Thomas Jespersen – University of Copenhagen

Equine Cardiac Group > Researchers > Thomas Jespersen

Thomas Jespersen

Associate Professor, Ph.D, D.Med.Sci.

thojes@sund.ku.dk

Research Profile:

In my research group – The Laboratory of Membrane Protein Physiology (MemPro) - we aim at elucidating the physiological function of membrane embedded and associated proteins, through molecular, biochemical, pharmacological, and electrophysiological investigations.

The focus is on revealing novel functional roles of ion channels and receptors localized in cardiac and epithelial tissue as well as in CNS. Our goal is to incorporate in vitro findings into a whole organ context by the use of ex vivo and in vivo animal models.

Within the field of cardiac electrophysiology we primarily focus of the electrical properties of the atria and how changes in these properties can cause atrial fibrillation. Within the laboratory we perform 1) quantitative PCR, Western blot and confocal microscopy of cardiac tissue, 2) patch-clamping on acutely isolated cardiomyocytes and on culture cells transfected with mutated ion channels characterized in human diseases, 3) action potential recordings of tissue strips from rat and human atria, and 4) Langendorff investigations of isolated beating hearts. In addition to these in vitro and ex vivo methods we have a close collaboration with Prof. Rikke Buhl and Acesion Pharma where in vivo investigations are performed on horse and swine hearts.

Publication:

2013

Andersen MN, Krzystanek K, Petersen F, Bomholtz SH, Olesen SP, Abriel H, Jespersen T, Rasmussen HB. A PI3K-SGK1 pathway promotes Kv7.1 surface expression by inhibiting Nedd4-2. J Biol Chem. 2013 Nov 8. [Epub ahead of print]

Liang B, Nissen JD, Laursen M, Wang X, Skibsbye L, Hearing MC, Andersen MN, Rasmussen HB, Wickman K, Grunnet M, Olesen SP, Jespersen T. G-protein-coupled inward rectifier potassium current contributes to ventricular repolarization. Cardiovasc Res. 2013 Nov 12. [Epub ahead of print]

Hedleya PL, Kanters JK, Dembic M, Jespersen T, Skibsbye L, Aidt FH, Eschen O, Graff C, Behr ER, Schlamowitz S, Corfield V, McKenna WJ, Christiansen M. The role of CAV3 in long QT syndrome: clinical and functional assessment of a caveolin-3/Kv11.1 double heterozygote versus caveolin-3 single heterozygote. Circ. Cardiovasc. Genet. 2013;6:452-61.

Wang X, Liang B, Skibsbye L, Olesen SP, Grunnet M, Jespersen T. GIRK channel activation via adenosine or muscarinic receptors has similar effects on rat atrial electrophysiology. J Cardiovasc Pharmacol. 2013 Aug;62:192-8.

Jørgensen ST, Eriksen HN, Dausell J, Jespersen T, Lambert IH, Hoffmann EK. Double Mutation at the Putative Protein Kinase C Phosphorylation Sites Thr Plus Thr(323) in the Mouse LeukotrieneD4 Receptor Eliminates Homologous Desensitization. Cell Physiol Biochem. 2013:366-78.

2012

Olesen MS, Yuan L, Liang B, Holst AG, Nielsen N, Nielsen JB, Hedley PL, Christiansen M, Olesen SP, Haunsø S, Schmitt N, Jespersen T, Svendsen JH. High Prevalence of Long QT Syndrome Associated SCN5A Variants in Patients with Early-Onset Lone Atrial Fibrillation. Circ Cardiovasc Genet. 2012:23:1092-8.

Hostrup A, Christensen GL, Bentzen BH, Liang B, Aplin M, Grunnet M, Hansen JL, Jespersen T. Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury. Cell Physiol Biochem. 2012;30(3):642-52.

Winkel BG, Larsen MK, Berge KE, Leren TP, Nissen PH, Olesen MS, Hollegaard MV, Jespersen T, Yuan L, Nielsen N, Haunsø S, Svendsen JH, Wang Y, Kristensen IB, Jensen HK, Tfelt-Hansen J, Banner J. The Prevalence of Mutations in KCNQ1, KCNH2, and SCN5A in an Unselected National Cohort of Young Sudden Unexplained Death Cases. J Cardiovasc Electrophysiol. 2012.1540-8167.

Krzystanek K, Rasmussen HB, Grunnet M, Staub O, Olesen SP, Abriel H, Jespersen T. De-ubiquitylase USP2 counteracts Nedd4-2-mediated down-regulation of KCNQ1 potassium channel. Heart Rhythm. 2012:440-8.

