Dan Roden

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. pmc Biophysical properties of 9 KCNQ1 mutations associated with long-QT syndrome
    Tao Yang
    Department of Medicine and Pharmacology, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, Tenn, USA
    Circ Arrhythm Electrophysiol 2:417-26. 2009
  2. pmc Personalized medicine to treat arrhythmias
    Dan M Roden
    Vanderbilt University School of Medicine, Nashville, USA Electronic address
    Curr Opin Pharmacol 15:61-7. 2014
  3. pmc Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease mechanisms using GWAS data
    Jonathan D Mosley
    Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America
    PLoS ONE 8:e81503. 2013
  4. pmc Genome wide analysis of drug-induced torsades de pointes: lack of common variants with large effect sizes
    Elijah R Behr
    Cardiovascular Sciences and Genetics Research Centers, St George s University of London, London, United Kingdom
    PLoS ONE 8:e78511. 2013
  5. pmc An allosteric mechanism for drug block of the human cardiac potassium channel KCNQ1
    Tao Yang
    John Oates Institute for Experimental Therapeutics, Departments of Medicine, Pharmacology and Center for Structural Biology, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Mol Pharmacol 83:481-9. 2013
  6. pmc Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia risk
    Marylyn D Ritchie
    Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA
    Circulation 127:1377-85. 2013
  7. pmc Cardiovascular pharmacogenomics: the future of cardiovascular therapeutics?
    Dan M Roden
    Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
    Can J Cardiol 29:58-66. 2013
  8. pmc Electronic medical records as a tool in clinical pharmacology: opportunities and challenges
    D M Roden
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Clin Pharmacol Ther 91:1083-86. 2012
  9. pmc Blocking Scn10a channels in heart reduces late sodium current and is antiarrhythmic
    Tao Yang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Circ Res 111:322-32. 2012
  10. pmc Molecular cloning and analysis of zebrafish voltage-gated sodium channel beta subunit genes: implications for the evolution of electrical signaling in vertebrates
    Sameer S Chopra
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    BMC Evol Biol 7:113. 2007

Research Grants

  1. HEPATIC DRUG TRANSPORTERS IN DRUG DISPOSITION
    Dan Roden; Fiscal Year: 2006
  2. MODULATION OF CARDIAC REPOLARIZATION
    Dan Roden; Fiscal Year: 2007
  3. PHARMACOGENOMICS OF ARRHYTHMIA THERAPY
    Dan Roden; Fiscal Year: 2007
  4. Vanderbilt Genome-Electronic Records Project
    Dan Roden; Fiscal Year: 2007
  5. MODULATION OF CARDIAC REPOLARIZATION
    Dan Roden; Fiscal Year: 2009
  6. Modulation for Cardiac Repolarization
    Dan Roden; Fiscal Year: 2005
  7. Modulation for Cardiac Repolarization
    Dan Roden; Fiscal Year: 2004
  8. Modulation for Cardiac Repolarization
    Dan Roden; Fiscal Year: 2003
  9. MODULATION OF CARDIAC REPOLARIZATION
    Dan Roden; Fiscal Year: 1999
  10. MODULATION OF CARDIAC REPOLARIZATION
    Dan Roden; Fiscal Year: 2000

