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Lakshmi Devi

  • DEAN FOR ACADEMIC DEVELOPMENT AND ENRICHMENT
  • PROFESSOR Pharmacology and Systems Therapeutics
  • PROFESSOR Neuroscience
  • PROFESSOR Psychiatry
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Education

  • M.Sc., University of Mysore

  • Ph.D., University of Windsor

  • Postdoctoral Fellowship, Addiction Research Foundation

  • Postdoctoral Fellowship, Vollum Institute

Biography

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

Gupta A, Gomes I, Wardman J, Devi LA. Opioid Receptor Function is Regulated by Post-endocytic Peptide Processing. Journal of Biological Chemistry 2014 May;(pii: jbc.M113.537704).

Stockton SD, Devi LA. An integrated quantitative proteomics and systems biology approach to explore synaptic protein profile changes during morphine exposure. Neuropsychopharmacology 2014 Jan; 39(1).

Gomes I, Aryal DK, Wardman JH, Gupta A, Gagnidze K, Rodriguiz RM, Kumar S, Wetsel WC, Pintar JE, Fricker LD, Devi LA. GPR171 is a hypothalamic G protein-coupled receptor for BigLEN, a neuropeptide involved in feeding. Proc Natl Acad Sci USA 2013 Oct; 110(40).

Gomes I, Fujita W, Gupta A, Saldanha AS, Negri A, Pinello CE, Roberts E, Filizola M, Hodder P, Devi LA. Identification of a μ-δ opioid receptor heteromer-biased agonist with antinociceptive activity. Proc Natl Acad Sci USA 2013 Jul; 110(29).

Bushlin I, Gupta A, Stockton SD, Miller LK, Devi LA. Dimerization with cannabinoid receptors allosterically modulates delta opioid receptor activity during neuropathic pain. PLoS One 2012; 7(12).

Filizola M, Devi LA. Structural biology: How opioid drugs bind to receptors. Nature 2012 May; 485(7398).

Rozenfeld R, Bushlin I, Gomes I, Tzavaras N, Gupta A, Neves S, Battini L, Gusella GL, Lachmann A, Ma'ayan A, Blitzer RD, Devi LA. Receptor heteromerization expands the repertoire of cannabinoid signaling in rodent neurons. PLoS One 2012; 7(1).

Abul-Husn NS, Annangudi SP, Ma'ayan A, Ramos-Ortolaza DL, Stockton SD, Gomes I, Sweedler JV, Devi LA. Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis. PLoS One 2011; 6(10).

Miller LK, Hou X, Rodriguiz RM, Gagnidze K, Sweedler JV, Wetsel WC, Devi LA. Mice deficient in endothelin-converting enzyme-2 exhibit abnormal responses to morphine and altered peptide levels in the spinal cord. Journal of Neurochemistry 2011 Dec; 119(5).

Rozenfeld R, Gupta A, Gagnidze K, Lim MP, Gomes I, Lee-Ramos D, Nieto N, Devi LA. AT1R-CB₁R heteromerization reveals a new mechanism for the pathogenic properties of angiotensin II. EMBO Journal 2011 Jun; 30(12).

Gomes I, Ijzerman AP, Ye K, Maillet EL, Devi LA. G protein-coupled receptor heteromerization: a role in allosteric modulation of ligand binding. Molecular Pharmacology 2011 Jun; 79(6).

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. Science Signaling 2010 Jul; 3(131): ra54.

Stockton SD, Gomes I, Liu T, Moraje C, Hipólito L, Jones MR, Ma'ayan A, Morón JA, Li H, Devi LA. Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis. Molecular & cellular proteomics : MCP 2015 Jul;.

Stockert JA, Devi LA. Advancements in therapeutically targeting orphan GPCRs. Frontiers in pharmacology 2015; 6.

Gupta A, Fujita W, Gomes I, Bobeck E, Devi LA. Endothelin-converting enzyme 2 differentially regulates opioid receptor activity. British journal of pharmacology 2015 Jan; 172(2).

Cox BM, Christie MJ, Devi L, Toll L, Traynor JR. Challenges for opioid receptor nomenclature: IUPHAR Review 9. British journal of pharmacology 2015 Jan; 172(2).

Fujita W, Gomes I, Devi LA. Heteromers of μ-δ opioid receptors: new pharmacology and novel therapeutic possibilities. British journal of pharmacology 2015 Jan; 172(2).

Gomes I, Gupta A, Bushlin I, Devi LA. Antibodies to probe endogenous G protein-coupled receptor heteromer expression, regulation, and function. Frontiers in pharmacology 2014; 5.

Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA. Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochemical pharmacology 2014 Dec; 92(3).

Kivell B, Uzelac Z, Sundaramurthy S, Rajamanickam J, Ewald A, Chefer V, Jaligam V, Bolan E, Simonson B, Annamalai B, Mannangatti P, Prisinzano TE, Gomes I, Devi LA, Jayanthi LD, Sitte HH, Ramamoorthy S, Shippenberg TS. Salvinorin A regulates dopamine transporter function via a kappa opioid receptor and ERK1/2-dependent mechanism. Neuropharmacology 2014 Nov; 86.

Fujita W, Gomes I, Devi LA. Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR review 10. British journal of pharmacology 2014 Sep; 171(18).

Toniolo EF, Maique ET, Ferreira WA, Heimann AS, Ferro ES, Ramos-Ortolaza DL, Miller L, Devi LA, Dale CS. Hemopressin, an inverse agonist of cannabinoid receptors, inhibits neuropathic pain in rats. Peptides 2014 Jun; 56.

Gomes I, Gupta A, Bushlin I, Devi LA. Antibodies to probe endogenous G protein-coupled receptor heteromer expression, regulation, and function. Frontiers in pharmacology 2014; 5.

Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA. Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochemical pharmacology 2014 Dec; 92(3).

Kivell B, Uzelac Z, Sundaramurthy S, Rajamanickam J, Ewald A, Chefer V, Jaligam V, Bolan E, Simonson B, Annamalai B, Mannangatti P, Prisinzano TE, Gomes I, Devi LA, Jayanthi LD, Sitte HH, Ramamoorthy S, Shippenberg TS. Salvinorin A regulates dopamine transporter function via a kappa opioid receptor and ERK1/2-dependent mechanism. Neuropharmacology 2014 Nov; 86.

Fujita W, Gomes I, Devi LA. Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR review 10. British journal of pharmacology 2014 Sep; 171(18).

Industry Relationships

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.

Below are financial relationships with industry reported by Dr. Devi during 2014 and/or 2015. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Other Activities: Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership.

  • Furiex Pharmaceuticals, Inc.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.

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Tel: 212-241-6545
Fax: 212-996-7214

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Tel: 212-241-6545
Fax: 212-996-7214

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Tel: 212-241-8345
Fax: 212-996-7214