Our research focuses on signal transduction and epigenetic mechanisms underlying CNS disorders and their treatment. We use advanced genetic mouse models, viral mediated gene transfer and multidisciplinary approaches to understand the network and cell type-specific mechanisms of chronic pain, addiction, stress, and depression. Current projects investigate the mechanism by which signal transduction complexes modulate drug addiction and chronic stress, and the role of signal transduction and epigenetic complexes in the transition to chronic pain states. Another line of research investigates the intracellular pathways in the brain reward center involved affective and sensory components of chronic pain. We aim to understand gene expression adaptations in response to peripheral nerve injury or inflammation throughout the pain matrix, and to develop novel therapeutic avenues for chronic pain conditions. We focus on five major research areas:
- Molecular mechanisms of drug addiction in pain-free and chronic pain states
- Targeting regulators of G protein signaling (RGS proteins) in the brain and heart to prevent maladaptive responses to chronic stress
- Novel intracellular targets for the treatment of chronic pain
- Epigenetic mechanisms of chronic pain
- The role of the brain reward center in sensory and affective neuropathic pain symptoms and treatment efficacy
drug addiction, depression, chronic pain, nociception, neuropathic pain, genetic mouse models, viral gene transfer, analgesics, opioid analgesia, opioid dependence, molecular biology, protein complexes, G protein coupled receptors, transcriptional regulation, epigenetics
Striatal Rgs4 regulates feeding and susceptibility to diet-induced obesity.
Michaelides M, Miller ML, Egervari G, Primeaux SD, Gomez JL, Ellis RJ, Landry JA, Szutorisz H, Hoffman AF, Lupica CR, Loos RJF, Thanos PK, Bray GA, Neumaier JF, Zachariou V, Wang GJ, Volkow ND, Hurd YL.
Mol Psychiatry. 2018 Jun 28. doi: 10.1038/s41380-018-0120-7.
Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt/β-catenin pathway.
Gaspari S, Purushothaman I, Cogliani V, Sakloth F, Neve RL, Howland D, Ring RH, Ross EM, Shen L, Zachariou V.
Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):E2085-E2094. doi: 10.1073/pnas.1707887115. Epub 2018 Feb 12.
Effective Attenuation of Adenosine A1R Signaling by Neurabin Requires Oligomerization of Neurabin.
Chen Y, Booth C, Wang H, Wang RX, Terzi D, Zachariou V, Jiao K, Zhang J, Wang Q.
Mol Pharmacol. 2017 Dec;92(6):630-639. doi: 10.1124/mol.117.109462. Epub 2017 Sep 27.
Brain-Derived Neurotrophic Factor in the Mesolimbic Reward Circuitry Mediates Nociception in Chronic Neuropathic Pain.Zhang H, Qian YL, Li C, Liu D, Wang L, Wang XY, Liu MJ, Liu H, Zhang S, Guo XY, Yang JX, Ding HL, Koo JW, Mouzon E, Deisseroth K, Nestler EJ, Zachariou V, Han MH, Cao JL. Biol Psychiatry. 2017 Mar 1. pii: S0006-3223(17)31353-7. doi: 10.1016/j.biopsych.2017.02.1180. [Epub ahead of print] PMID:28390647
Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression.Descalzi G, Mitsi V, Purushothaman I, Gaspari S, Avrampou K, Loh YE, Shen L, Zachariou V.Sci Signal. 2017 Mar 21;10(471). pii: eaaj1549. doi: 10.1126/scisignal.aaj1549.PMID:28325815
RGS9-2 Modulates Responses to Oxycodone in Pain-Free and Chronic Pain States. Gaspari S, Cogliani V, Manouras L, Anderson EM, Mitsi V, Avrampou K, Carr FB, Zachariou V.Neuropsychopharmacology. 2017 Jun;42(7):1548-1556. doi: 10.1038/npp.2017.4. Epub 2017 Jan 11.PMID:28074831
Modulation of pain, nociception, and analgesia by the brain reward center. Mitsi V, Zachariou V.Neuroscience. 2016 Dec 3;338:81-92. doi: 10.1016/j.neuroscience.2016.05.017. Epub 2016 May 14. Review. PMID:27189881
Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior.Gacias M, Gaspari S, Santos PM, Tamburini S, Andrade M, Zhang F, Shen N, Tolstikov V, Kiebish MA, Dupree JL, Zachariou V, Clemente JC, Casaccia P.Elife. 2016 Apr 20;5. pii: e13442. doi: 10.7554/eLife.13442.PMID:27097105
Mitsi V, Terzi D, Purushothaman I, Manouras L, Gaspari S, Neve RL, Stratinaki M, Feng J, Shen L, Zachariou V. RGS9-2–controlled adaptations in the striatum determine the onset of action and efficacy of antidepressants in neuropathic pain states. Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):E5088-97.
Descalzi G, Ikegami D, Ushijima T, Nestler EJ, Zachariou V, Narita M. Epigenetic mechanisms of chronic pain. Trends Neurosci. 2015 Apr;38(4):237-46.
