Sammanda Ramamoorthy, Ph.D.
Robert Blackwell Smith Building, Room 758A
410 North Clay Street
Richmond, Virginia 23298-0613
Phone: (804) 828-8407
Fax: (804) 827-0377
Complete List of Published Work in MyBibliography
- University of Madras, India
Molecular, cellular and behavioral pharmacology of transporters linked to psychostimulants and antidepressants
Studies in the Ramamoorthy laboratory are aimed at understanding the contribution of neurotransmitter transporters to 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 in relevance to mental illness, drug abuse, aging and neurodegenerative diseases. The monoamine transporters mediate reuptake of released amines from the synapse and thus the activity of amine transporters is of crucial importance in the regulation of aminergic neurotransmission. Medications utilized in the treatment of depression, ADHD, OCD and other psychiatric disorders exhibit high affinity for amine transporters. Furthermore, 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 major goal of the laboratory is to understand thoroughly the molecular basis of transporter regulation. By combining molecular, immunological and biochemical approaches, continuing studies in the laboratory seek to identify signals, and dissecting 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 will be studied at the level of transcriptomics, interactomics, proteomics and lipidomics.
While probing the regulatory mechanisms of amine transporters with increasingly higher resolution, our current efforts are focused in answering theses questions: (i) Is the scientific knowledge gained in in vitro model systems similar and applicable to native systems? (ii) How to translate this knowledge to complex behaviors at a system level? and (iii) Are the dysfunctions in regulatory modules causative factors in altered behavior and in pathophysiology of brain? Our laboratory approaches these unanswered questions, with multi-faceted disciplines including neuro – molecular – biochemical – behavioral – and systems/integrated pharmacology utilizing animal models of depression, addiction, and aging, as well as using newly generated transgenic SERT-knock-in animal models.
Fulfillment of our research accomplishment derives from the translational research efforts from either “Bedside-to-Bench” or “Bench-to-Bedside” that will be beneficial to treat and cure human diseases. In this regard, as a collaborative study with clinical and pharmacogenetic researchers (Dr. Laura Goetzl at Temple University, and Dr. Lindsay Devane at Medical University of South Carolina), Dr. Ramamoorthy’s laboratory is directed to understand the gestational age differences in human placental drug transport, focusing on therapeutic and psychoactive pharmaceuticals using human placental preparations obtained from various gestational ages.
Thus our goal is to relate studies of molecules from cells to native tissues and intact animals and finally to define the mechanisms of normal and abnormal regulation of these neurotransmitter transporters in normal and pathological neurotransmission. Outcome of these studies will provide macroscopic visions and microscopic details of neurotransmitter transporters in both CNS and PNS in: healthy/normal conditions, mental illness, drug abuse, aging and neurodegenerative diseases. These studies would also open up possibilities for developing new therapeutic strategies to treat brain disorders.
Dr. Ramamoorthy’s laboratory is not only dedicated to help answer questions in neurobiology of monoamine transporters, but also committed to train students, fellows and laboratory personnel with new techniques and scientific principles and questions with the hope to motivate and inspire students, fellows and colleagues.
Annamalai B, Mannangatti P, Arapulisamy O, Shippenberg TS, Jayanthi LD, Ramamoorthy S. (2012) Tyrosine phosphorylation of the human serotonin transporter: a role in the transporter stability and function. Molecular Pharmacology. 81:73-85.
Mannangatti P, Arapulisamy O, Shippenberg TS, Ramamoorthy S, Jayanthi LD. (2011) Cocaine up-regulation of the norepinephrine transporter requires threonine 30 phosphorylation by p38 mitogen-activated protein kinase. Journal of Biological Chemistry. 286:20239-50.
Ramamoorthy S, Shippenberg TS, Jayanthi LD. (2011) Regulation of monoamine transporters: role of transporter phosphorylation. Pharmacology and Therapeutics. 129:220-38.
Annamalai B, Mannangatti P, Arapulisamy O, Ramamoorthy S, Jayanthi, LD. (2010) Involvement of threonine 258 and serine 259 motif in amphetamine-induced norepinephrine transporter endocytosis. Journal of Neurochemistry. 115:23-35.
Ramamoorthy S, Samuvel DJ, Balasubramaniam A, See RE, Jayanthi LD. Altered dopamine transporter function and phosphorylation following chronic cocaine self-administration and extinction in rats. Biochemical and Biophysical Research Communications. 391:1517-21.