Emiliana Borrelli

picture of Emiliana  Borrelli

Professor, Microbiology & Molecular Genetics
School of Medicine
Joint Appointment, Pharmacology
School of Medicine

Ph.D., University of Naples, 1979

Phone: (949) 824-3875, 46738
Fax: (949) 824-0074
Email: borrelli@uci.edu

University of California, Irvine
Microbiology and Molecular Genetics
308 Sprague Hall
Mail Code: 4049
Irvine, CA 92697
Research Interests
dopaminergic neurons, pharmacology, animal models, neurological and neuropsychiatric diseases
URLs
Academic Distinctions
Nomination to Member of the European Molecular Biology Organization (EMBO) (1997)
Prix de la Fondation de la Recherche Médicale, Paris (2001)
Prix Mercier-Bourdeix de l’Académie des Sciences Françaises (2001)
Prix INSERM in Physiopathology (2002)
Umesono Lecture Award, The Salk Institute (2014)
Chancellor’s Professor, University California Irvine, (2017)
Knight of the Legion of Honor, France (2017)
Golgi Award (2017)
IIC Los Angeles Creativity Award (2018)
Athalie Clarke Award (2018)
Research Abstract
Dopamine is a central neuromodulator of the CNS. Dysfunctions of dopaminergic homeostasis leading to either low or high dopamine levels are causally linked to Parkinson’s disease, schizophrenia, addiction and endocrine tumors. Studies conducted at the molecular, cellular and behavioral levels aim to uncover the molecular mechanisms by which dopamine receptor’s signaling controls neuronal functions and behavior. Genetically engineered mice (knock-out mice) constitute our experimental models in which we analyze how altered or abolished expression of dopamine receptors in specific neurons affects physiological responses. A particular interest is devoted to the analysis of dopamine-mediated effects on motor control and addiction to drugs of abuse. These studies are relevant to the understanding of human neurological and neuropsychiatric disorders.
Publications
Recent Publications:

Aoyama, S., Kase, H. and Borrelli, E. (2000) Rescue of Locomotor Impairment in Dopamine D2 Receptor Deficient Mice by an Adenosine A2A Receptor Antagonist. J. Neurosci., 20: 5848-5852.

Mathis, C., Hindelang, C., LeMeur, M. and Borrelli, E. (2000) A Transgenic Mouse Model for Inducible and Reversible Dysmyelination. J. Neurosci., 20: 7698-7705.

Bozzi, Y., Vallone, D. and Borrelli, E. (2000) Neuroprotective Role of Dopamine Against Hippocampal Cell Death. J. Neurosci., 20: 8643-8649.

Usiello, A., Baik, J. H., Rougé-Pont, F., Picetti, R., Dierich, A., LeMeur, M., Piazza, P. V. and Borrelli, E. (2000) Distinct Functions of the Two Isoforms of D2 Dopamine Receptors. Nature 408: 199-203.

Calabresi, P., Gubellini, P., Picconi, B., Centonze, D., Greengard, P., Hipskind, R., Borrelli, E., Bernardi, G. (2001) Inhibition of mitochondrial complex II induces a long-term potentiation of NMDA-mediated corticostriatal excitation requiring endogenous dopamine. J. Neurosci., 21: 5110-5120.

Bozzi, Y. and Borrelli, E. (2002) Dopamine D2 Receptors Signaling Controls Neuronal Cell Death Induced by Muscarinic and Glutamatergic Drugs. Mol. Cell. Neurosci. 19: 263-271.

Mathis, C., Denisenko-Nehrbass, N. , Girault J.-A., and Borrelli E. (2001) Essential Role of Oligodendrocytes in the Formation and Maintenance of Central Nervous System Nodal Regions. Development, 128: 4881-4890.

Caine, S.B., Negus, S.S., Mello, N.K.,. Patel, S. Bristow, L., Kulagowski, J., Vallone, D., Saiardi, A. and Borrelli, E. (2002) Role of dopamine D2 receptors in cocaine self-administration: studies with D2 receptor mutant mice and novel D2 receptor antagonist. J. Neurosci., 22 : 2977-2988.

Rougé-Pont, F., Usiello, A., Benoit-Marand, M., Gonon, F., Piazza, PV and Borrelli, E. Changes in extracellular dopamine induced by morphine and cocaine: Crucial Control by D2 receptors. (2002) J. Neurosci., 22: 3293-3301.

