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The neurotransmitter norepinephrine (NE) is involved in brain activities of attention, responses to novelty and stress, learning and memory. NE is also the primary neurotransmitter mediating autonomic sympathetic nervous system processes such as heart rate. The duration and intensity of NE signaling is limited by the presynaptically localized norepinephrine transporter (NET). NET clears released NE through active transport into terminals. NET is also a target for tricyclic antidepressants, NET-selective reuptake inhibitors (NSRIs), and psychostimulants, such as cocaine and is an important contributor to dopamine clearance in the cortex region of the brain. The research in the laboratory investigates genetic variation in the human NET (hNET) and the consequences for transporter function and contribution to psychiatric and cardiovascular disease, with an emphasis on understanding interaction with developmental stages and the environment, particularly in stress-related disorders. The research moves between identifying genetic variation in humans, and studies in cell culture and animal models to answer these questions. SNP discovery and genotyping methods are used to identify genetic variation in hNET in human psychiatric (e.g. attention-deficit hyperactivity disorder (ADHD), major depression) and cardiovascular disorders and to link genetic variation to phenotypes shared across disorders. The lab analyzes the functional impact of transporter gene variants on NET protein expression and trafficking, transporter activity, and regulation by signal transduction pathways. Transgenic mouse models allow for in vivo assessment of the effects of NET variants on cognitive and cardiovascular phenotypes.

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    Keywords

    ADHD Antidepressant Depression Neurotransmitter Norepinephrine Transport Transporter