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Sammanda Ramamoorthy, PhD
Associate Professor Department of Neuroscience,
Medical University of South Carolina, Charleston, SC.
Phone: (843) 792-3689
Fax: (843) 792-4423
Email: rama@musc.edu
Education:
B.S, Botany, Chemistry, Zoology, 1981, Madras University,Tamil Nadu, India; M.S, Biochemistry, 1983, Madras University,Tamil Nadu, India; Ph.D, Biochemistry, Christian Medical College Hospital, Vellore, Madras University, Tamil Nadu, India
Research Area:
Cellular and Molecular Biology of Neurotransmitter Transporters: Functional Regulation and its Relevance to Neurotransmission, Psychiatric Illnesses, Drug Addiction, Aging and Neurodegenerative Diseases.
Research Description:
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 neurodegerative diseases.
The monoamine transporters are responsible for controlling the magnitude and duration of chemical signaling by clearing the released neurotransmitter back into neuronal terminals and are molecular targets for addictive drugs including cocaine, amphetamines and MDMA (ecstasy) as well as important therapeutic antidepressants. Since the cloning of the human serotonin transporter, the major goal of the laboratory, is to understand thoroughly the molecular basis of serotonin transporter regulation.
The major molecular mechanism underlying signal transduction is protein phosphorylation. Our studies provided evidence that phosphorylation/dephosphorylation cascade may regulate the trafficking (moving transporters on and off the cell surface) of SERTs. More intriguing, and a paradigm shifting finding is the ability of 5-HT, antidepressants, amphetamines and cocaine to regulate SERT phosphorylation and cellular SERT distribution by its own intrinsic activity.
For the first time, our discovery provides evidence for the use dependent modulation “Use It or Lose It” concept of neurotransmitter reuptake and identifies novel activities of antidepressants and psychostimulants linked to SERT phosphorylation. By combining molecular biologic, 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 SERT regulatory pathways in more detail.
In a parallel line of studies in the laboratory, we seek to identify the intermediary candidates in phosphorylation/dephosphorylation cascades regulating transporter function and expression. We have identified the physical association of protein phosphatase 2A catalytic subunit with SERT, DAT and NET. In this line of research, our primary focus is to identify other transporter associated proteins and understand the role of these associated proteins in transporter trafficking, expression and function and to explore whether these interactions are altered in mental illness, drug abuse, aging and neurodegerative diseases.
Transport proteins are not only regulated acutely at the protein level but also chronically at the gene level. In the past, we have identified the upregulation of SERT gene expression by agents like cholera toxin, staurosporine and IL-1ß. SERT gene polymorphisms have been implicated the transporter in anxiety, depression, suicide, autism, and substance abuse. Our strategies are to define cis/trans elements required for the regulation of SERT gene transcription in response to external stimuli and to examine whether these elements are altered, and or responsible for altered SERT expression in abnormal neuronal function.
The final goal is to relate studies of molecules from cells to native tissues and intact animals and to define the mechanisms of normal and abnormal regulation of these neurotransmitter transporters in normal and pathological neurotransmission. Out come of these studies will provide macroscopic visions and the microscopic details of neurotransmitter transporters in both CNS and PNS in: healthy/normal conditions, mental illness, drug abuse, aging and neurodegerative diseases..
These studies would also open up possibilities for developing new therapeutic strategies towards mental illness , drug abuse and other neurological diseases.