Iaccarino, C., Samad, T.A., Mathis, C., Kercret, H., Picetti, R.,and Borrelli, E. Control of Lactotroph Proliferation by Dopamine: Essential Role of Signalling Through D2 Receptors and ERKs. (2002) Proc.Natl. Acad. Sci. USA, 99:14530-5.

Centonze, D.,Grande,C, Usiello, A., Gubellini, P., Erbs, E., Martín, A.B., Pisani, A., Tognazzi, N., Bernardi, G., Moratalla, R., Borrelli, E., and Calabresi, P. Receptor Subtypes Involved in the Presynaptic and Postsynaptic Actions of Dopamine on Striatal Interneurons (2003) J. Neurosci, 23 6245-6254.

Lindgren N., Usiello A., Goiny M., Haycock J., Erbs E., Greengard P., Hökfelt T., Borrelli E. and Fisone G. Distinct roles of dopamine D2L and D2S receptor isoforms in the regulation of protein phosphorylation at presynaptic and postsynaptic sites. (2003) Proc. Natl. Acad. Sci. USA, 100: 4305-4309.

Mathis, C., Collin, L., and Borrelli, E. Oligodendrocyte ablation impairs cerebellum development. (2003) Development, 130: 4709-18.

Crosio C., Heitz E., Allis C.D., Borrelli E. and Sassone-Corsi P. Chromatin remodeling and neuronal response: multiple signaling pathways induce specific histone H3 modifications and early gene expression in hippocampal neurons. (2003) J Cell Sci. 116:4905-14.

Collin, L., Usiello, A., Erbs, E., Mathis, C. and Borrelli, E. Motor Training Compensates for Cerebellar Dysfunctions Caused by Oligodendrocyte Ablation. (2004) Proc. Natl. Acad. Sci. USA, 101:325-30.

Kobayashi M., Iaccarino C., Saiardi A., Heidt V., Bozzi Y., Picetti R., Vitale C., Westphal H., Drago J., and Borrelli E. Simultaneous absence of dopamine D1 and D2 receptor-mediated signaling is lethal in mice. Proc Natl Acad Sci U S A. (2004) 101:11465-70.

Centonze D., Usiello A., Costa C., Picconi B., Erbs, E., Bernardi G., Borrelli E. and Calabresi P. Chronic Haloperidol Promotes Corticostriatal Long-Term Potentiation by Targeting Dopamine D2L Receptors (2004) J.Neurosci. 24:8214-22.

Borrelli E. Without DJ-1, the D2 receptor doesn't play. (2005) Neuron 45:479-81.

Andersson M., Usiello A., Borgkvist A., Pozzi L., Dominguez C., Fienberg A.A., Svenningsson P., Fredholm B.B., Borrelli E., Greengard P., Fisone G. Cannabinoid action depends on phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons. (2005) J Neurosci. 25:8432-8.

Bozzi Y., Borrelli E. Dopamine in neurotoxicity and neuroprotection: what do D2 receptors have to do with it? (2006) Trends Neurosci. 29:167-74.

Yujnovsky I., Hirayama J., Doi M., Borrelli E., Sassone-Corsi P. Signaling mediated by the dopamine D2 receptor potentiates circadian regulation by CLOCK:BMAL1. (2006) Proc Natl Acad Sci U S A. 103: 6386-91.

Doi M., Yujnovsky I., Hirayama J., Malerba M., Tirotta E., Sassone-Corsi P., Borrelli E. Impaired light masking in dopamine D2 receptor-null mice. (2006) Nat Neurosci. 9: 732-734.

Welter M, Vallone D, Samad  A. T., Meziane H., Usiello A., and Borrelli E., Absence of dopamine D2 receptors unmasks an inhibitory control over the brain circuitries activated by cocaine. (2007) Proc Natl Acad Sci U S A. (2007)104:6840-5.

Tirotta E, Fontaine V, Picetti R, Lombardi M, Samad TA, Oulad-Abdelghani M, Edwards R, Borrelli E (2008) Signaling by dopamine regulates D2 receptors trafficking at the membrane. Cell Cycle 7:2241-2248.

Borrelli, E, Nestler,E.J. Allis, C.D., Sassone-Corsi, P. Decoding the Epigenetic Language of Neuronal Plasticity. (2008) Neuron, 60:961-974.