Caldarone BJ, Zachariou V, King SL. Rodent models of treatment-resistant depression. Eur J Pharmacol. 2015 Apr 15;753:51-65.
Terzi D, Gaspari S, Manouras L, Descalzi G, Mitsi V, Zachariou V. RGS9-2 modulates sensory and mood related symptoms of neuropathic pain. Neurobiol Learn Mem. 2014 Nov;115:43-8.
Carr FB, Zachariou V. Nociception and pain: lessons from optogenetics. Front Behav Neurosci. 2014 Mar 25;8:69
Gaspari S, Papachatzaki MM, Koo JW, Carr FB, Tsimpanouli ME, Stergiou E, Bagot RC, Ferguson D, Mouzon E, Chakravarty S, Deisseroth K, Lobo MK, Zachariou V. Nucleus accumbens-specific interventions in RGS9-2 activity modulate responses to morphine. Neuropsychopharmacology. 2014 Jul;39(8):1968-77
Stratinaki M, Varidaki A, Mitsi V, Ghose S, Magida J, Dias C, Russo SJ, Vialou V, Caldarone BJ, Tamminga CA, Nestler EJ, Zachariou V. Regulator of G protein signaling 4 is a crucial modulator of antidepressant drug action in depression and neuropathic pain models. Proc Natl Acad Sci U S A. 2013 May 14;110(20):8254-9.
Sun H, Maze I, Dietz DM, Scobie KN, Kennedy PJ, Damez-Werno D, Neve RL, Zachariou V, Shen L, Nestler EJ. Morphine epigenomically regulates behavior through alterations in histone H3 lysine 9 dimethylation in the nucleus accumbens. J Neurosci. 2012 Nov 28;32(48):17454-64.
Waugh JL, Celver J, Sharma M, Dufresne RL, Terzi D, Risch SC, Fairbrother WG, Neve RL, Kane JP, Malloy MJ, Pullinger CR, Gu HF, Tsatsanis C, Hamilton SP, Gold SJ, Zachariou V, Kovoor A. Association between regulator of G protein signaling 9-2 and body weight. PLoS One. 2011;6(11):e27984.
Terzi D, Cao Y, Agrimaki I, Martemyanov KA, Zachariou V. R7BP modulates opiate analgesia and tolerance but not withdrawal. Neuropsychopharmacology. 2012 Mar;37(4):1005-12.
Psifogeorgou K, Terzi D, Papachatzaki MM, Varidaki A, Ferguson D, Gold SJ, Zachariou V. A unique role of RGS9-2 in the striatum as a positive or negative regulator of opiate analgesia. J Neurosci. 2011 Apr 13;31(15):5617-24.
Han MH, Renthal W, Ring RH, Rahman Z, Psifogeorgou K, Howland D, Birnbaum S, Young K, Neve R, Nestler EJ, Zachariou V. Brain region specific actions of regulator of G protein signaling 4 oppose morphine reward and dependence but promote analgesia. Biol Psychiatry. 2010 Apr 15;67(8):761-9.
Traynor JR, Terzi D, Caldarone BJ, Zachariou V. RGS9-2: probing an intracellular modulator of behavior as a drug target. Trends Pharmacol Sci. 2009 Mar;30(3):105-11.
Terzi D, Stergiou E, King SL, Zachariou V. Regulators of G protein signaling in neuropsychiatric disorders. Prog Mol Biol Transl Sci. 2009;86:299-333.
Krishnan V, Graham A, Mazei-Robison MS, Lagace DC, Kim KS, Birnbaum S, Eisch AJ, Han PL, Storm DR, Zachariou V, Nestler EJ. Calcium-sensitive adenylyl cyclases in depression and anxiety: behavioral and biochemical consequences of isoform targeting. Biol Psychiatry. 2008 Aug 15;64(4):336-43.
Multiple actions of spinophilin regulate mu opioid receptor function. Charlton JJ, Allen PB, Psifogeorgou K, Chakravarty S, Gomes I, Neve RL, Devi LA, Greengard P, Nestler EJ, Zachariou V. Neuron. 2008 Apr 24;58(2):238-47.
Meet the Team
MD PhD student
Visiting Graduate Student
Pedicatric Resident Physician
Commonly used antidepressant drugs change levels of a key signaling protein in the brain region that processes both pain and mood, according to a new study. “Our data reveals that antidepressants that target specific neurotransmitters in the brain, particularly TCAs and SNRIs, regulate chronic pain and depression-related symptoms through actions in the nucleus accumbens,” said Venetia Zachariou, PhD, Associate Professor in the Fishberg Department of Neuroscience and the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai.
Brain protein promotes maintenance of chronic pain
Chronic pain and depression are inked by gene changes in the brain
Oxycodone actions under chronic pain states
Long term neuropathic pain promotes the expression of genes associated with depression
Antidepressants Fine Tune the reward pathway to lessen symptoms of neuropathic pain
Science and Pain CUNY Television
Antidepressants alter signaling protein in the Nucleus accumbens to reduce Neuropathic pain
Pathways activated by antidepressants in the brain reward center alleviate depression and nerve pain