Kenneth Lindegaard Madsen

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My research addresses fundamental aspects of basic pharmacology, molecular pharmacology and neuropharmacology, with certain potential translational parts. The work is divided into three Work Packages each containing a number of specific projects. Work Package 1 is focused on the pharmacology of PSD95/Disc-large/ZO-1 homology (PDZ) mediated proteins-protein interaction and how these domains might represent new attractive pharmacological targets as alternatives to surface receptors. Work Package 2 will seek to explore the controversial idea that trafficking of receptors and transporters, which in many cases is strongly integrated with their pharmacology, is determined not only by protein-protein interactions, but also by yet unappreciated protein-lipid interactions that govern localization of the receptors and transporters to areas of high membrane curvature in the plasma membrane. Work Package 3 is aimed at obtaining fundamental new understanding of dopamine signaling processes in the brain. Evidently, this has broad pharmacotherapeutic perspectives given the key role of dysfunctional dopamine signaling in many brain disease including schizophrenia, bipolar disorder, ADHD, Parkinsons’ Disease and drug abuse.

Primary fields of research

Signalling and Scaffolding Processes

Molecular Aspects of Synaptic Plasticity

Addiction

PDZ domains

BAR domains

Protein Lipid Interactions

 

Selected publications

1. Published

   PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance

   Holst, Birgitte, Madsen, Kenneth Lindegaard, Jansen, A. M., Jin, C., Rickhag, Karl Mattias, Lund, Viktor Karlovich, Jensen, M., Bhatia, V., Sørensen, G., Madsen, A. N., Xue, Z., Møller, S. K., Woldbye, David Paul Drucker, Qvortrup, Klaus, Huganir, R., Stamou, Dimitrios, Kjærulff, Ole & Gether, Ulrik, Apr 2013, In: P L o S Biology (Online). 11, 4, p. 1-25 25 p., e1001542.

   Research output: Contribution to journal › Journal article › peer-review

2. Published

   Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD

   Thorsen, T. S., Madsen, Kenneth Lindegaard, Rebola, N., Rathje, Mette, Anggono, V., Bach, Anders, Moreira, I. S., Stuhr-Hansen, N., Dyhring, T., Peters, D., Beuming, T., Huganir, R., Weinstein, H., Mulle, C., Strømgaard, Kristian, Rønn, L. C. B. & Gether, Ulrik, 2010, In: Proceedings of the National Academy of Science of the United States of America. 107, 1, p. 413-8 5 p.

   Research output: Contribution to journal › Journal article › peer-review

3. Published

   How curved membranes recruit amphipathic helices and protein anchoring motifs

   Hatzakis, Nikos, Bhatia, V. K., Larsen, J., Madsen, Kenneth Lindegaard, Bolinger, P., Kunding, A. H., Castillo Leon, J. J., Gether, Ulrik, Hedegård, Per & Stamou, Dimitrios, 2009, In: Nature Chemical Biology. 5, 11, p. 835-841 6 p.

   Research output: Contribution to journal › Journal article › peer-review

4. Published

   Amphipathic motifs in BAR domains are essential for membrane curvature sensing

   Bhatia, V. K., Madsen, Kenneth Lindegaard, Bolinger, P., Kunding, A., Hedegård, Per, Gether, Ulrik & Stamou, Dimitrios, 2009, In: EMBO Journal. 28, 21, p. 3303-3314 11 p.

   Research output: Contribution to journal › Journal article › peer-review