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Annenberg Building Floor 19th Room 19-90 (Lab)
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Tel
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212-996-7214

Lakshmi A. Devi

PROFESSOR  Pharmacology and Systems Therapeutics
PROFESSOR  Psychiatry

Overview

Gender Female
E-mail lakshmi.devi@mssm.edu
Education and Training Ph.D., University of Windsor
  M.Sc., University of Mysore
  Postdoctoral Fellow, Vollum Institute
  Postdoctoral Fellow, Addiction Research Foundation

Dr. Devi is Professor of the Pharmacology and Systems Therapeutics and Psychiatry Departments. She is the Associate Dean for Academic Enhancement and Mentoring as well as Director of the Interdisciplinary Training in Drug Abuse Research Program.

Throughout her career, she has been interested in several lines of research, including receptor dimerization, regulation of peptide biosynthesis and opiate addiction. Part of her research focus is to explore mechanisms underlying opiate and cannabinoid receptor activation using a combination of molecular biological, biochemical, cell biological, pharmacological and behavioral techniques. Some of the projects in her lab also use a combination of classic and modern techniques in molecular pharmacology to explore the novel pharmacology of receptor heterodimers, and/or cutting-edge neuroproteomic techniques to analyze morphine induced changes in the levels of synaptic proteins and neuropeptides.

Devi Laboratory

Training

Education and Training Ph.D., University of Windsor
  M.Sc., University of Mysore
  Postdoctoral Fellow, Vollum Institute
  Postdoctoral Fellow, Addiction Research Foundation

Research

1.  Opioid receptor dimerization, pharmacology, and signaling

2.  Neuroendocrine peptide biosynthesis and processing

3.  Neuroproteomics of the synapse and opiate addiction

One of the research projects in the Devi Laboratory is focused on exploring the molecular mechanisms and the functional implications of opioid receptor dimerization. Opioid receptors are G protein-coupled receptors that are activated by opiate drugs such as morphine and heroin. Recently, we discovered that opioid receptors associate with each other and with other members of the G protein-coupled receptor family. This leads to changes in the pharmacological and signaling properties of the receptors, including ligand affinity, potency, and receptor trafficking. Thus, receptor-receptor interactions represent a novel mechanism for modulating opioid receptor function. We are currently investigating the physiological relevance of dimerization, as well as screening for drugs that target receptor heterodimers. Another research project is directed toward understanding the regulation of neuroendocrine peptide biosynthesis. Most neuroendocrine peptides, including opioid peptides, are synthesized from precursor proteins. Post-translational processing of these precursors is a key step in the production of biologically active peptides. We are studying the regulation of endopeptidases and exopeptidases involved in the biosynthesis of neuroendocrine peptides. In addition, using transgenic animals lacking processing enzymes, we are isolating and identifying novel neuropeptides. Studies to characterize the function of these peptides and their receptors are currently underway. The most recent project in the laboratory involves the use of cutting-edge neuroproteomic and neuropeptidomic techniques to study opiate addiction. Although chronic opiate use is known to produce long-lasting neural adaptations, the mechanisms underlying these changes are not well understood. We are using modern proteomic techniques (such as two-dimensional gel electrophoresis, differential isotopic labeling, and MS/MS sequencing) to analyze morphine-induced changes in the levels of synaptic proteins and neuropeptides. This approach will serve as a starting point to elucidating the molecular mechanisms underlying opiate addiction, as proteins/peptides that are altered by morphine treatment are likely to be involved in opiate-induced plasticity.

Publications

Abul-Husn NS, Bushlin I, Moron JA, Jenkins SL, Dolios G, Wang R, Iyengar R, Ma'ayan A, Devi LA. Systems approach to explore components and interactions in the presynapse. Proteomics 2009 June; 9(12): 3303-3315.


Ferre S, Baler R, Bouvier M, Caron MG, Devi LA, Durroux T, Fuxe K, George SR, Javitch JA, Lohse MJ, Mackie K, Milligan G, Pfleger KD, Pin JP, Volkow ND, Waldhoer M, Woods AS, Franco R. Building a new conceptual framework for receptor heteromers. Nat Chem Biol 2009 March; 5(3): 131-134.


Decaillot FM, Rozenfeld R, Gupta A, Devi LA. Cell surface targeting of mu-delta opioid receptor heterodimers by RTP4. Proc Natl Acad Sci U S A 2008 Oct; 105(41): 16045-16050.


Ellgren M, Artmann A, Tkalych O, Gupta A, Hansen HS, Hansen SH, Devi LA, Hurd YL. Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol 2008 Nov; 18(11): 826-834.


Gagnidze K, Sachchidanand , Rozenfeld R, Mezei M, Zhou MM, Devi LA. Homology modeling and site-directed mutagenesis to identify selective inhibitors of endothelin-converting enzyme-2. J Med Chem 2008 June; 51(12): 3378-3387.


Charlton JJ, Allen PB, Psifogeorgou K, Chakravarty S, Gomes I, Neve RL, Devi LA, Greengard P, Nestler EJ, Zachariou V. Multiple actions of spinophilin regulate mu opioid receptor function.. Neuron 2008 April; 58(2): 238-257.


Rozenfeld R, Devi LA. Regulation of CB1 cannabinoid receptor trafficking by the adaptor protein AP-3. FASEB J 2008 July; 22(7): 2311-2322.


Gupta A, Rozenfeld R, Gomes I, Raehal KM, Decaillot FM, Bohn LM, Devi LA. Post-activation-mediated changes in opioid receptors detected by N-terminal antibodies. J Biol Chem 2008 April; 283(16): 10735-10744.


Heimann AS, Gomes I, Dale CS, Pagano RL, Gupta A, de Souza LL, Luchessi AD, Castro LM, Giorgi R, Rioli V, Ferro ES, Devi LA. Hemopressin is an inverse agonist of CB1 cannabinoid receptors. Proc Natl Acad Sci U S A 2007 Dec; 104(51): 20588-20593.


Rozenfeld R, Devi LA. Receptor heterodimerization leads to a switch in signaling: beta-arrestin2-mediated ERK activation by mu-delta opioid receptor heterodimers. FASEB J 2007 Aug; 21(10): 2455-2465.


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