripheral CB1 receptors led us to develop and test novel CB1 blockers - both neutral antagonists and inverse agonists - that do not penetrate the brain. We found that such compounds reverse DIO and the associated fatty liver, dyslipidemia and insulin and leptin resistance without causing unwanted behavioral effects that limit the therapeutic potential of brain-penetrant CB1 antagonists. A novel, peripheral CB1 inverse agonist is currently undergoing toxicological screening in preparation to its clinical testing. Recently, we have developed a new class of dual target compounds that act as peripheral CB1 antagonist and also act to inhibit inducible NO synthase or activate AMP kinase, and found that such dual target compounds have superior antifibrotic efficacy over traditional CB1 antagonists.

Selected Recent Publications:
  • Jourdan T, Godlewski G, Cinar R, Bertola A, Szanda G, Liu J, Tam J, Han T, Mukhopadhyay B, Skarulis MC, Ju C, Aouadi M, Czech MP, Kunos G (2013) Endocannabinoid-activated Nlrp3 inflammasome in infiltrating macrophages mediates β-cell loss in type 2 diabetes., Nature Medicine 19, 1132-1140. Full Text/Abstract

  • Liu J, Cinar R, Xiong K, Lin Y, Godlewski G, Ntambi JM, Kunos G (2013) Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase., Proc Natl Acad Sci USA 110, 18832-18837. Full Text/Abstract

  • Tam J, Cinar R, Liu J, Godlewski G, Wesley D, Jourdan T, Szanda G, Mukhopadhyay B, Chedester L, Liow J-S, Innis RB, Rice KC, Deschamps JR, Chorvat RJ, McElroy JF, Kunos G (2012) Peripheral CB1 receptor inverse agonism reduces obesity by reversing leptin resistance., Cell Metabolism 16, 167-179.

  • Liu J, Zhou L, Xiong K, Godlewski G, Mukhopadhyay B, Tam J, Yin S, Gao P, Shan X, Pickel J, Bataller R, O'Hare J, Scherer T, Buettner C, Kunos G (2012) Hepatic cannabinoid receptor-1 mediates diet-induced insulin resistance via inhibition of insulin signaling and clearance in mice., Gastroenterology 142, 1218-1228. Full Text/Abstract

  • Mukhopadhyay B, Cinar R, Yin S, Liu J, Tam J, Godlewski G, Harvey-White J, Mordi I, Cravatt BF, Lotersztajn S, Gao B, Yuan Q, Schuebel K, Goldman D, Kunos G (2011) Hyperactivation of anandamide synthesis and regulation of cell-cycle progression via cannabinoid type 1 (CB1) receptors in the regenerating liver, Proc Natl Acad Sci USA 108, 6323-6328.

  • Tam J, Vemuri VK, Liu J, Batkai S, Mukhopadhyay B, Godlewski G, Osei-Hyiaman D, Ohnuma S, Ambudkar SV, Pickel J, Makriyannis A, Kunos G (2010) peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity, Journal of Clinical Investigation 120, 2953-2966.

  • Godlewski G, Alapafuja SO, Batkai S, Nikas SP, Cinar R, Offertaler L, Osei-Hyiaman D, Liu J, Mukhopadhyay B, Harvey-WhiteJ, Tam J, Pacak K, Blankman JL, Cravatt BF, Makriyannis A, Kunos G (2010) Inhibitor of fatty acid amide hydrolase normalizes cardiovascular function in hypertension without adverse metabolic effects, Chemistry & Biology 17, 1256-1266.

All Selected Publications

Contact Information:

Dr. George Kunos
Neuroendocrinology Section
Laboratory of Physiologic Studies, NIAAA
5625 Fishers Lane
Rm. 2S24, MSC 9413
Bethesda, MD 20892-9413

Telephone: (301) 443-2069 (office), (301) 443-2069 (laboratory), (301) 480-0257 (fax)


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