Paul Janssen , Ph.D.
The Ohio State University
Department of Physiology & Cell Biology
Department of Internal Medicine,
Division of Cardiovascular Medicine
200 Hamilton Hall
1645 Neil Avenue
Columbus, OH 43210
Phone: (614) 247-7838
Education & Training:
Utrecht University, Netherlands, 1994 B.S.& M.S.
in Medical Biology
Utrecht University, Netherlands, 1997 Ph.D. in Cardiac
Universities of Freiburg and Göttingen, Germany, 2000 Postdoctoral
Johns Hopkins University, Baltimore, 2002 Research Associate
Research in the Janssen lab focuses on various aspects of myocardial relaxation. Cardiac relaxation is no longer thought to be a mere passive process that logically follows contraction, but is a highly regulated process, involving interactions between calcium removal systems and mechanical molecular motors. We study relaxation using a minimalized systems approach, in which we have the advantage of working in a sub-organ level model (multicellular trabeculae) that still encompasses all the electrical, biochemical, and contractile functions of the whole heart, yet is small enough to control in vitro while allowing for assessment of intracellular events, such as calcium transients. More than half of the patients suffering from heart failure (which kills more people than all cancers and aids combined) suffer from relaxation disorders, and part of our work is to gain understanding in the molecular events that change during progression to heart failure. Using multicellular preparations, under near-physiological conditions, we assess contractile parameters and intracellular calcium handling. In addition to the investigation of physiological relaxation, impaired relaxation is studied in several models, including pulmonary artery banded rabbits, and in various transgenic models in collaborative effects, with a focus on models of muscular dystrophy. Several additional research areas of interest in the lab include the role of hydroxyl radical-induced damage to the heart, the role of frequency-dependent activation of the heart, pharmacological intervention in hypertrophic processes, inotropic therapy using glycolysis intermediates, the role of junction proteins in the heart, and the impact of calcium mishandling in arrhythmogenesis.
- Bakkar N, Ladner K, Canan BD, Liyanarachchi S, Bal NC, Pant M, Periasamy M, Li Q, Janssen PML, Guttridge DC. IKKα and Alternative NF-κB Regulate PGC-1β to Promote Oxidative Muscle Metabolism J Cell Biol., 2012;196:497-511.
- Varian KD, Biesiadecki BJ, Ziolo MT, Davis JP, Janssen PML. Staurosporine Inhibits Frequency Dependent Myofilament Desensitization in Intact Rabbit Cardiac Trabeculae. Biochem. Res. Int., 2012;290971.
- Slabaugh JL, Brunello L, Gyorke S, Janssen PML. Contractile parameters and occurrence of alternans of isolated rat myocardium at supra-physiological stimulation frequency. Am J Physiol Heart Circ Physiol., 2012;302:2267-2275.
- Haizlip KM, Bupha-Intr T, Biesiadecki BJ, Janssen PML. Effects of increased preload on the force frequency response and contractile kinetics in early stages of cardiac muscle hypertrophy. Am J Physiol Heart Circ Physiol. 2012;302:H2509-2517.
- Delfín DA, Xu Y, Schill KE, Mays TA, Canan BD, Zang KE, Barnum JA, Janssen PML*, Rafael-Fortney JA*. Sustaining cardiac claudin-5 levels prevents functional hallmarks of cardiomyopathy in a muscular dystrophy mouse model. Mol Ther., 2012;20:1378-1383. *contributed equally.
- Delfín DA, Zang KE, Schill KE, Patel NT, Janssen PML, Rafael-Fortney JA. Cardiomyopathy in the dystrophin/utrophin-deficient mouse model of severe muscular dystrophy is characterized by dysregulation of matrix metalloproteinases. Neuromuscular Disorders. 2012;(in press).
- Grose WE, Clark KR, Griffin D, Malik V, Shontz KM, Montgomery CL, Lewis S, Brown Jr. RH, Janssen PML, Mendell JR and Rodino-Klapac LR. Homologous Recombination Mediates Functional Recovery of Dysferlin Deficiency Following AAV5 Gene Transfer. PLoS ONE 2012;7:e39233, 2012.
