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Dorit Ron, PhD

Dorit Ron, PhD
Associate Professor, Department of Neurology
Research Summary:

Signal transduction and neurobiology of addiction

The lab's main interest is in the molecular mechanisms underlying synaptic plasticity, and addiction. We use molecular biology, molecular pharmacology, and electrophysiology in parallel with behavioral models to study how scaffolding proteins and signaling complexes regulate neuronal functions such as that of the NMDA receptor, the growth factors BDNF and GDNF and neuronal gene expression. We then study how these normal processes are altered in the presence of acute or long-term exposure to ethanol, and how these lead to either the development or the prevention of alcohol addiction. Understanding how ethanol changes signaling cascades has and will continue to identify new potential drug targets.

 

Selected Publications

Logrip ML, Janak PH, Ron D., Escalating Ethanol Intake Is Associated With Altered Corticostriatal BDNF Expression . J. of Neurochemistry 2009, 109, 1459-1468.

Carnicella S, Ahmadianteherani S, Ron D. GDNF is an endogenous negative regulator of ethanol-mediated reward and of ethanol consumption after a period of deprivation. Alcoholism: Clinical and Experimental Research 2009, 33, 1-13.

Carnicella S, Ahmadiantherani S, He D-Y, Nielsen CK, Bartlett SE, Janak PH and Ron D.Cabergoline decreases alcohol drinking and seeking behaviors via GDNF. Biological Psychiatry, Feb 19, 2009 [Epub ahead of print].

Carnicella S,Yamamoto R, and Ron D. Excessive ethanol intake is reduced by GDNF. Alcohol 43:35-43, 2009.

Carnicella S and Ron D. GDNF a potential target to treat addiction? Pharmacology and Therapeutics,122, 9-18, 2009.

Rewal M, Jurd R, Gill MT, He D-Y, Ron D, Janak PH. Alpha4-Containing GABA-A Receptors in the Nucleus Accumbens Contribute to Moderate Intake of Alcohol. 2009, J Neurosci, 29, 543-9, 2009.

Grosso S, Volta V, Sala LA, Magri L, Vietri M, Marchisio PC, Ron D, Biffo S. PKCbII modulates translation independently from mTOR and through RACK1. Biochemical J 415:77-85, 2008.

Carnicella S, Kharazia V, Jeanblanc J, Janak PH and Ron D. GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse. PNAS 105:8114-9, 2008.

He D-Y and Ron D. GDNF reverses ethanol-mediated increases in tyrosine hydroxylase immunoreactivity via altering the activity of Hsp90. J. Biol. Chem. 283:12811-8, 2008.

Logrip ML, Janak PH and Ron D. Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake. FASEB J. 22:2393-404, 2008.

Jurd R, Thornton C ., Jun W, Luong K., Phamluong K, Kharazia V, and Ron D. Mind Bomb-2 is an E3 ligase that ubiquitinates the NMDA receptor NR2B subunit in a phosphorylation-dependent manner. J. Biol. Chem. 283:301-10, 2008.

Wang J, Carnicella S, Phamluong K, Jeanblanc J, Ronesi J, Chaudhri N, Janak PH, Lovinger DM and Ron D. Ethanol induces long-term facilitation of NR2B-NMDA receptor activity in the dorsal striatum: Implications for alcohol drinking behavior. J. Neurosci. 27:3593-602. 2007.

He D-Y, and Ron D, Autoregulation of glial cell line-derived neurotrophic factor expression: Implications for the long-lasting actions of the anti-addiction drug, Ibogaine. FASEB J. 20, E1820-7, 2006.

Schilström B, Yaka R, Suvarna N, Singh V, Ron D, Bonci A. Cocaine enhances NMDA currents in midbrain dopamine cells via redistribution of NMDA receptors. J. Neurosci. 26, 8549-58, 2006.

Kiely PA, O’Gorman D, Luong K, Ron D, O’Connor R. Insulin-like growth factor I controls a mutually exclusive association of RACK1 with protein phosphatase 2A and {beta}1 integrin to promote cell migration. Mol. Cell Biol. 26:4041-51, 2006.

