Gether Lab – University of Copenhagen

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CNS > Research > Section for Molecular and Cellular Neuroscience > Gether Lab

Gether Lab

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.

Key publications last 10 years

  • C. Billesbølle, J. Mortensen, … H.H. Sitte, U. Gether and C.J. Loland: Transition metal ion FRET uncovers K+ regulation of a neurotransmitter:sodium symporter. Nature Communications (2016) 7, 12755.
  • F.H. Hansen, T. Skjørringe, … L.E. Hjermind, L.B. Møller and U. Gether: Missense dopamine transporter mutations associate with adult parkinsonism and ADHD. J Clin Invest (2014) 124, 3107-20
  • B. Holst, K. L. Madsen, A. M. Jansen, … O. Kjærulff and U. Gether: PICK1-Deficiency Impairs Secretory Vesicle Biogenesis and Leads to Growth Retardation and Decreased Glucose Tolerance. PLOS Biology  (2013) 11:e1001542
  • M. Rickhag, F. Herborg Hansen, G. Sørensen, … D. P. D. Woldbye, G Wörtwein and U. Gether: A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopaminę transporter. Nature Communications (2013) 4, 1580
  • A. S. Kristensen, J. Andersen, … C. J. Loland, K. Strømgaard and U. Gether: The SLC6 neurotransmitter transporters: Structure, function, and regulation. Pharmacol Rev (2011) 63, 585-640
  • T. S. Thorsen, K. L. Madsen, … K. Strømgaard, L. C. Rønn and U. Gether: Identification of a small molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD. Proc Natl Acad Sci U S A  (2010) 107, 413-418
  • T. Beuming, J. Kniazeff, M. L. Bergmann, L. Shi, L. Gracia, K. Raniszewska, A. H.Newman, J. A. Javitch, H. Weinstein, U. Gether, and C. J. Loland: The dopamine and cocaine binding site in the dopamine transporter are overlapping. e Neuroscience (2008) 11, 780-789

Overall publication metrics: Number of peer reviewed papers: 157; H-index: 54; i10-index: 127

Ulrik Gether

Center co-director, section and lab leader: Professor Ulrik Gether