Ulrik Gether

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My lab has long-standing expertise in studying the molecular, cellular and physiological function of monoamine receptors and transporters.

The key goals of the lab include:

i) dissecting mechanisms controlling activity and availability of monoamine transporters and receptors in the synapse;

ii) determining how these mechanisms are affected by disease and how they are modulated by drugs;

iii) investigating how genetic variation in monoamine transporters and receptors contributes to diseases characterized by altered monoamine homeostasis; and

iiii) developing genetic mouse models for these diseases and decipher the underlying disease biology. Currently, our main focus is on dopamine and on diseases characterized by dysfunctional dopamine homeostasis such as parkinsonism, ADHD, and addiction.

We use advanced imaging tools (e.g. super-resolution microscopy and live single molecule imaging) and biochemical approaches to study the molecular organization of the monoaminergic presynapse including the role of synaptic scaffold proteins. We use classical pharmacological tools, biophysical techniques and electrophysiology to investigate the molecular phenotype of disease-associated missense mutations in the monoamine receptors/transporters and we develop knock-in mice expressing selected disease mutations as putative novel model for dopamine pathologies.

We have linked missense mutations in the dopamine transporter (DAT) to early-onset parkinsonism and ADHD and we expect our efforts to provide important new opportunities for correlating discrete changes in dopamine homeostasis to disease characteristics. Parallel work involves use of chemogenetics and optogenetics to dissect cellular mechanisms and monoaminergic circuits responsible for the pharmacological actions of psychostimulants (e.g. cocaine and amphetamine) and ADHD medication.

Our translational strategy should have a strong potential for providing a path towards new therapeutic strategies for monoaminergic diseases.

Primary fields of research

Ulrik Gether has expertise in:

• Dugs of abuse including cocaine and amphetamine and their effect on the brain
• Neurotransmitters at the molecular level with focus on dopamine
• Neurotransmitterr receptors and transport proteines
• Dopamine-related diseases (e.g. parkinsonisme, ADHD)
• Genetic basis for how drugs act differentily in different people