Nissen JD, Thomsen MB, Bentzen BH, Diness JG, Diness TG, Jespersen T, Grunnet M. Attenuated ventricular β-Adrenergic response and reduced repolarisation reserve in a rabbit model of chronic heart failure. J. Cardiovascular Pharmacology. 2012:142-50

2011

Diness JG, Skibsbye L, Jespersen T, Bartels ED, Sørensen US, Hansen RS, Grunnet M. Effects on atrial fibrillation in aged hypertensive rats by Ca(2+)-activated K(+) channel inhibition. Hypertension. 2011;57:1129-35.

Andersen MN, Krzystanek K, Jespersen T, Olesen SP, Rasmussen HB. AMP-activated protein kinase down-regulates Kv7.1 cell surface expression. Traffic. 2012;13:143-56.

Tfelt-Hansen J, Winkel BG, Grunnet M, Jespersen T. Cardiac channelopathies and sudden infant death syndrome. Cardiology. 2011;119:21-33.

Olesen MS, Jensen NF, Holst AG, Nielsen JB, Tfelt-Hansen J, Jespersen T, Sajadieh A, Haunsø S, Lund JT, Calloe K, Schmitt N, Svendsen JH. A novel nonsense variant in Nav1.5 cofactor MOG1 eliminates its sodium current increasing effect and may increase the risk of arrhythmias. Can J Cardiol. 2011;27:523.e17-23.

Laursen M, Grunnet M, Olesen SP, Jespersen T, Mow T. Keeping the rhythm - Pro-arrhythmic investigations in isolated Göttingen minipig hearts. J Pharmacol Toxicol Methods. 2011;62:134-44.

Jespersen T. Regulation and physiological function of Na(v) 1.5 and KCNQ1 channels. Acta Physiol. 2011;202 Suppl 683:1-26.

Calloe K, Nof E, Jespersen T, DI Diego JM, Chlus N, Olesen SP, Antzelevitch C, Cordeiro JM. Comparison of the effects of a transient outward potassium channel activator on currents recorded from atrial and ventricular cardiomyocytes. J Cardiovasc Electrophysiol. 2011;22:1057-66.

Olesen MS, Jabbari J, Holst AG, Nielsen JB, Steinbrüchel DA, Jespersen T, Haunsø S, Svendsen JH. Screening of KCNN3 in patients with early-onset lone atrial fibrillation. Europace. 2011;13:963-7.

Laursen M, Olesen SP, Grunnet M, Mow T, Jespersen T. Characterization of cardiac repolarization in the Göttingen minipig. J Pharmacol Toxicol Methods. 2011;63:186-95.

2010

Olesen MS, Jespersen T, Nielsen JB, Liang B, Møller DV, Hedley P, Christiansen M, Varró A, Olesen SP, Haunsø S, Schmitt N, Svendsen JH.Mutations in sodium channel beta subunit SCN3B are associated with early onset lone Atrial Fibrillation.Cardiovasc Res. 2010 Nov 4. [Epub ahead of print].

Lundby A, Jespersen T, Schmitt N, Grunnet M, Olesen SP, Cordeiro JM, Calloe K. Effect of the I(to) activator NS5806 on cloned K(V)4 channels depends on the accessory protein KChIP2. Br J Pharmacol. 2010 Aug;160(8):2028-44.

Diness JG, Nissen JD, Jespersen T, Sørensen US, Al-Shahib B, Grunnet M, Hansen RS. Inhibition of small conductance Ca2+-activated K+ channels terminates and protects against atrial fibrillation. Circulation:A&E. 2010;3:380-90.

Yang Y, Yang Y, Liang B, Liu J, Li J, Grunnet M, Olesen SP, Rasmussen HB, Ellinor PT, Gao L, Lin X, Li L, Wang L, Xiao J, Liu Y, Liu Y, Zhang S, Liang D, Peng L, Jespersen T, Chen YH. Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome. Am. J Human Genetics. 2010;86:872-880.

Holst AG, Liang B, Jespersen T, Bundgaard H, Haunso S, Svendsen JH, Tfelt-Hansen J. Sick sinus syndrome, progressive cardiac conduction disease, atrial flutter and ventricular tachycardia caused by a novel SCN5A mutation. Cardiology. 2010;115:311-6.

Tfelt-Hansen J, Winkel BG, Grunnet M, Jespersen T. Inherited cardiac diseases caused by mutations in the Nav1.5 sodium channel. J Cardiovasc Electrophysiol. 2010;21:107-15.

Calloe K, Soltysinska E, Jespersen T, Lundby A, Antzelevitch C, Olesen SP, Cordeiro JM. Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle. J Mol Cell Cardiol. 2010;48:191-200.

2009

Soltysinska E, Olesen SP, Christ T, Wettwer E, Varró A, Grunnet M, Jespersen T. Transmural expression of ion channels and transporters in human non-diseased and end-stage failing heart. Pflugers Arch. 2009;459:11-23.

