Madsen Lab

• Madsen KL and Dreyer JK. ‘High and low dopamine regulates D1 and D2 mediated signaling in striatal neurons’ Journal of Physiology, 2017 Dec 15;595(24):7271-7272
• Morten L. Karlsen^*, Thor S. Thorsen^*, Niklaus Johner, Ina Ammendrup-Johnsen, Simon Erlendsson, Xinsheng Tian, Jens B. Simonsen, Rasmus Høiberg-Nielsen, Nikolaj M. Christensen, George Khelashvili, Werner Streicher, Kaare Teilum, Bente Vestergaard, Harel Weinstein, Ulrik Gether, Lise Arleth^** and Kenneth L. Madsen^** ‘Structure of dimeric and tetrameric complexes of the BAR domain protein PICK1 determined by small-angle X-ray scattering’  Structure 2015 23 (7), 1258-1270
• Rathje M, Fang H, Bachman JL, Anggono V, Gether U, Huganir RL, Madsen KL. AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons. Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14426-31.
• Holst B*, Madsen KL*, Jansen AM, Jin C, Rickhag M, Lund VK, Jensen M, Bhatia V, Sørensen G, Madsen AN, Xue Z, Møller SK, Woldbye D, Qvortrup K, Huganir R, Stamou D, Kjærulff O, Gether U. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. PLoS Biol. 2013;11(4):e1001542. Epub 2013 Apr 23
• Madsen KL, Thorsen TS, Rahbek-Clemmensen T, Eriksen J, Gether U. Protein Interacting with C Kinase 1 (PICK1) Reduces Reinsertion Rates of Interaction Partners Sorted to Rab11-dependent Slow Recycling Pathway. J Biol Chem. 2012 Apr 6;287(15):12293-308.
• Madsen KL, Bhatia VK, Gether U, Stamou D BAR domains, amphipathic helices and membrane-anchored proteins use the same mechanism to sense membrane curvature., FEBS Lett. 2010 May 3;584(9):1848-55. Review.
• Thor S. Thorsen^*, Kenneth L. Madsen ^*, Nelson Rebola, Anders Bach, Irina Moreira, Dan Peters, Tino Dyhring, Thijs Beuming, Nicolai Stuhr-Hansen, Christophe Mulle, Harel Weinstein, Kristian Strømgaard, Lars Christian B. Rønn and Ulrik Gether. Identification of a small molecule inhibitor of the PICK1 PDZ domain that inhibits synaptic plasticity. PNAS. 2010 Jan 5;107(1):413-8.  
• Vikram K Bhatia, Kenneth L Madsen, Pierre-Yves Bolinger, Andreas Kunding, Per Hedegård, Ulrik Gether and Dimitrios Stamou. Amphipathic motifs in BAR domains are essential for membrane curvature sensing EMBO J. 2009 Nov 4;28(21):3303-14.  
• Hatzakis NS, Bhatia VK, Larsen J, Madsen KL, Bolinger PY, Kunding AH, Castillo J, Gether U, Hedegård P, Stamou D. How curved membranes recruit amphipathic helices and protein anchoring motifs. Nat Chem Biol. 2009 Nov;5(11):835-41.
• Madsen KL, Beuming T, Niv MY, Chang CW, Dev KK, Weinstein H, Gether U. Molecular determinants for the complex binding specificity of the PDZ domain in PICK1. J Biol Chem. 2005 May 27;280(21):20539-48.

Personal data

Name: Kenneth Lindegaard Madsen
Born: October 23. 1975, Taastrup, Denmark
Contact: Dept. of Neuroscience, UCPH Faculty of Health and Medical Sciences
E-mail: lnp353@ku.dk
Phone (+45) 23649401

Publications and Scientific Activities

31 peer reviewed papers (Plos Biology, Nat Chem Bio, PNAS, EMBO, JNS, Nature Com, Structure, JBC)
1140 citations (37 citations/paper), H-index 15, H10 21, 1 Patent.