- Little SC, Biesiadecki BJ, Kilic A, Higgins RSD, Janssen PML, Davis JP. The rates of Ca2+ dissociation and cross-bridge detachment from ventricular myofibrils as reported by a fluorescent cardiac Troponin C. J Biol Chem. 2012;287:27930-27940.
- Haizlip KM, Hiranandani N, Biesiadecki BJ, Janssen PML. Impact of Hydroxyl Radical-Induced Injury on Calcium Handling and Myofilament sensitivity in Isolated Myocardium. J Appl. Physiol., 2012;113:766-774.
- Elnakish MT, Hassona MDH, Alhaj MA, Moldovan L, Janssen PML, Khan M, Hassanain HH. Rac-induced left ventricular dilation in thyroxin-treated ZmRacD transgenic mice: role of cardiomyocyte apoptosis and myocardial fibrosis. PLoS ONE, 2012;7:e42500.
- Bupha-Intr T, Haizlip KM, Janssen PML. Role of endothelin in the induction of cardiac hypertrophy in vitro. PLoS ONE, 2012;7:e43179.
- Roof SR, Biesiadecki BJ, Davis JP, Janssen PML, Ziolo MT. Effects of increased systolic Ca2+ and β-adrenergic stimulation on Ca2+ transient decline in NOS1 knockout cardiac myocytes. Nitric Oxide, 2012;27:242-247.
- Elnakish MT, Hassanain HH, Janssen PML. Vascular remodeling-associated hypertension leads to left ventricular hypertrophy and contractile dysfunction in profilin-1 transgenic mice. J. Cardiovasc. Pharmacol., 2012;60:544-552.
- Monasky MM, Taglieri DM, Jacobson AK, Haizlip KM, Solaro RJ, Janssen PML. Post-Translational Modifications of Myofilament Proteins Involved in Length-Dependent Prolongation of Relaxation in Rabbit Right Ventricular Myocardium. Arch Biochem Biophys. 2012 (in press).
- Murray JD, Canan BD, Martin CD, Stangland JE, Rastogi N, Rafael-Fortney JA, Janssen PML. The force-temperature relationship in healthy and dystrophic mouse diaphragm; implications for translational study design. Frontiers in striated muscle physiology. 2012;3:422.
- Kalyanasundaram A, Lacombe VA, Belevych A, Brunello L, Janssen PML, Kranias EG, Knollmann BC, Periasamy M, Györke S. Upregulation of sarcoplasmic reticulum calcium uptake leads to heart failure and early mortality in mice deficient in expression of cardiac Calsequestrin. Cardiovasc. Res. 2012 (in press).
- Nixon BR, Liu B, Scellini B, Tesi C, Piroddi N, Ogut O, Solaro RJ, Ziolo MT, Janssen PML, Davis JP, Poggesi C, Biesiadecki BJ. Tropomyosin Ser-283 pseudo-phosphorylation slows myofibril relaxation. Arch Biochem Biophys. 2012 (in press).
- Milani-Nejad N, Xu Y, Davis JP, Campbell KS, Janssen PML. Affect of muscle length on cross-bridge kinetics in intact cardiac trabeculae at body temperature. J Gen Physiol. 2013;141:133-139.
- Aeffner F, Abdulrahman B, Hickman-Davis JM, Janssen PML, Amer A, Bedwell DM, Sorscher EJ, Davis IC. Heterozygosity for the F508del mutation in the cystic fibrosis transmembrane conductance regulator anion channel attenuates influenza severity. J Infect Dis. 2013 (in press).
- Heller KN, Montgomery CL, Janssen PML, Clark KR, Mendell JR, Rodino-Klapac LR. AAV-mediated Overexpression of Human α7 Integrin Leads to Histological and Functional Improvement in Dystrophic Mice. Molecular Ther. 2013 (in press).
- Elnakish MT, Moldovan L, Khan M, Hassanain HH, Janssen PML. Myocardial Rac1 Exhibits Partial Involvement in Thyroxin-Induced Cardiomyocyte Hypertrophy and its Inhibition is Not Sufficient to Improve Cardiac Dysfunction or Contractile Abnormalities in Mouse Papillary Muscles. J. Cardiovasc. Pharmacol., 2013 (in press).