Gether Lab
Ulrik Gether’s lab has long-standing expertise in studying the molecular, cellular and physiological function of monoamine receptors and transporters.
The key goals of the Gether Lab include i) dissecting mechanisms controlling activity and availability of the monoamine (dopamine, serotonin and norepinephrine) 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, the main focus of Ulrik Gether’s research 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. Ulrik Gether’s lab has linked missense mutations in the dopamine transporter (DAT) to early-onset parkinsonism and ADHD and it is expected that the efforts will 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.
A.L. Ejdrup, J.K. Dreyer, M.D. Lycas, S.H Jørgensen, T.W. Robbins, J.W. Dalley, F. Herborg and U. Gether: Computational modelling identifies key determinants of subregion-specific dopamine dynamics in the striatum. eLife (2025) https://doi.org/10.7554/eLife.105214.1
M. Apuschkin, H.B. Burm, J.H. Schmidt, L.J. Skov, R.C. Andersen, C.F. Bowin, J. Støier, K.L. Jensen, L.P. Posselt, O. Dmytriyeva, A.T. Sørensen, K.L. Egerod, B. Holst, M. Rickhag, T.W. Schwartz and U. Gether: An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake.
Cell Reports (2024) 43, 114509. doi: 10.1016/j.celrep.2024.114509.
S.H. Jørgensen, A.L. Ejdrup, M.D. Lycas, L.P. Posselt, K.L. Madsen, L. Tian, J.K. Dreyer, F. Herborg, A.T. Sørensen and U. Gether: Behavioral encoding across timescales by region-specific dopamine dynamics. Proc Natl Acad Sci (U.S.A.) (2023) 120(7):e2215230120. doi: 10.1073/pnas.2215230120.
M.D. Lycas, A.L. Ejdrup, A.T. Sørensen, N.O. Haahr, S.H. Jørgensen, D.A. G., J.F. Støier, C. Werner, A.H. Newman, M. Sauer, F. Herborg and U. Gether: Nanoscopic dopamine transporter distribution and conformation are inversely regulated by excitatory drive and D2-autoreceptor activity. Cell Reports (2022) 40(13):111431. doi: 10.1016/j.celrep.2022.111431.
A.L. Ejdrup, M.D. Lycas, N. Lorenzen, A. Konomi, F. Herborg, K.L. Madsen and U. Gether: A density-based enrichment measure for assessing colocalization in single-molecule localization microscopy data. Nature Communications (2022) 13(1):4388. doi: 10.1038/s41467-022-32064-y.
C.K. Herenbrink, J. F. Støier, W.D. Reith, A. Dagra, M.A.C. Gregorek, Y. Li, L. Tian, U. Gether and F. Herborg: Multimodal Detection of Dopamine by Sniffer Cells Expressing Genetically Encoded Fluorescence Sensors. Communications Biology (2022) J5(1):578. doi: 10.1038/s42003-022-03488-5
R.C. Andersen, J.H. Schmidt, J. Rombach, M.D. Lycas, N.R. Christensen, V.K. Lund, D.S. Stapleton, S. S. Pedersen, M.A. Olsen, M. Stoklund, G. Noes-Holt, T.T. Nielsen 1 , M.P. Keller, A.M. Jansen 1 , R. Herlo, M. Pietropaolo, J.B. Simonsen, O. Kjærulff, B. Holst, A.D. Attie, U. Gether and K.L. Madsen: Coding variants identified in diabetic patients alter PICK1 BAR domain function in insulin granule biogenesis. J Clin Invest (2022) e144904. doi: 10.1172/JCI144904.