Holst AG, Calloe K, Jespersen T, Cedergreen P, Winkel BG, Jensen HK, Leren TP, Haunso S, Svendsen JH, Tfelt-Hansen J. A Novel SCN5A Mutation in a Patient with Coexistence of Brugada Syndrome Traits and Ischaemic Heart Disease. Case Report Med. 2009;2009:963645.

Nissen JD, Diness JG, Diness TG, Hansen RS, Grunnet M, Jespersen T. Pharmacologically induced long QT type 2 can be rescued by activation of IKs with benzodiazepine R-L3 in isolated guinea pig cardiomyocytes. J Cardiovasc Pharmacol. 2009;54:169-77.

Tfelt-Hansen J, Jespersen T, Hofman-Bang J, Rasmussen HB, Cedergreen P, Skovby F, Abriel H, Svendsen JH, Olesen SP, Christiansen M, Haunso S. Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A. Can J Cardiol. 2009;25:156-60.

Diness JG, Hansen RS, Nissen JD, Jespersen T, Grunnet M. Antiarrhythmic effect of IKr activation in a cellular model of LQT3. Heart Rhythm. 2009:100-6.

2008

Bentzen BH, Osadchii O, Jespersen T, Hansen RS, Olesen SP, Grunnet M. Activation of big conductance Ca(2+)-activated K (+) channels (BK) protects the heart against ischemia-reperfusion injury. Pflugers Arch. 2008;457:979-88.

Larsen AP, Olesen SP, Grunnet M, Jespersen T. Characterization of hERG1a and hERG1b potassium channels-a possible role for hERG1b in the I(Kr) current. Pflugers Arch. 2008;456:1137-48.

Jespersen T, Petitprez S, Pruvot E, Keller DI, Corbaz C, Schläpfer J, Abriel H, Kucera JP. Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome. Cardiovasc Res. 2008;78:494-504.

2007

Jespersen T, Membrez M, Nicolas CS, Pitard B, Staub O, Olesen SP, Baró I, Abriel H. The KCNQ1 potassium channel is down-regulated by ubiquitylating enzymes of the Nedd4/Nedd4-like family. Cardiovasc Res. 2007;74:64-74.

Kranjcec D, Bergovec M, Rougier JS, Raguz M, Pavlovic S, Jespersen T, Castella V, Keller DI, Abriel H. Brugada syndrome unmasked by accidental inhalation of gasoline vapors. Pacing Clin Electrophysiol. 2007;30:1294-8.

2006

Jespersen T, Gavillet B, van Bemmelen MX, Cordonier S, Thomas MA, Staub O, Abriel H. Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1. Biochem Biophys Res Commun. 2006;348:1455-62.

Peitersen T, Hougaard C, Jespersen T, Jorgensen NK, Olesen SP, Grunnet M. Subtype-specific, bi-component inhibition of SK channels by low internal pH. Biochem Biophys Res Commun. 2006;343:943-9.

Jespersen T, Grunnet M, Rasmussen HB, Hay-Schmidt A, Olesen SP, Klærke DA. The corticosteroid hormone induced factor (CHIF): a new modulator of KCNQ1 channels? Biochem Biophys Res Commun. 2006;341:979-88.

2005

Jespersen T, Grunnet M, Olesen SP. The KCNQ1 channel: From gene to physiological function. Review. Physiology 20:408-416, 2005.

Grunnet M, Olesen SP, Klaerke DA, Jespersen T. hKCNE4 inhibits the hKCNQ1 potassium current without affecting the activation kinetics. Biochem Biophys Res Commun. 2005;328(4):1146-53

Rougier J-S, van Bemmelen MX, O’Brien MC, Jespersen T, Gavillet B, Apothéloz F, Cordonier S, Staub O, Rotin D, Abriel H. Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins. Am J Physiol Cell Physiol. 2005;288(3):C692-701.

Jensen HS, Callo K, Jespersen T, Jensen BS, Olesen SP. The KCNQ5 potassium channel from mouse: A broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes. Brain Res Mol Brain Res. 2005;139(1):52-62.

2004

Grunnet M, Jespersen T, Perrier JF. 5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels. J Neurosci Res. 2004;78(6):845-54.

Hofman-Bang J, Jespersen T, Grunnet M, Larsen LA, Andersen PS, Kanters JK, Kjeldsen K, Christiansen M. Does KCNE5 play a role in long QT syndrome? Clin Chim Acta. 2004;345(1-2):49-53.

Grunnet M, Jespersen T, and Perrier J-F. 5-HT1A receptors regulate the firing of spinal motoneurons by inhibiting a small-conductance Ca2+-activated K+ channel. J Neurosci Res. 2004;78:845-54.

