Haley E Melikian PhD
|Institution||University of Massachusetts Medical School|
|Address||University of Massachusetts Medical School|
303 Belmont Street
Worcester MA 01605
|B.S. ||University of Massachusetts |
|Ph.D. ||Emory University |
|Postdoctoral Fellow |
Howard Hughes Medical Institute
Department of Biochemistry
Emory University, Atlanta, GA
|Harvard Medical School |
Department of Neurobiology
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.
Potential Rotation Projects1. 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.
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
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
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