Collaborators

Detail Information

Publications90

  1. pmc Biophysical properties of 9 KCNQ1 mutations associated with long-QT syndrome
    Tao Yang
    Department of Medicine and Pharmacology, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, Tenn, USA
    Circ Arrhythm Electrophysiol 2:417-26. 2009
    ....
  2. pmc Personalized medicine to treat arrhythmias
    Dan M Roden
    Vanderbilt University School of Medicine, Nashville, USA Electronic address
    Curr Opin Pharmacol 15:61-7. 2014
    ..The development of inexpensive whole genome sequencing holds the promise of identifying patients susceptible to arrhythmias in a presymptomatic phase, and thus implementing preventive therapies. ..
  3. pmc Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease mechanisms using GWAS data
    Jonathan D Mosley
    Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America
    PLoS ONE 8:e81503. 2013
    ..We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms. ..
  4. pmc Genome wide analysis of drug-induced torsades de pointes: lack of common variants with large effect sizes
    Elijah R Behr
    Cardiovascular Sciences and Genetics Research Centers, St George s University of London, London, United Kingdom
    PLoS ONE 8:e78511. 2013
    ..This study argues that common genomic variants do not contribute importantly to risk for drug-induced Torsades de Pointes across multiple drugs. ..
  5. pmc An allosteric mechanism for drug block of the human cardiac potassium channel KCNQ1
    Tao Yang
    John Oates Institute for Experimental Therapeutics, Departments of Medicine, Pharmacology and Center for Structural Biology, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Mol Pharmacol 83:481-9. 2013
    ....
  6. pmc Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia risk
    Marylyn D Ritchie
    Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA
    Circulation 127:1377-85. 2013
    ..ECG QRS duration, a measure of cardiac intraventricular conduction, varies ≈2-fold in individuals without cardiac disease. Slow conduction may promote re-entrant arrhythmias...
  7. pmc Cardiovascular pharmacogenomics: the future of cardiovascular therapeutics?
    Dan M Roden
    Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
    Can J Cardiol 29:58-66. 2013
    ..Approaches to incorporating this new knowledge into clinical care, and the barriers to this concept, are addressed...
  8. pmc Electronic medical records as a tool in clinical pharmacology: opportunities and challenges
    D M Roden
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Clin Pharmacol Ther 91:1083-86. 2012
    ....
  9. pmc Blocking Scn10a channels in heart reduces late sodium current and is antiarrhythmic
    Tao Yang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Circ Res 111:322-32. 2012
    ..Although the sodium channel locus SCN10A has been implicated by genome-wide association studies as a modulator of cardiac electrophysiology, the role of its gene product Nav1.8 as a modulator of cardiac ion currents is unknown...
  10. pmc Molecular cloning and analysis of zebrafish voltage-gated sodium channel beta subunit genes: implications for the evolution of electrical signaling in vertebrates
    Sameer S Chopra
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    BMC Evol Biol 7:113. 2007
    ..To gain further insight into the evolution of electrical signaling in vertebrates, we investigated beta subunit genes in the teleost Danio rerio (zebrafish)...
  11. ncbi request reprint The US Food and Drug Administration Cardiorenal Advisory Panel and the drug approval process
    Dan M Roden
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Circulation 111:1697-702. 2005
  12. pmc Cellular basis of drug-induced torsades de pointes
    D M Roden
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Br J Pharmacol 154:1502-7. 2008
    ..This paper reviews the clinical, cellular, molecular and genetic features of the arrhythmia that may provide an answer to this question and proposes future studies in this area...
  13. pmc Development of a large-scale de-identified DNA biobank to enable personalized medicine
    D M Roden
    Office of Personalized Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Clin Pharmacol Ther 84:362-9. 2008
    ..3 and <0.1%, respectively). The rate of sample accrual is 700-900 samples/week. The advantages of this approach are the rate of sample acquisition and the diversity of phenotypes based on EMRs...
  14. ncbi request reprint Proarrhythmia as a pharmacogenomic entity: a critical review and formulation of a unifying hypothesis
    Dan M Roden
    Department of Medicine, and Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, 532 Medical Research Building I, Nashville, TN 37232, United States
    Cardiovasc Res 67:419-25. 2005
    ....
  15. doi request reprint Clinical practice. Long-QT syndrome
    Dan M Roden
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 0575, USA
    N Engl J Med 358:169-76. 2008
  16. pmc On the relationship among QT interval, atrial fibrillation, and torsade de pointes
    Dan M Roden
    Department of Medicine, Pediatrics, and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Europace 9:iv1-3. 2007
  17. pmc Genetics of acquired long QT syndrome
    Dan M Roden
    Department of Medicine, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Invest 115:2025-32. 2005
    ....
  18. ncbi request reprint Human genomics and its impact on arrhythmias
    Dan M Roden
    Department of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Trends Cardiovasc Med 14:112-6. 2004