F. Herborg, K.L. Jensen, S. Tolstoy, N.V. Arends, L.P. Posselt, A. Shekar, J. Aguilar, Vi.K. Lund, K. Erreger, M. Rickhag, M.D. Lykas, M.N. Lonsdale, T. Rahbek-Clemmensen, A.T. Sørensen, A.H. Newman, A. Løkkegaard, O. Kjærulff, Werge, Li.B. Møller, H.JG Matthies, A.Galli, L.E. Hjermind, U. Gether: Dominant-negative actions of a dopamine transporter variant identified in patients with parkinsonism and neuropsychiatric disease. JCI Insight (2021) Aug 10;151496. doi: 10.1172/jci.insight.151496
G. Sorensen, M. Rickhag, D. Leo, M.D. Lycas, P. H. Ridderstrom, P. Weikop, F. Herborg, D. Woldbye, G. Wortwein, R.R. Gainetdinov, A. Fink-Jensen and U. Gether: Disrupted PDZ-domain binding motif of the dopamine transporter uniquely alters nanoscale distribution, dopamine homeostasis and reward motivation. J Biol Chem (2021) DOI:https://doi.org/10.1016/j.jbc.2021.101361
N.R. Christensen*, M. De Luca1*, M.B. Lever, M. Richner, A.B. Hansen, G. Noes-Holt, K.L. Jensen, M. Rathje, D.B. Jensen, S. Erlendsson, C.R.O. Bartling, I. Ammendrup-Johnsen, S.E. Pedersen, M. Schönauer, K.B. Nissen, S.R. Midtgaard, K. Teilum, L. Arleth, A.T. Sørensen, A. Bach, K. Strømgaard, C.F. Meehan, C.B. Vægter, U. Gether and K.L. Madsen: A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain. EMBO Mol Med (2020) 12(6):e11248.
K. Gotfryd, T. Boesen, J.S. Mortensen, G. Khelashvili, M. Quick, D.S. Terry, J.W. Missel, M.V. LeVine, P. Gourdon, S.C. Blanchard, J.A. Javitch, H. Weinstein, C.J. Loland, P. Nissen and U. Gether: X-ray structure of LeuT in an inward-facing occluded conformation reveals mechanism of substrate release. Nature Communications (2020) 11(1), 1005.
Personal Data
Name: Ulrik Gether
Position: Professor of Neuropharmacology
Education
1990: Doctor of Medicine, University of Copenhagen (UCPH).
2000: Dr. Med. Sc., UCPH. Thesis published as review in Endocrine Rev. (cited >1000 times)
Appointments and Training
2017-2025: Professor of Neuropharmacology, Head of Department, Dep. of Neuroscience, UCPH
2015-2017 : Professor of Neuropharmacology, Section Head, Department of Neuroscience and Pharmacology, UCPH, Denmark
2001-: Professor of Neuropharmacology, Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, UCPH, Denmark
1996-2001: Ole Rømer Associate Research Professor, Division of Cellular and Molecular Physiology, Department of Medical Physiology, UCPH, Denmark
1993-1996: Howard Hughes Postdoctoral Fellow, Stanford University Medical School, California, U.S.A. (laboratory of Nobel Laureate, Prof. Brian Kobilka)
1991-1993: Research Fellow, Lab. of Mol. Endocrinology, Rigshospitalet, Copenhagen, Denmark
1990: Internship at Department of Medicine, Hvidovre Hospital, Copenhagen, Denmark
1985-1990: Student in Dr. Thue W. Schwartz's laboratory, Laboratory of Molecular Endocrinology, Rigshospitalet, Copenhagen, Denmark
Selected Awards and Honors
1993: Fulbright Senior Scholarship
1998: Anna Bochardt’s Memorial Award
1998: Scientific Honorary Medal, Danish Society for Theoretical and Applied Therapy
2002: Elected Member of the Royal Danish Academy of Sciences and Letters
2012: Recipient of ’Kirsten og Freddy Johansens Lægevidenskabelige Forskerpris 2012’
2015: Japan Society for the Promotion of Science - Invitation Fellowship (invited 15 days trip with visit to six universities and research institutes)
2017: Recipient of the Order of the Dannebrog from her Majesty the Queen of Denmark
2018: Recipient of ”HN Prisen 2018” (Familien Hede Nielsens Fond).
Selected Positions of Trust and Editorial Work
1996-: Ad hoc reviewer of manuscripts for Science, Nature, Nature Neuroscience, Nature Structural and Molecular Biology, Nature Chemical Biology, Nature Communication, Proceedings of the National Academy of Sciences U.S.A. J. Neuroscience etc.
1999-: Numerous evaluation committees (PhDs, Drs. of Medical Sciences, Professorships) at Univ. of Copenhagen, Aarhus Univ., Karolinska, Oslo Univ., Linköping Univ.)
