Sammanda Ramamoorthy, Ph.D.
Professor
Department: Department of Pharmacology and Toxicology
Phone: (804) 828-8407
Fax: (804) 827-0377
Email: sammanda.ramamoorthy@vcuhealth.org
Address/Location:
Robert Blackwell Smith Building, Room 758A
410 North Clay Street
Box 980613
Richmond, Virginia 23298
Education
- University of Madras, India
Research interests
The monoamine transporters mediate the reuptake of released amines from the synapse; thus, the activity of amine transporters is crucial in regulating aminergic neurotransmission. Studies in Dr. Ramamoorthy's laboratory are aimed at understanding the contribution of neurotransmitter transporters in the CNS function, and more specifically, directed toward understanding the role of monoamines such as dopamine, serotonin, and norepinephrine transporters (DAT, SERT, and NET) in normal neurotransmission and relevance to mental illness, drug abuse, aging and neurodegenerative diseases. Medications for treating depression, ADHD, OCD, and other psychiatric disorders exhibit high affinity for these amine transporters. Moreover, amine transporters are molecular targets for psychostimulants/addictive drugs, including cocaine, amphetamines, MDMA (ecstasy), and bath salts. Since the cloning of the human serotonin transporter in 1993, the primary goal of the laboratory has been to understand the molecular basis of transporter regulation. By combining molecular, immunological, and biochemical approaches, continuing studies in the laboratory seek to identify receptors and downstream signaling cascades and dissect cis/trans-signaling pathways that participate in the dynamic process of transporter regulatory pathways in more detail. For example, transporter phosphorylation, trafficking, protein-protein interactions, and stability are studied at the level of transcriptomics, interactomics, proteomics, phosphoproteomics, and lipidomics.
While probing the regulatory mechanisms of amine transporters with increasingly higher resolution, our current efforts are focused on answering (i) is the scientific knowledge gained in in-vitro model systems similar and applicable to native systems? (ii) how to translate this knowledge into complex behaviors at the system level? and (iii) are the dysfunctions in regulatory modules causative factors in altered behavior and brain pathophysiology? Our laboratory approaches these unanswered questions in a multi-faceted way involving neurocircuitry at the molecular, biochemical, neurochemical, behavioral, and systems level integrated pharmacology using both sexes of animal models of addiction, depression, memory, cognitive dysfunction, and aging. Wide array of cutting-edge techniques are employed in Dr. Ramamoorthy’s laboratory conjoining with collaborators, including the generation of novel knock-in mouse models using CRISPR/Cas9 technology, a battery of behavioral assays; neuron-projection specific viral mediated minigene expression; DREADD-mediated manipulations of neuronal activity during behavioral assays; biochemistry; neurochemistry; in vivo fiber photometry; microdialysis; brain slice and in-vivo fast-scan cyclic voltammetry; and in vivo high-speed chronoamperometry.
Our continued effort using a multidisciplinary approach will provide new insights into the causal link between monoamine transporter regulations via phosphorylation and neuro signaling basis for behaviors and how compromised transporter phosphorylation can mediate a switch to a maladaptive set of ensembled behaviors related to neuropsychiatric conditions and substance-use-disorder.
Dr. Ramamoorthy’s laboratory is not only dedicated to helping answer questions in the neurobiology of monoamine transporters but also committed to training students, fellows, and laboratory personnel with new techniques and scientific principles and questions with the hope to motivate and inspire students, fellows, and colleagues.
Complete List of Published Work in My PubMed Bibliography: H-index = 48, i10-index = 77
Google scholar:
https://scholar.google.com/citations?hl=en&user=vYr1OqkAAAAJ
News articles:
VCU study identifies potential therapeutic strategy for treating cocaine use disorder (VCU News)
Blocking Opioid Receptors May Restore Healthy Dopamine Balance (Neuroscience News)
Selected publications
Mayer FP, Stewart A, Varman DR, Moritz AE, Foster JD, Owens AW, Areal LB, Gowrishankar R, Velez M, Wickham K, Phelps H, Katamish R, Rabil M, Jayanthi LD, Vaughan RA, Daws LC, Blakely RD, Ramamoorthy S. Kappa opioid receptor antagonism restores phosphorylation, trafficking and behavior induced by a disease-associated dopamine transporter variant. Mol Psychiatry. 2025. Epub 20250529. doi: 10.1038/s41380-025-03055-4. PubMed PMID: 40442453.
Jayanthi LD, Ramamoorthy S. Role of Phosphorylation of Serotonin and Norepinephrine Transporters in Animal Behavior: Relevance to Neuropsychiatric Disorders. Int J Mol Sci. 2025;26(16). Epub 20250809. doi: 10.3390/ijms26167713. PubMed PMID: 40869034; PMCID: PMC12387081.