Duno M, Colding-Jorgensen E, Grunnet M, Jespersen T, Vissing J, Schwartz M. Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype. Eur J Hum Genet. 2004;12:738-43.

Jespersen T, Rasmussen HB, Dupuis D, Grunnet M, Angelo K, Vogel L, Jørgensen NK, Klaerke DA, Olesen SP. Basolateral localization of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif. J Cell Sci. 2004;117:4517-26.

Duch M, Carrasco ML, Jespersen T, Aagaard L, Pedersen FS. An RNA secondary structure bias for non- -mediated deletions in vivo. Nucleic Acids Res. 2004;32:2039-48.

Duch M, Carrasco ML, Jespersen T, Hansen BD, Pedersen FS. Transgene stability for three replication-competent murine leukemia virus vectors. Gene. 2004 Mar 31;329:61-9.

2003

Grunnet M, Jespersen T, Colding-Jørgensen E, Schwartz M, Klaerke DA, Vissing J, Olesen SP, Dunø M. Characterization of two new dominant ClC-1 channel mutations associated with myotonia. Muscle Nerve. 2003;28(6):722-32.

Grunnet M, Rasmussen HB, Hay-Schmidt A, Rosenstierne M, Klaerke DA, Olesen SP, Jespersen T. KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels. Biophys J. 2003;85:1525-37.

Grunnet M, Jespersen T, MacAulay N, Jørgensen NK, Olesen SP, Klaerke DA. Regulation of cloned KCNQ1 potassium channels by changes in cell volume is dependent on an intact cytoskeleton. J Physiol. 2003;549:419-27.

Bahrami S, Jespersen T, Pedersen, Duch M. Mutational library analysis of selected amino acids in the receptor binding domain of envelope of Akv murine leukemia virus by conditionally replication competent bicistronic vectors. Gene. 2003;315:51-61.

Bondebjerg J, Jespersen T, Grunnet M, Meldal M. Solid-Phase Synthesis and Biological Activity of a Thioether Analogue of Conotoxin G1. ChemBioChem 2003, 4:101-9.

2002

Angelo K, Jespersen T, Grunnet M, Nielsen MS, Klaerke DA, Olesen SP. KCNE5 Induces Time- and Voltage-Dependent Modulation of the KCNQ1 Current. Biophys J. 2002 Oct;83(4):1997-2006.

Jespersen T, Grunnet M, Rasmussen HB, Ljungstrom T, Jorgensen NK, Olesen SP, Klaerke DA. KCNE4 is an inhibitory subunit to the KCNQ1 channel. J Physiol. 2002 Jul 1;542(Pt 1):119-30.

Jespersen T, Grunnet M, Angelo K, Klaerke DA, Olesen SP. Dual-function vector for protein expression in both mammalian cells and Xenopus laevis oocytes. Biotechniques. 2002 Mar;32(3):536-8, 540.

Dupuis DS, Schroder RL, Jespersen T, Christensen JK, Christophersen P, Jensen BS, Olesen SP. Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352. Eur J Pharmacol. 2002 Feb 22;437(3):129-37.

2001

Schroder RL, Jespersen T, Christophersen P, Strobaek D, Jensen BS, Olesen SP. KCNQ4 channel activation by BMS-204352 and retigabine. Neuropharmacology. 2001 Jun;40(7):888-98.

Grunnet M, Jespersen T, Angelo K, Frokjaer-Jensen C, Klaerke DA, Olesen SP, Jensen BS. Pharmacological modulation of SK3 channels. Neuropharmacology. 2001 Jun;40(7):879-87.

Korolkova YV, Kozlov SA, Lipkin AV, Pluzhnikov KA, Hadley JK, Filippov AK, Brown DA, Angelo K, Strobaek D, Jespersen T, Olesen SP, Jensen BS, Grishin EV. An ERG channel inhibitor from the scorpion Buthus eupeus. J Biol Chem. 2001 Mar 30;276(13):9868-76.

1999

Jespersen T. 1999. Ph.D report: “Analysis and exploitation of murine leukemia virus cis- and trans-elements using novel transduction systems”.

Jespersen T, Duch M, Carrasco ML, Warming S, Pedersen FS. Expression of heterologous genes from an IRES translational cassette in replication competent murine leukemia virus vectors. Gene. 1999 Nov 1;239(2):227-35.

Duch M, Tolstrup A, Dalum I, Jespersen T, Mouritsen S, Pedersen FS. Functional testing of a bicistronic retroviral vector for intracellular peptide production. Biotechniques. 1999 Jun;26(6):1032-4, 1036.

1997

Jespersen T, Duch M, Pedersen FS. Efficient non-PCR-mediated overlap extension of PCR fragments by exonuclease "end polishing". Biotechniques. 1997 Jul;23(1):48, 50, 52.