Nikhil Urs, Ph.D.
Dopamine (DA) is a catecholamine neurotransmitter found in the mammalian brain and regulates many critical physiological processes such as movement, cognition, motivation, reward/pleasure, and hormone regulation. Dysfunction of the dopamine system has been implicated in many brain disorders, including Parkinson’s disease (PD), schizophrenia, OCD, and ADHD. The goal of our laboratory is to study the role of genetic and environmental factors on dopamine neurotransmission and to learn more about the dopamine system by deciphering, a) signaling pathways involved in DA neurotransmission, b) functional dopamine neuronal circuits, and c) how these integrate and manifest behaviorally in an organism (mouse). Using these integrated approaches—in parallel—will allow us to fine-tune dopamine neurotransmission and devise novel drug- and gene-based therapeutic approaches to treat dopamine-related disorders such as PD and schizophrenia.
- Toth K, Slosky LM, Pack TF, Urs NM, Boone P, Mao L, Abraham D, Caron MG, Barak LS. Ghrelin receptor antagonism of hyperlocomotion in cocaine-sensitized mice requires βarrestin-2. Synapse. 2018 Jan;72(1). doi: 10.1002/syn.22012. Epub 2017 Oct 7.\
- Zhu L, Rossi M, Cui Y, Lee RJ, Sakamoto W, Perry NA, Urs NM, Caron MG, Gurevich VV, Godlewski G, Kunos G, Chen M, Chen W, Wess J. Hepatic β-arrestin 2 is essential for maintaining euglycemia. J Clin Invest. 2017 Aug 1;127(8):2941-2945. doi: 10.1172/JCI92913. Epub 2017 Jun 26.
- Zhu L, Almaça J, Dadi PK, Hong H, Sakamoto W, Rossi M, Lee RJ, Vierra NC, Lu H, Cui Y, McMillin SM, Perry NA, Gurevich VV, Lee A, Kuo B, Leapman RD, Matschinsky FM, Doliba NM, Urs NM, Caron MG, Jacobson DA, Caicedo A, Wess J. β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions. Nat Commun. 2017 Feb 1;8:14295. doi: 10.1038/ncomms14295.
- Urs NM, Gee SM, Pack TF, McCorvy JD, Evron T, Snyder JC, Yang X, Rodriguiz RM, Borrelli E, Wetsel WC, Jin J, Roth BL, O’Donnell P, Caron MG. Distinct cortical and striatal actions of a β-arrestin-biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):E8178-E8186. Epub 2016 Dec 1.
- Urs NM, Peterson SM, Caron MG. New Concepts in Dopamine D(2) Receptor Biased Signaling and Implications for Schizophrenia Therapy. Biol Psychiatry. 2017 Jan 1;81(1):78-85. doi: 10.1016/j.biopsych.2016.10.011. Epub 2016 Oct 19. Review.
- Barak LS, Bai Y, Peterson S, Evron T, Urs NM, Peddibhotla S, Hedrick MP, Hershberger P, Maloney PR, Chung TD, Rodriguiz RM, Wetsel WC, Thomas JB, Hanson GR, Pinkerton AB, Caron MG. ML314: A Biased Neurotensin Receptor Ligand for Methamphetamine Abuse. ACS Chem Biol. 2016 Jul 15;11(7):1880-90. doi: 10.1021/acschembio.6b00291. Epub 2016 May 5.