Speaker

National and international conferences:
2017 EMBO Conference, Endocytic trafficking and signaling, Seerock, Poland
2017 Molecular basis for membrane remodelling and organization, Roscoff, France
2016 FENS, Chair and speaker, Copenhagen, DK
2016 Winter Conference on Brain Research (WCBR), Breckenridge, Colorado, USA
2015 Benzon symposium, Copenhagen, DK
2013 Membranes and Membrane Proteins, CBN Conference, Copenhagen, DK
2012 Winter Conference on Brain Research (WCBR), Snowbird, Utah, USA
2009 Co-organizer of ‘Brain and Mind Forum’, Chair of ‘Reward and Addiction’
2005 Society for Neuroscience 35rd Annual Meeting, Washington DC, USA
2003- Attended >20 international conferences including GRC, SFN with Posters

Education

2005-08 (May) PhD, Faculty of Health and Medical Sciences, UCPH
2002-04 M.Sc., Biochemistry, UCPH
1998-2001 Bachelor, Biochemistry, UCPH
1994-97 Bachelor, Geography, UCPH

Appointments and Awards

2013 Associate Professor, Dept. of Neuroscience and Pharmacology, UCPH
2010-13 Post Doc fellowship, personal grant FSS
2008-10 Post Doc, funded by KU, Programme of Excellence
2004-07 PhD scholarship, Fellowship from Faculty of Health and Medical Sciences
2002-04 M.Sc scholarship, Grant from Bioteknologirådet (DKK 50.000)

Grants

2017 NOVO Pre-seed (DKK 500.000)
2016 FSS FP1 (DKK 2,500,000)
2015 Lundbeckfonden PhD fellowship (DKK 1,575,000)
2014 FSS FP1 (DKK 2,500,000) + FSS (DKK 216,000)
2013 Postdoctoral grant from the Lundbeckfonden (DKK 454,000)
2011 Research grant (‘strategimidler’) from the DNP (DKK 150,000)
2009 Postdoctoral fellowship (3 years) from (FSS) (DKK 2,775,600)

Scientific focus areas

Neurobiology and neuropharmacology with special attention given to the dopamine system and glutamate receptor trafficking during synaptic plasticity in health and disease. Protein-lipid and protein-protein interactions and their pharmacology (particularly PDZ domains). Main methods: advanced light microscopy, including live microscopy and fluorescence energy transfer (FRET) and total internal reflection (TIRF) microscopy.
The research group currently constitutes 10 persons.

• Protein trafficking of transmembrane proteins (by flowcytometry, confocal microscopy, TIRF microscopy of pHluorin)
• Neuronal signaling (by live fluorescence imaging of FRET based biosensors for PKA, PKC etc)
• Nano-structures of receptor-Scaffold complexes and membrane structures (by super resolution microscopy and 'supported cell membrane sheets’)
• Protein-protein interactions (in vitro by fluorescence polarization, SPOT, ex vivo/in vivo by Co-IP and Bio-ID)
• Semi-high throughput screening (by fluorescence polarisation)
• Protein-lipid interactions (by flow cytometry and SPOT)

Peer reviewed journal articles

Madsen KL and Dreyer JK. High and low dopamine regulates D1 and D2 mediated signaling in striatal neurons Journal of Physiology, 2017 Dec 15;595(24):7271-7272

Falk-Petersen CB, Søgaard R, Madsen KL, Klein AB, Frølund B, Wellendorph P. Development of a Robust Mammalian Cell-based Assay for Studying Recombinant α4 β1/3 δ GABAA Receptor Subtypes. Basic Clin Pharmacol Toxicol. 2017 Aug;121(2):119-129

Jacobsen SE, Ammendrup-Johnsen I, Jansen AM, Gether U, Madsen KL, Bräuner-Osborne H. The GPRC6A receptor displays constitutive internalization and sorting to the slow recycling pathway. JBC. 2017 Apr 28;292(17):6910-6926.

Madsen KL, Herlo R. Recursive Alterations of the Relationship between Simple Membrane Geometry and Insertion of Amphiphilic Motifs. Membranes. 2017 Feb 8;7(1)

A Vuorenpää, TN Jørgensen, AH Newman, KL Madsen, M Scheinin, Ulrik Gether “Differential Internalization Rates and Postendocytic Sorting of the Norepinephrine and Dopamine Transporters Are Controlled by Structural Elements in the N Termini” JBC 2016 291 (11), 5634-5651

S Erlendsson, L Arleth, KL Madsen “Response to The Challenges of Polydisperse SAXS Data Analysis: Two Different SAXS Studies of PICK1 Produce Different Structural Models” Structure 2015 23 (11), 1969-1970

