Postdoctoral Position Available

Haley Melikian, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Psychiatry

Joint Faculty In:
   Biochemistry and Molecular Pharmacology

Other Affiliation(s):
   Brudnick Neuropsychiatric Research Institute
   Interdisciplinary Graduate Program
   Program in Neuroscience

Cocaine and antidepressant-sensitive monoamine transporters

In my laboratory, we study cellular regulation of cocaine- and antidepressant-sensitive neurotransmitter transporters. Once secreted into the synapse, extracellular neurotransmitter concentrations must be constrained in order to control the intensity, duration and distribution of signaling. The primary mechanism for terminating neurotransmission is reuptake into presynaptic terminals mediated by neurotransmitter transporter proteins. Transporters specific for monoamines, such as dopamine and norepinephrine, are potently blocked by the psychostimulant drugs cocaine and amphetamines, as well as by therapeutic agents such as antidepressants. These drugs act by blocking reuptake, resulting in increased extracellular monoamine levels.

Recent studies have demonstrated that endogenous cellular mechanisms can also alter transporter function. We are currently using biochemical and cell biological approaches to examine the contribution of membrane trafficking to transporter regulation. Additionally, we are using chimeric proteins and point mutants to investigate structural transporter domains and post-translational modifications involved in the regulatory process. Finally, we are exploring how protein-protein interactions influence transporter function and regulation.

Selected Publications

Boudanova, E., Navaroli, D.M., and Melikian, H.E. Amphetamine-induced decreases in dopamine transporter surface expression are protein kinase C-independent, Neuropharmacology, 54(3), 605-612, 2008.

Boudanova, E., Navaroli, D.M., Stevens, Z.M. and Melikian, H.E.   Dopamine transporter endocytic determinants:  Carboxy terminal residues required for basal and PKC-stimulated internalization.  Mol Cell Neurosci, 39, 211-217, 2008.

Holton, K.L., Loder, M.K. and Melikian, H.E. Non-classical and distinct endocytic signals dictate constitutive and PKC-regulated neurotransmitter transporter internalization. Nature Neurosci, 8, 881- 888, 2005.

Loder, M.K. and Melikian, H. E. The dopamine transporter constitutively internalizes and recycles in a protein kinase C-regulated manner in stably transfected PC12 cells. J. Biol. Chem, 278, 22168-22174, 2003.

Melikian, H. E. and Buckley, K.M. Membrane trafficking regulates the activity of the human dopamine transporter. J. Neurosci., 19, 7699-7710, 1999.

Melikian, H.E., Rammamorthy, S. and Blakely, R.D. N-Glycosylation is necessary for human norepinephrine transporter ligand recognition and stability, Mol. Pharm. 50, 266-76, 1996.

Qiang, Y., Melikian, H.E., Levey, A.I. and Blakely, R.D. Plasma membrane antidepressant-sensitive serotonin transporters: Structural and anatomical characterization using affinity-purified antibodies, J. Neurosci. 15, 1261-74, 1995.

Melikian, H.E., McDonald, J.K., Gu, H., Rudnick, G., Moore, K.R. and Blakely, R.D. The human norepinephrine transporter: Biosynthetic studies using a site-directed antibody, J. Biol. Chem. 269, 12290-12297, 1994.

Blakely, R.D., Berson, H.E., Fremeau, R.T., Jr., Caron, M.G., Peek, M.M., Prince, H.K., & Bradley, C.C. Molecular cloning, functional expression, and distribution of the rat brain serotonin transporter, Nature 354, 66-70, 1991.

Potential Rotation Projects

1. This project is to determine the intrinsic motif that targets transporters for internalization from the cell surface. Students will generate transporter point mutants lacking candidate internalization signals and subsequently assess transporter function and trafficking. Students will gain experience with molecular biology techniques, mammalian cell culture, pharmacological assays and cellular trafficking studies.



2. This project is to determine how different transporter isoforms differ in their ability to traffic and be regulated. Students will isolate mRNA from cell lines, perform RT-PCR to identify transporter isoform expression and assess how co-expression of transporter isoforms impacts transporter downregulation. Students will gain experience with molecular biology techniques, mammalian cell culture and pharmacological assays.

Academic Background

Office: BNRI
Phone: 508 856-4045
E-mail: Haley.Melikian@umassmed.edu
Keywords: Intracellular Trafficking, Pharmacology, Addiction, Membrane Transport, Neurobiology

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Postdoctoral Position Available Postdoctoral positions (PhD, MD, and/or DVM) are available for outstanding candidates at the new Irving S. and Betty Brudnick Neuropsychiatric Research Institute in the Department of Psychiatry. The Institute provides a translational research environment in which to study: Molecular analyses of cocaine- and antidepressant-sensitive monoamine transporters Interested applicants should mail or fax a curriculum vitae and three letters of reference to the attention of: Haley E. Melikian, PhD Irving S. and Betty Brudnick Neuropsychiatric Research Institute Department of Psychiatry University of Massachusetts Medical School Room 107 303 Belmont Street Worcester, MA 01604 The University of Massachusetts Medical School is an Equal Employment Opportunity/Affirmative Action Institution.