Sign in to edit your profile (add interests, mentoring, photo, etc.)
    Keywords
    Last Name
    Institution

    Haley E Melikian PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentPsychiatry
    AddressUniversity of Massachusetts Medical School
    303 Belmont Street
    Worcester MA 01605
    Phone508-856-4045
        Overview 
        Narrative

        Academic Background

        B.S. University of Massachusetts
        Amherst, MA
        1980-1984
        Ph.D. Emory University
        Atlanta, GA
        1990-1995
        Postdoctoral Fellow
        Howard Hughes Medical Institute
        Department of Biochemistry
        Emory University, Atlanta, GA

        1995-1997
        Harvard Medical School
        Department of Neurobiology
        Boston, MA
        1997-2000

        Cocaine and antidepressant-sensitive monoamine transporters

        Photo: Haley E. Melikian, PhDIn 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.



        Rotation Projects

        Potential Rotation Projects

        1.  Mechanisms Controlling Amphetamine-Stimulated Dopamine Transporter Trafficking:  Amphetamine exposure causes a rapid loss of dopamine transporter from the plasma membrane, compromising synaptic dopamine removal.  However, the endocytic mechanisms responsible for amphetamine-mediated dopamine transporter internalization are not well understood.  This project will use state-of-the-art cellular imaging and molecular approaches to investigate these mechanisms.  Students will receive training in cellular, molecular and biochemical approaches to understanding neuronal membrane protein trafficking and regulation.

        2. Role of Dopamine Transporter Trafficking in Psychostimulant Addiction:  This project is to determine whether membrane trafficking of the dopamine transporter is required for cocaine and amphetamine addiction.  Students will use RNAi technology to knockdown in vivo proteins required for dopamine transporter trafficking, and subsequently perform biochemical and behavioral studies to assess both transporter trafficking and addictive behaviors, respectively.  This project will train students in cellular, molecular, biochemical and behavioral approaches to studying addiction.

        3. Differential structure/function analysis of biogenic amine transporter trafficking and regulation:  Although all biogenic amine transporters downregulate and internalize in response to PKC activation, recent studies demonstrate that the molecular mechanisms mediating these processes are distinct.  This project will identify dopamine transporter target sequences/domains that confer mechanistic specificity for constitutive and regulated trafficking.  Students will gain expertise in cellular and molecular approaches to understanding membrane trafficking mechanisms.


        Post Docs

        Seeking accomplished and motivated neuroscience Ph.D. graduates for postdoctoral fellowship.  This is an exciting opportunity to study neuronal membrane trafficking mechanisms regulating amphetamine- and cocaine-sensitive monoamine transporters using state-of-art techniques in molecular, cellular and chemical biology.  Candidates will have a demonstrated strong publication record from their doctoral research, with excellent verbal and written skills.  Interested candidates should forward a cover letter, curriculum vitae, and a 1-2 page description of their research interests together with the names and addresses of three references via e-mail to: 

         

        Haley E.Melikian, Ph.D.

        Associate Professor of Psychiatry

        BrudnickNeuropsychiatric Research Institute

        UMASS MedicalSchool

        Haley.melikian@umassmed.edu



        Seeking highly motivated neuroscience Ph.D. graduates for postdoctoral fellowship investigating neuronal membrane trafficking mechanisms regulating amphetamine- and cocaine-sensitive monoamine transporters.  The laboratory uses state-of-art techniques in molecular, cellular and chemical biology.  Preference will be given to trainees with expertise in Drosophila genetics seeking to build upon their previous research expertise, and broaden their training scope into mammalian neurobiology. Candidates will have a demonstrated strong publication record from their doctoral research, with excellent verbal and written skills.  Interested candidates should forward a cover letter, curriculum vitae, and a 1-2 page description of their research interests and career goals, together with the names and addresses of three references via e-mail to: 

        Haley E. Melikian,Ph.D.

        AssociateProfessor of Psychiatry

        BrudnickNeuropsychiatric Research Institute

        UMASS MedicalSchool

        Haley.melikian@umassmed.edu

         



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Gabriel LR, Wu S, Melikian HE. Brain Slice Biotinylation: An Ex Vivo Approach to Measure Region-specific Plasma Membrane Protein Trafficking in Adult Neurons. J Vis Exp. 2014; (86).
          View in: PubMed
        2. Gabriel LR, Wu S, Kearney P, Bellvé KD, Standley C, Fogarty KE, Melikian HE. Dopamine transporter endocytic trafficking in striatal dopaminergic neurons: differential dependence on dynamin and the actin cytoskeleton. J Neurosci. 2013 Nov 6; 33(45):17836-46.
          View in: PubMed
        3. Gabriel, L., Lvov, A., Orthodoxou, D., Rittenhouse, A.R., Kobertz, W.R. and Melikian, H.E. The Acid-Sensitive, Anesthetic-Activated Potassium Leak Channel, KCNK3, Is Regulated By 14-3-3ß-Dependent, PKC-Mediated Endocytic Trafficking. Journal of Biological Chemistry. 2012; 39(287):32354–32366.
        4. Navaroli DM, Stevens ZH, Uzelac Z, Gabriel L, King MJ, Lifshitz LM, Sitte HH, Melikian HE. The plasma membrane-associated GTPase Rin interacts with the dopamine transporter and is required for protein kinase C-regulated dopamine transporter trafficking. J Neurosci. 2011 Sep 28; 31(39):13758-70.
          View in: PubMed
        5. Navaroli DM, Melikian HE. Insertion of tetracysteine motifs into dopamine transporter extracellular domains. PLoS One. 2010; 5(2):e9113.
          View in: PubMed
        6. Gabriel L, Stevens Z, Melikian H. Measuring plasma membrane protein endocytic rates by reversible biotinylation. J Vis Exp. 2009; (34).
          View in: PubMed
        7. Boudanova E, Navaroli DM, Stevens Z, Melikian HE. Dopamine transporter endocytic determinants: carboxy terminal residues critical for basal and PKC-stimulated internalization. Mol Cell Neurosci. 2008 Oct; 39(2):211-7.
          View in: PubMed
        8. Boudanova E, Navaroli DM, Melikian HE. Amphetamine-induced decreases in dopamine transporter surface expression are protein kinase C-independent. Neuropharmacology. 2008 Mar; 54(3):605-12.
          View in: PubMed
        9. Holton KL, Loder MK, Melikian HE. Nonclassical, distinct endocytic signals dictate constitutive and PKC-regulated neurotransmitter transporter internalization. Nat Neurosci. 2005 Jul; 8(7):881-8.
          View in: PubMed
        10. Melikian HE. Neurotransmitter transporter trafficking: endocytosis, recycling, and regulation. Pharmacol Ther. 2004 Oct; 104(1):17-27.
          View in: PubMed
        11. Loder MK, Melikian HE. The dopamine transporter constitutively internalizes and recycles in a protein kinase C-regulated manner in stably transfected PC12 cell lines. J Biol Chem. 2003 Jun 13; 278(24):22168-74.
          View in: PubMed
        For assistance with using Profiles, please refer to the online tutorials or contact UMMS Help Desk or call 508-856-8643.
        Haley's Networks
        Click the "See All" links for more information and interactive visualizations!
        Concepts
        _
        Co-Authors
        _
        Similar People
        _
        Same Department
        Physical Neighbors
        _

        This is an official Page/Publication of the University of Massachusetts Worcester Campus
        Office of the Vice Provost for Research, 55 Lake Ave North, Worcester, Massachusetts 01655
        Questions or Comments? Email: publicaffairs@umassmed.edu Phone: 508-856-1572