Lakshmi A Devi, PhD
- DEAN FOR ACADEMIC DEVELOPMENT AND ENRICHMENT
- PROFESSOR | Pharmacological Sciences
- PROFESSOR | Neuroscience
- PROFESSOR | Psychiatry
Research Topics:Addiction, Enzymology, Hormones, Neural Networks, Neuropeptides, Opioid/Cannabinoid Receptors, Post-Transcriptional Processing, Protein Trafficking & Sorting, Proteomics, Signal Transduction
Dr. Devi is Professor of the Pharmacology and Systems Therapeutics, Psychiatry and Neuroscience departments. She is the Dean for Academic Development and Enrichment 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.
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Multi-Disciplinary Training AreasBiophysics and Systems Pharmacology [BSP], Neuroscience [NEU]
MSc, University of Mysore
PhD, University of Windsor
Postdoctoral Fellowship, Addiction Research Foundation
Postdoctoral Fellowship, Vollum Institute
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.
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.