Jeanblanc J, He D-Y, McGough NNH, Logrip ML, Phamluong K, Janak PH, Ron D. The Dopamine D3 receptor is part of a homeostatic pathway regulating ethanol consumption. J. Neurosci. 26:1457-64. 2006.

Janak PJ, Wolf F, Heberlein U, Pandey SC, Logrip ML, Ron D. BIG News In Alcohol Addiction: New findings on growth factor pathways BDNF, insulin, and GDNF. Alcoholism: Clin. Exp. Res. 30:214-21, 2006.

Ron D and Jurd R. The “ups and downs” of signaling cascades in addiction. Science STKE, 309, pp. re14, 2005.

Suvarna N, Wang J., Borgland S, Auberson YP, Bonci A, Ron D. Acute ethanol exposure alters functional NMDA receptor NR2 subunit ratio via H-Ras. J. Biol. Chem. 280:31450-9, 2005.

He D-Y, McGough NN, Ravindranathan A, Phamluong K, Janak PH, Ron D. The glial-derived neurotrophic factor mediates the desirable actions of the anti-addiction drug ibogaine. J. Neurosci. 25:619-28, 2005.

McGough NN, He D-Y, Logrip ML, Jeanblanc J, Phamluong K, Luong K, Kharazia V, Janak PH, Ron D. RACK1 and brain-derived neurotrophic factor: A homeostatis pathway that regulates alcohol addiction. J. Neurosci. 24:10542-52, 2004.

Thornton C, Tang K-C, Phamluong K, Luong K, Vagts A, Nikanjam D, Yaka R, Ron D. Spatial and temporal regulation of RACK1 function and N-methyl-D-aspartate receptor activity through WD40 motif-mediated dimerization. J. Biol. Chem. 279(30):31357-64, 2004.

Yaka R, Tang K-C, Camarini R, Ron D. Fyn kinase and NR2B containing NMDA receptors regulate acute ethanol sensitivity but not intake or conditioned reward. Alcoholism: Clin. Exp. Res. 27:1736-42, 2003..

Vagts AJ, He D-Y, Ron D. Cellular adaptation to chronic ethanol results in altered compartmentalization and function of the scaffolding protein RACK1. Alcoholism: Clin. Exp. Res. 27:1599-605, 2003.

Ungless M, Singh MV, Crowder TL, Yaka R, Ron D, Bonci A. Corticotropin-releasing factor (CRF) requires CRF-binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons. Neuron 39:401-7, 2003.

Thornton C, Yaka R, Dinh S, Ron D. Src tyrosine kinase activity is inhibited by H-Ras: Implications for the modulation of NMDA receptor trafficking. J. Biol. Chem. 278:23823-9, 2003.

Yaka R, Phamluong K, Ron D. Opposing activities of ethanol on selective population of NMDA receptors via Fyn phosphorylation, and RACK1 dissociation. J. Neurosci. 23:3623-32, 2003.

Yaka R, He D-Y, Phamluong K, Ron D. Pituitary adenylate cyclase activating polypeptide (PACAP(1-38)) enhances NMDA receptor function and BDNF expression via RACK1. J. Biol. Chem. 278:9630-8, 2003.

He D-Y, Vagts AJ, Yaka R, Ron D. Ethanol induces gene expression via the nuclear compartmentalization of RACK1. Mol. Pharmacol. 62(2):272-80, 2002.

Yaka R, Thornton C, Vagts AJ, Phamluong K, Bonci A, Ron D. NMDA-receptor function is regulated by the inhibitory scaffolding protein, RACK1. Proc. Natl. Acad. Sci. USA. 99:5710-5. 2002.

Ron D , Vagts AJ, Dohrman DP, Yaka R, Jiang Z, Yao L, Crabbe J, Grisel JE, Diamond I. Uncoupling of b IIPKC from its targeting protein RACK1 in response to ethanol in cultured cells and mouse brain. FASEB J. 14:2303-14, 2000.