Erlendsson S, Madsen KL. “Membrane Binding and Modulation of the PDZ Domain of PICK1.” Membranes 2015. Review

Morten L. Karlsen^*, Thor S. Thorsen^*, Niklaus Johner, Ina Ammendrup-Johnsen, Simon Erlendsson, Xinsheng Tian, Jens B. Simonsen, Rasmus Høiberg-Nielsen, Nikolaj M. Christensen, George Khelashvili, Werner Streicher, Kaare Teilum, Bente Vestergaard, Harel Weinstein, Ulrik Gether, Lise Arleth^** and Kenneth L. Madsen^** ‘Structure of dimeric and tetrameric complexes of the BAR domain protein PICK1 determined by small-angle X-ray scattering’ Structure 2015 23 (7), 1258-1270

Pinheiro PS, Jansen AM, de Wit H, Tawfik B, Madsen KL, Verhage M, Gether U, Sørensen JB ‘The BAR Domain Protein PICK1 Controls Vesicle Number and Size in Adrenal Chromaffin Cells’ The Journal of Neuroscience 2014 Aug 6; 34 (32): 10688-10700

Erlendsson S, Rathje M, Heidarsson PO, Poulsen FM, Madsen KL, Teilum K, Gether U ‘PICK1 (protein interacting with C-kinase 1) binding promiscuity relies on unconventional PDZ (PSD-95/Discs-large/ZO-1 homology) binding modes for non-class II PDZ ligands’ JBC 2014 Jul 13: jbc. M114. 548743

Rathje M, Fang H, Bachman JL, Gether U, Huganir RL, Madsen KL Reply to Wilkinson et al.: Concerning the use of pHluorin-tagged GluA2 as a reporter for NMDA-induced AMPA receptor recycling. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):E305

Rathje M, Fang H, Bachman JL, Anggono V, Gether U, Huganir RL, Madsen KL. AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons. Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14426-31.

Rickhag M, Owens WA, Winkler MT, Strandfelt KN, Rathje M, Sørensen G, Andresen B, Madsen KL, Jørgensen TN, Wörtwein G, Woldbye DP, Sitte H, Daws LC, Gether U. Membrane-permeable C-terminal Dopamine Transporter Peptides Attenuate Amphetamine-evoked Dopamine Release. J Biol Chem. 2013 Sep 20;288(38):27534-44.

Nørager NG, Jensen CB, Rathje M, Andersen J, Madsen KL, Kristensen AS, Strømgaard K. Development of potent fluorescent polyamine toxins and application in labeling of ionotropic glutamate receptors in hippocampal neurons. ACS Chem Biol. 2013 Sep 20;8(9):2033-41.

Sogaard R, Borre L, Braunstein TH, Madsen KL, MacAulay N. Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1. J Biol Chem. 2013 Jul 12;288(28):20195-207.

Holst B*, Madsen KL*, Jansen AM, Jin C, Rickhag M, Lund VK, Jensen M, Bhatia V, Sørensen G, Madsen AN, Xue Z, Møller SK, Woldbye D, Qvortrup K, Huganir R, Stamou D, Kjærulff O, Gether U. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. PLoS Biol. 2013;11(4):e1001542. Epub 2013 Apr 23 *Shared authorship

Rickhag M, Hansen FH, Sørensen G, Strandfelt KN, Andresen B, Gotfryd K, Madsen KL, Vestergaard-Klewe I, Ammendrup-Johnsen I, Eriksen J, Newman AH, Füchtbauer EM, Gomeza J, Woldbye DP, Wörtwein G, Gether U. A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter. Nat Commun. 2013;4:1580.

Madsen KL, Thorsen TS, Rahbek-Clemmensen T, Eriksen J, Gether U. Protein Interacting with C Kinase 1 (PICK1) Reduces Reinsertion Rates of Interaction Partners Sorted to Rab11-dependent Slow Recycling Pathway. J Biol Chem. 2012 Apr 6;287(15):12293-308.

Ammendrup-Johnsen I, Thorsen TS, Gether U, Madsen KL. Serine 77 in the PDZ domain of PICK1 is a protein kinase Cα phosphorylation site regulated by lipid membrane binding. Biochemistry. 2012 Jan 17;51(2):586-96.