Durairaj RV, Ramamoorthy S, Jayanthi LD. Threonine-53 Phosphorylation of Dopamine Transporter Dictates kappa-Opioid Receptor-Mediated Locomotor Suppression, Aversion, and Cocaine Reward. J Neurosci. 2025;45(25). Epub 20250618. doi: 10.1523/JNEUROSCI.0171-25.2025. PubMed PMID: 40393807; PMCID: PMC12178280.
Ragu Varman D, Mannangatti P, Subler MA, Windle JJ, Ramamoorthy S, Jayanthi LD. Blunted Amphetamine-induced Reinforcing Behaviors and Transporter Downregulation in Knock-in Mice Carrying Alanine Mutations at Threonine-258 and Serine-259 of Norepinephrine Transporter. J Mol Neurosci. 2022;72(9):1965-76. Epub 2022/07/20. doi: 10.1007/s12031-022-01988-x. PubMed PMID: 35852782.
Ragu Varman D, Subler MA, Windle JJ, Jayanthi LD, Ramamoorthy S. Novelty-induced hyperactivity and suppressed cocaine induced locomotor activation in mice lacking threonine 53 phosphorylation of dopamine transporter. Behav Brain Res. 2021;408:113267. Epub 2021/04/02. doi: 10.1016/j.bbr.2021.113267. PubMed PMID: 33794225; PMCID: PMC8117066.
Ragu Varman D, Jayanthi LD, Ramamoorthy S. Kappa Opioid Receptor Mediated Differential Regulation of Serotonin and Dopamine Transporters in Mood and Substance Use Disorder. Handb Exp Pharmacol. 2021. Epub 2021/06/18. doi: 10.1007/164_2021_499. PubMed PMID: 34136961.
Ragu Varman D, Jayanthi LD, Ramamoorthy S. Glycogen synthase kinase-3ss supports serotonin transporter function and trafficking in a phosphorylation-dependent manner. J Neurochem. 2021;156(4):445-64. Epub 20200907. doi: 10.1111/jnc.15152. PubMed PMID: 32797733; PMCID: PMC7882002.
Mannangatti P, Ragu Varman D, Ramamoorthy S, Jayanthi LD. Neurokinin-1 Antagonism Distinguishes the Role of Norepinephrine Transporter from Dopamine Transporter in Mediating Amphetamine Behaviors. Pharmacology. 2021;106(11-12):597-605. Epub 2021/09/14. doi: 10.1159/000518033. PubMed PMID: 34515205; PMCID: PMC8578286.
Mannangatti P, Ramamoorthy S, Jayanthi LD. Interference of norepinephrine transporter trafficking motif attenuates amphetamine-induced locomotor hyperactivity and conditioned place preference. Neuropharmacology. 2018;128:132-41. Epub 2017/10/08. doi: 10.1016/j.neuropharm.2017.10.005. PubMed PMID: 28986281; PMCID: PMC5714664.
Sundaramurthy S, Annamalai B, Samuvel DJ, Shippenberg TS, Jayanthi LD, Ramamoorthy S. Modulation of serotonin transporter function by kappa-opioid receptor ligands. Neuropharmacology. 2017;113(Pt A):281-92. Epub 2016/11/05. doi: 10.1016/j.neuropharm.2016.10.011. PubMed PMID: 27743931; PMCID: PMC5148672.
Rajamanickam J, Annamalai B, Rahbek-Clemmensen T, Sundaramurthy S, Gether U, Jayanthi LD, Ramamoorthy S. Akt-mediated regulation of antidepressant-sensitive serotonin transporter function, cell-surface expression and phosphorylation. Biochem J. 2015;468(1):177-90. Epub 2015/03/13. doi: 10.1042/BJ20140826. PubMed PMID: 25761794.
Ramamoorthy S, Shippenberg TS, Jayanthi LD. Regulation of monoamine transporters: Role of transporter phosphorylation. Pharmacol Ther. 2011;129(2):220-38. Epub 2010/10/19. doi: 10.1016/j.pharmthera.2010.09.009. PubMed PMID: 20951731; PMCID: PMC3031138.
Mannangatti P, Arapulisamy O, Shippenberg TS, Ramamoorthy S, Jayanthi LD. Cocaine up-regulation of the norepinephrine transporter requires threonine 30 phosphorylation by p38 mitogen-activated protein kinase. J Biol Chem. 2011;286(23):20239-50. Epub 2011/04/19. doi: 10.1074/jbc.M111.226811. PubMed PMID: 21498515; PMCID: PMC3121486.
Ramamoorthy S, Samuvel DJ, Buck ER, Rudnick G, Jayanthi LD. Phosphorylation of threonine residue 276 is required for acute regulation of serotonin transporter by cyclic GMP. J Biol Chem. 2007;282(16):11639-47. PubMed PMID: 17310063.
Ramamoorthy S, Blakely RD. Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants. Science. 1999;285(5428):763-6. Epub 1999/07/31. PubMed PMID: 10427004.
Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD. Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci U S A. 1993;90(6):2542-6. Epub 1993/03/15. doi: 10.1073/pnas.90.6.2542. PubMed PMID: 7681602; PMCID: PMC46124.