2000-2006: Board member, Danish Society for Pharmacology and Toxicology
2003-: Executive Committee Member, ‘Basic and Clinical Pharmacology and Toxicology’
2006-: Editorial Board Member, ‘Molecular Pharmacology’
2006-2010: Elected as Vice chair and Chair of the Gordon Research Conference on ‘Membrane Transport Proteins in 2008 and 2010, respectively
2008: Chairman of AERES Evaluation Committee responsible for review of and site-visit at CNRS/INSERM laboratory at Universite Pierre et Marie Curie, Paris
2008-2011: Associate Editor ‘Pharmacology and Therapeutics’
2012-: Editorial Board, ‘Journal of Biological Chemistry’
2015-2016: Member of Program Committee for FENS (Federation of European Neuroscience Societies) Forum 2016, July 2016, Copenhagen
2013-2018: Independent Research Fund Denmark | Medical Sciences (Danmarks Frie Forskningsfond, Rådet for Sundhed og Sygdom). Vice Chair: 2015-17, Chair: 2017-18
2022-: Chair of Governing Board, Neuroscience Academy Denmark (neuroscience PhD program supported with DKK 187 M from the Lundbeck Foundation)
2023-: European Research Council Starting Grant Panel 2023 – LS5 Neuroscience
Selected Other Scientific and Academic Activities
1993-: Invited speaker at ~85 international scientific meetings. Recent examples include:
- 3rd Biannual International Transmembrane Transporter Society Symposium, Oct 29–Nov 1, 2024, Bethesda, Maryland
- Winter Conf. on Brain Research, Jan 27-Feb 1, 2024, Breckenridge, Colorado
- 20th International Microscopy Congress Sept 10-15, 2023, Busan, Korea.
- Winter Conference on Brain Research, Jan 28-Feb 2, 2023, Snowbird, Utah
- Gordon Research Conference on Membrane Transport Proteins, Barcelona, June 12-17, 2022
- Dopamine 2022, May 23-27, Montreal, Canada
- Neuroscience Day 2022, May 5, Lund’s University (plenary lecture)
- Winter Conference on Brain Research, Jan 28-Feb 2, 2019, Snowmass, Colorado
- 3rd Central European Biomedical Congress (CEBC), Krakow, Poland, September 15-18, 2018 (plenary lecture)
- Inaugural Conference of the International Transmembrane Transporter Society, Vienna, September 18-21, 2018
- Gordon Research Conference on Membrane Transport Proteins, Grand Summit Hotel at Sunday River, USA, June 10-15, 2018 (invited discussion leader)
- ASPET 18th Annual Meeting, Nancy Zahniser Memorial Symposium, San Diego, April 21-25, 2018
- 10th SFB35 Symposium on Transporters, Vienna, September 5-8, 2017
- ISN Brain in Flux Satellite Meeting, Maintenon, France, August 25-28, 2017
- BioMedical Transporters, Lausanne, Switzerland, August 6-10, 2017
- Dopamine 2016, Vienna, Austria, September 5-8, 2016
- Gordon Research Seminar and Conference on Membrane Transport Proteins, Il Ciocco, Italy, June 11-17, 2016 (key note speaker and invited speaker)
- Japanese Alcohol, Nicotine and Drug Addiction Conference 2015, Kobe, Japan, October 11-13 (plenary lecture)
- American College of Neuropsychopharmacology, Hollywood, Florida, Dec 6-10, 2015
- ISN Brain in Flux Satellite Meeting, Cairns, Australia, August 20-23, 2015
- Nordic Neuroscience 2015, Trondheim, Norway, June 10-12, 2015
1992-: >60 guest lectures at universities and pharmaceutical companies
1999-2016: Partner in program project funded by the National Institute of Drugs Abuse under the NIH, U.S.A. (collaborators at Columbia, Vanderbilt and Cornell Universities)
2002-: Ad hoc reviewer of grants for National Science Foundation, U.S.A., Austrian Science Foundation, NIH and Human Frontiers Science Program
2004: Co-organizer of Benzon Symposium No. 51 entitled: ‘Neurotransmitter transporters: Basal function and drug targets’
2013: Co-organizer of Benzon Symposium No. 61 entitled: ‘Membrane proteins: structure, function and dynamics’, August 19-22 2013
2018: Co-organizer of “GPCR Pharmacology: The Next Generation”, Oct 31-Nov 2, The Royal Danish Academy of Sciences and Letters Copenhagen
2021: Co-founder of Zyneyro (spin-out company focusing on neuropathic pain treatment)
Leadership, Research Administration and Larger Grants
1996-: In charge of lab now counting 20 people (6 post docs, 6 PhD students, 1 RA, 1 staff scientist, 1 tech and 5 master’s students)
2004-2009: Director of Center for Pharmacogenomics’ DKK 25 M from Danish Research Councils
2008-2013: PI, UCPH Program of Excellence (‘Stjerneprogram’) on ‘Biomolecular Scaffolding of Neurotransmitter Receptors and Transporters’ (DKK 25 M)
2008-2013: Co-PI (one of four) on UNIK Center of Excellence grant entitled ‘Synthetic Biology’ and awarded DKK 120 M from 2009-2014 (Director Prof. B. Lindberg Møller).
