Lakshmi A. Devi
- ASSOCIATE DEAN FOR ACADEMIC ENHANCEMENT AND MENTORING
- PROFESSOR Pharmacology and Systems Therapeutics
- PROFESSOR Neuroscience
- PROFESSOR Psychiatry
M.Sc., University of Mysore
Ph.D., University of Windsor
Postdoctoral Fellowship, Addiction Research Foundation
Postdoctoral Fellowship, Vollum Institute
Dr. Devi is Professor of the Pharmacology and Systems Therapeutics, Psychiatry and Neuroscience 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.
For more information, please visit the Devi Laboratory website.
Research1. 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.
Gupta A, Mulder J, Gomes I, Rozenfeld R, Bushlin I, Ong E, Lim M, Maillet E, Junek M, Cahill CM, Harkany T, Devi LA. Increased abundance of opioid receptor heteromers after chronic morphine administration. Sci Signal 2010 Jul; 3(131): ra54.
Moron JA, Gullapalli S, Taylor C, Gupta A, Gomes I, Devi LA. Modulation of opiate-related signaling molecules in morphine-dependent conditioned behavior: Conditioned place preference to morphine induces CREB phosphorylation. Neuropsychopharmacology 2010 Mar; 35(4): 955-966.
Gomes I, Grushko JS, Golebiewska U, Hoogendoorn S, Gupta A, Heimann AS, Ferro ES, Scarlata S, Fricker LD, Devi LA. Novel endogenous peptide agonists of cannabinoid receptors. FASEB J 2009 Sep; 23(9): 3020-3029.
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.
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.
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.
Rozenfeld R, Devi LA. Regulation of CB1 cannabinoid receptor trafficking by the adaptor protein AP-3. FASEB J 2008 July; 22(7): 2311-2322.
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.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Devi did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
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