Thor S. Thorsen, Kenneth L. Madsen, Tino Dyhring, Anders Bach, Dan Peters, Kristian Strømgaard, Lars Christian B. Rønn and Ulrik Gether. A fluorescence polarization based screening assay for identification of small molecule inhibitors of the PICK1 PDZ domain Combinatorial Chemistry and High Throughput Screening. 2011 Aug;14(7):590-600.

Bach A, Stuhr-Hansen N, Thorsen TS, Bork N, Moreira IS, Frydenvang K, Padrah S, Christensen SB, Madsen KL, Weinstein H, Gether U, Strømgaard K. Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1. Org Biomol Chem 2010 Oct 7;8(19):4281-8.

Madsen KL, Bhatia VK, Gether U, Stamou D BAR domains, amphipathic helices and membrane-anchored proteins use the same mechanism to sense membrane curvature., FEBS Lett. 2010 May 3;584(9):1848-55. Review.

Thor S. Thorsen^*, Kenneth L. Madsen ^*, Nelson Rebola, Anders Bach, Irina Moreira, Dan Peters, Tino Dyhring, Thijs Beuming, Nicolai Stuhr-Hansen, Christophe Mulle, Harel Weinstein, Kristian Strømgaard, Lars Christian B. Rønn and Ulrik Gether. Identification of a small molecule inhibitor of the PICK1 PDZ domain that inhibits synaptic plasticity. PNAS. 2010 Jan 5;107(1):413-8. *Shared authorship

Vikram K Bhatia, Kenneth L Madsen, Pierre-Yves Bolinger, Andreas Kunding, Per Hedegård, Ulrik Gether and Dimitrios Stamou. Amphipathic motifs in BAR domains are essential for membrane curvature sensing EMBO J. 2009 Nov 4;28(21):3303-14.

Jansen AM, Nässel DR, Madsen KL, Jung AG, Gether U, Kjaerulff O. PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system. J Comp Neurol. 2009 Nov 20;517(3):313-32.

Hatzakis NS, Bhatia VK, Larsen J, Madsen KL, Bolinger PY, Kunding AH, Castillo J, Gether U, Hedegård P, Stamou D. How curved membranes recruit amphipathic helices and protein anchoring motifs. Nat Chem Biol. 2009 Nov;5(11):835-41.

Madsen KL, Eriksen J, Milan-Lobo L, Han DS, Niv MY, Ammendrup-Johnsen I, Henriksen U, Bhatia VK, Stamou D, Sitte HH, McMahon HT, Weinstein H, Gether U. Membrane localization is critical for activation of the PICK1 BAR domain. Traffic. 2008 Aug;9(8):1327-43.

Bassan M, Liu H, Madsen KL, Armsen W, Zhou J, Desilva T, Chen W, Paradise A, Brasch MA, Staudinger J, Gether U, Irwin N, Rosenberg PA. Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1. Eur J Neurosci. 2008 Jan;27(1):66-82.

Sogaard R, Werge TM, Bertelsen C, Lundbye C, Madsen KL, Nielsen CH, Lundbaek JA. GABA(A) receptor function is regulated by lipid bilayer elasticity. Biochemistry. 2006 Oct 31;45(43):13118-29.

Madsen KL, Beuming T, Niv MY, Chang CW, Dev KK, Weinstein H, Gether U. Molecular determinants for the complex binding specificity of the PDZ domain in PICK1. J Biol Chem. 2005 May 27;280(21):20539-48.

Bjerggaard C, Fog JU, Hastrup H, Madsen K, Loland CJ, Javitch JA, Gether U. Surface targeting of the dopamine transporter involves discrete epitopes in the distal C terminus but does not require canonical PDZ domain interactions. J Neurosci. 2004 Aug 4;24(31):7024-36.

Patents

Kenneth Madsen, Thor Seneca Thorsen, Dan Peters, Tino Dyhring, Lars Christian Rønn, Ulrik Gether. PDZ DOMAIN MODULATORS. Danish patent application No. PA 2007 00828 (filed on 8 June 2007) and US provisional application No. 60/942,860 (filed on 8 June 2008) was filed on 3 June 2008
(Application No. PCT/EP2008/056814)