Bertolino A., Fazio L., Di Giorgio A., Blasi G., Romano R., Taurisano R., Caforio G., Sinibaldi L., Urini G., Popolizio T., Tirotta E., Papp A., Dallapiccola B., Borrelli E., Sadee W Genetically determined interaction between the dopamine transporter and the D2 receptor on prefronto-striatal activity and grey matter. J Neurosci. (2009) 29:1224-1234.

De Mei, C., Ramos, M., Iitaka, C., Borrelli, E. Getting specialized: presynaptic and postsynaptic dopamine D2 receptors. (2009) Curr. Opin. Pharmacol. 9:53-58.

Sahar S, Zocchi L, Kinoshita C, Borrelli E, Sassone-Corsi P. Regulation of BMAL1 protein stability and circadian function by GSK3beta-mediated phosphorylation. PLoS One. (2010) 5:e856.

Tirotta, E., De Mei, C., Iitaka, C., Ramos, M., Holmes, D., Borrelli, E. Unraveling the Role of Dopamine Receptors in vivo: Lessons from Knockout Mice. “The Dopamine Receptors, 2nd Edition”, Kim A Neve, Ed. Humana Press, Chapter 12

Benoit-Marand M., Ballion B., Borrelli E., Boraud T., Gonon F. Inhibition of dopamine uptake by D2 antagonists: an in vivo study. J. Neurochem. (2011) 116:449-58.

Fulton S, Thibault D, Mendez JA, Lahaie N, Tirotta E, Borrelli E, Bouvier M, Tempel BL, Trudeau LE. Contribution of Kv1.2 Voltage-gated Potassium channel to D2 autoreceptor regulation of axonal dopamine overflow. J. Biol. Chem. (2011) 286: 9360-72

Doretto S, Malerba M, Ramos M, Ikrar T, Kinoshita C, De Mei C, Tirotta E, Xu X, Borrelli E. Oligodendrocytes as regulators of neuronal networks during early postnatal development. (2011) PLoS One. 6:e19849.

Park E, Iaccarino C, Lee J, Kwon I, Baik SM, Kim M, Seong JY, Son GH, Borrelli E*, Kim K*. Regulatory roles of hnRNP M and Nova-1 in the alternative splicing of the dopamine D2 receptor pre-mRNA. J Biol Chem. (2011) 286:25301-8.

Anzalone A, Lizardi-Ortiz JE, Ramos M, De Mei C, Hopf FW, Iaccarino C, Halbout B, Jacobsen J, Kinoshita C, Welter M, Caron MG, Bonci A, Sulzer D, Borrelli E. Dual control of dopamine synthesis and release by pre- and postsynaptic dopamine D2 receptors. J Neurosci (2012) 32:9023-9034
 
Brami-Cherrier, K., Anzalone, A., Ramos, M., Forne, I., Macciardi, F., Imhof, A., Borrelli, E. Ablation of D2 autoreceptors causes epigenetic reprogramming of cortical neurons. Mol. Psychiatry (2014) 19(11):1153. PMID25346033
 
Maheux, J., St-Hilaire, M., Voyer, D., Tirotta, E., Borrelli, E., Rouillard, C., Rompré, P.P., Lévesque D. Dopamine (D2) antagonist-induced striatal Nurr77 expression requires activation of mGlu5 receptors by cortical afferents. Front Pharmacol. (2012) 3: 153
 
Radl,D., De Mei, C., Chen, E., Lee, H., Borrelli, E. Each individual isoform of the dopamine D2 receptor protects from lactotroph hyperplasia. (2013) Mol. Endocrinol. 27(6): 953-65
 
Viaro R, Calcagno M, Marti M, Borrelli E, Morari M. Pharmacological and genetic evidence for pre- and postsynaptic D2 receptor involvement in motor responses to nociception/orphanin FQ receptor ligands. Neuropharmacology. (2013) 72:126-38.
 
Upadhyay SK, Eckel-Mahan KL, Mirbolooki MR, Tjong I, Griffey SM, Schmunk G, Koehne A, Halbout B, Iadonato S, Pedersen B, Borrelli E, Wang PH, Mukherjee J, Sassone-Corsi P, Chandy KG. Selective Kv1.3 channel blocker as therapeutic for obesity and insulin resistance. Proc Natl Acad Sci U S A. (2013) 110:E2239-48.
 