2010-2015: Director of ‘Lundbeck Foundation Center for Biomembranes in Nanomedicine’ awarded DKK 34 M from 2010-2015.
2013-2017: PI, UCPH KU2016 Program of Excellence ‘Attention to Dopamine…’, - DKK 19 M
2017-2020: PI for "Larger biomedical Project", Lundbeck Foundation, DKK 10 M
2019-2022: PI for thematic grant “What causes Brain Disease", Lundbeck Foundation, DKK 10 M
2022-2027: Recipient of a Lundbeck Foundation Professorship (DKK 40 M)
Selected Teaching and Supervision
1996-: Since 1996 main supervisor for 30 post docs, 32 PhD student and 37 MS students.
1996-: Pregraduate teaching in physiology and pharmacology (medical/human biology/dentistry students), including >1500 hours of lectures/class teaching plus diverse course leaderships.
Publications
207 peer-reviewed publications in total. Several contributions to high impact journals (2 Nature, 1 Nature Neurosci, 7 Nature Comm, 1 Neuron, 1 Nature Chem Biol, 1 Nature Meth, 2 J Clin Invest, 1 Science Advances, 4 PNAS, 1 PloS Biology, 1 Mol Psych, 1 EMBO Mol Med, 1 JCI Insight, 3 Elife, 5 Cell Rep, 2 Pharmacol Rev, 42 J Biol Chem). 23 papers as conference proceedings/comments/book chapters. Co-inventor on four patents/patent applications. Web of Science: H-index: 61, citations ~14,390; Google Scholar: H-index =74, citations ~22,330 (Orcid ID 0000-0002-0020-3807).
Molecular and cellular biology: Mutagenesis, PCR, protein expression in mammalian cells, primary neuronal cultures (e.g. striatal, dopaminergic)
Pharmacology: Uptake assays, radioligand binding assays, binding assays using fluorescent ligands, cellular assays based on genetically encoded sensors for ligands or second messengers
Biochemistry: Protein expression/purification, western, Co-IP, fluorescent labeling, biotinylation assays, proteomics
Imaging: Confocal fluorescence microscopy (including live fluorescence imaging), immunohistochemistry, super-resolution microscopy (SIM/PALM/STORM)
Viral expression technique in vitro and in vivo for chemogenetics, optogenetics, expression of genetically encoded sensors and other genetic manipulations
Fiber photometry used together with genetically encoded sensors (e.g. dopamine, serotonin, norepinephrine, calcium, PKA)
Genetic mouse models (knock-out mice, knock-in mice, conditional knock-outs)
Mouse behavior: Broad range of models including various pavlovian and operant tasks (e.g. rodent continuous performance test)
Lab members
| Name | Title | Job responsibilities | |
|---|---|---|---|
| Search in Name | Search in Title | Search in Job responsibilities | |
| Ainoa Konomi Pilkati | Postdoc | Gether Lab |
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| Amr Abdeen | Postdoc | Gether Lab |
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| Anna Campana | Postdoc | Gether Lab |
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| Carl-Fredrik Ivar Anders Bowin | External Postdoc | Gether Lab |
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| Hayley Beth Burm | Academic Research Staff | Gether Lab |
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| Jade Degrandmaison | Postdoc | Gether Lab |
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| Jamila Probst Schiødte H Lilja | PhD Fellow | Gether Lab |
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| Jan Hendrik Schmidt | Postdoc | Gether lab |
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| Julia Coll Marques | PhD Fellow | Gether Lab |
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| Karl Mattias Rickhag | Associate Professor | Gether Lab |
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| Leonie Pauline Posselt | Postdoc | Gether lab |
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| Lucia Paggi | Research Assistant | Gether Lab |
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| Mathias Peder Kristensen | Master-Student | Gether Lab |
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| Mie Gunni Kolmos | PhD Fellow | Gether Lab |
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| Sam Ovrom | PhD Fellow | Gether Lab |
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| Stephan Dodt | Postdoc | Gether Lab |
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| Ulrik Gether | Professor | Gether lab |
|