Zhang Y, Wang C, Wang L, Parks GS, Zhang X, Guo Z, Ke Y, Li KW, Kim MK, Vo B, Borrelli E, Ge G, Yang L, Wang Z, Garcia-Fuster MJ, Luo ZD, Liang X, Civelli O. A novel analgesic isolated from a traditional chinese medicine. Curr. Biol. (2013) pii: S0960-9822 (13) 01494-2.
 
Brami-Cherrier, K., Anzalone, A., Ramos, M., Forne, I., Macciardi, F., Imhof, A., Borrelli, E. Epigenetic reprogramming of cortical neurons through alteration of dopaminergic circuits. Mol. Psychiatry (2014) 19(11):1193-200.
 
Kharkwal*, G., Brami-Cherrier*, K., Lizardi-Ortiz, J. E., Nelson, A. B., Ramos, M., Del Barrio, D., Sulzer, D., Kreitzer, A. C., Borrelli, E. Parkinsonism driven by antipsychotics originates from dopaminergic control of striatal cholinergic interneurons. Neuron (2016) 91 (1):67-78. PMID:27387649.
 
Kharkwal,G., Radl,D., Lewis, R., Borrelli, E. Dopamine D2 Receptors in Striatal Output Neurons Enable the Psychomotor Effects of Cocaine. Proc Natl Acad Sci U S A (2016) 113:11609-11614.
 
Urs, N. M., Gee, S. M., Pack, T. F., McCorvy, J. D., Evron, T., Snyder, J. C., Yang, X., Rodriguiz, R. M., Borrelli, E., Wetsel, W. C., Jin, J., Roth, B.L., O’Donnell, P., Caron, M.G.
Distinct cortico-striatal actions of ß-arrestin-biased dopamine D2 receptor signaling reveal determinants of in vivo functional selectivity. Proc Natl Acad Sci U S A (2016) 113(50):E8178-E8186. PMID: 27911814
 
Rose, S.J., Pack, T. F., Peterson S. M., Payne, K., Borrelli, E. Caron, M.G. Engineered D2R variants reveal the balanced and biased contributions of G-protein and ß-arrestin to dopamine-dependent functions. Neuropsychopharmacology (2017) doi:10.1038/npp.2017.254. PMID: 29068002
 
Robinson B.G., Condon A.F., Radl D., Borrelli E., Williams J.T., Neve K.A. Cocaine-induced adaptation of dopamine D2S, but not D2L autoreceptors. Elife (2017) 6. pii: e31924. doi:10.7554/eLife.31924
 
Dyar KA, Lutter D, Artati A, Ceglia NJ, Liu Y, Armenta D, Jastroch M, Schneider S, de Mateo S, Cervantes M, Abbondante S, Tognini P, Orozco-Solis R, Kinouchi K, Wang C, Swerdloff R, Nadeef S, Masri S, Magistretti P, Orlando V, Borrelli E, Uhlenhaut NH, Baldi P, Adamski J, Tschöp MH, Eckel-Mahan K, Sassone-Corsi P. Atlas of Circadian Metabolism reveals system-wide coordination and communication between clocks. Cell (2018) 174:1571-1585. PMID: 30193114
 
Scheggia D, Mastrogiacomo R, Mereu M, Sannino S, Straub RE, Armando M, Managò F, Guadagna S, Piras F, Zhang F, Kleinman JE, Hyde TM, Kaalund SS, Pontillo M, Orso G, Caltagirone C, Borrelli E, De Luca MA, Vicari S, Weinberger DR, Spalletta G, Papaleo F. Variation in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment. Nat. Comm. (2018) 9:2265 PMID: 29891954
 
Radl, D., Chiacchiaretta, M., Lewis, R.G., Brami-Cherrier, K., Arcuri, L., Borrelli, E. Differential regulation of striatal motor behavior and related cellular responses by dopamine D2L and D2S isoforms. Proc Natl Acad Sci U S A (2018) 115:198-203. PMID:29255027
Professional Societies
American Society for Neuroscience
French Society for Neuroscience
European Molecular Biology Organization (EMBO member)
Graduate Programs
Cellular and Molecular Biosciences

Interdepartmental Neuroscience Program

Medicinal Chemistry and Pharmacology

Pharmacological Sciences

Research Center
Center for Epigenetics and Metabolism
Last updated
11/14/2019