    ..syndromes (such as atrial fibrillation or sudden arrhythmic death) include a genetic component, raise the prospect that analysis of genomic variability among individuals and populations may in the future be used to manage patients..
  19. ncbi request reprint Long QT syndrome: reduced repolarization reserve and the genetic link
    D M Roden
    Department of Medicine and Pharmacology, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Intern Med 259:59-69. 2006
    ..Assessing variability in susceptibility to acquired LQTS provides a framework for analysis of other complex gene-environment interactions...
  20. ncbi request reprint Pharmacogenomics: challenges and opportunities
    Dan M Roden
    Vanderbilt University, Nashville, Tennessee, USA
    Ann Intern Med 145:749-57. 2006
    ..Overcoming these challenges holds the promise of improving new drug development and ultimately individualizing the selection of appropriate drugs and dosages for individual patients...
  21. ncbi request reprint Drug-induced prolongation of the QT interval
    Dan M Roden
    Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    N Engl J Med 350:1013-22. 2004
  22. pmc Arrhythmia pharmacogenomics: methodological considerations
    Dan M Roden
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 0575, USA
    Curr Pharm Des 15:3734-41. 2009
    ..Identification of loci for arrhythmia susceptibility in turn provide a starting point for both understanding underlying biologic pathways as well as improved selection appropriate therapies...
  23. pmc Cardiovascular pharmacogenomics
    Dan M Roden
    Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 0575, USA
    Circ Res 109:807-20. 2011
    ..A brief view of potential pathways to implementation is presented...
  24. ncbi request reprint Genetic polymorphisms, drugs, and proarrhythmia
    Dan M Roden
    Director, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, 532 Medical Research Building I, Nashville, TN 37232, USA
    J Interv Card Electrophysiol 9:131-5. 2003
    ....
  25. ncbi request reprint Antiarrhythmic drugs: past, present, and future
    Dan M Roden
    Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Pacing Clin Electrophysiol 26:2340-9. 2003
  26. ncbi request reprint Cardiovascular pharmacogenomics
    Dan M Roden
    Division of Clinical Pharmacology, Vanderbilt University School of Medicine, 532 Medical Research Building I, Nashville, Tenn 37232, USA
    Circulation 108:3071-4. 2003
  27. ncbi request reprint Antiarrhythmic drugs: past, present and future
    Dan M Roden
    Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Cardiovasc Electrophysiol 14:1389-96. 2003
  28. ncbi request reprint Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes
    Ping Yang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn 37232, USA
    Circulation 105:1943-8. 2002
    ..We have previously identified functionally important DNA variants in genes encoding K+ channel ancillary subunits in 11% of an aLQTS cohort...
  29. pmc Voltage-gated sodium channels are required for heart development in zebrafish
    Sameer S Chopra
    Department of Pharmacology, Vanderbilt University School of Medicine, 2215B Garland Ave, 1275 MRBIV Light Hall, Nashville, TN 37232 0575, USA
    Circ Res 106:1342-50. 2010
    ..Mice in which Scn5A (the predominant sodium channel gene in heart) has been knocked out die early in development with cardiac malformations by mechanisms which have yet to be determined...
  30. ncbi request reprint New mechanism contributing to drug-induced arrhythmia: rescue of a misprocessed LQT3 mutant
    Kai Liu
    Departments of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Circulation 112:3239-46. 2005
    ..To address this discrepancy, we tested the hypothesis that this mutant channel is not processed normally...
  31. ncbi request reprint Phosphorylation of the IKs channel complex inhibits drug block: novel mechanism underlying variable antiarrhythmic drug actions
    Tao Yang
    Division of Clinical Pharmacology, Vanderbilt University School of Medicine, RRB532C, Nashville, TN 37232, USA
    Circulation 108:132-4. 2003
    ..Because beta-adrenergic stimulation is a frequent trigger of arrhythmias, we hypothesized that PKA stimulation inhibits drug block...
  32. pmc Mutations in sodium channel β1- and β2-subunits associated with atrial fibrillation
    Hiroshi Watanabe
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 0575, USA
    Circ Arrhythm Electrophysiol 2:268-75. 2009
    ..We also have reported that SCN1B is associated with Brugada syndrome and isolated cardiac conduction disease. We tested the hypothesis that mutations in the 4 sodium channel beta-subunit genes SCN1B-SCN4B contribute to AF susceptibility...
  33. ncbi request reprint A structural requirement for processing the cardiac K+ channel KCNQ1
    Hideaki Kanki
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 279:33976-83. 2004
    ..More generally, we have identified a domain whose structural integrity is required for normal surface expression of the KCNQ1 channel...
  34. pmc Robust replication of genotype-phenotype associations across multiple diseases in an electronic medical record
    Marylyn D Ritchie
    Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Am J Hum Genet 86:560-72. 2010
    ....
  35. ncbi request reprint A calcium sensor in the sodium channel modulates cardiac excitability
    Hanno L Tan
    Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville 37232, Tennessee, USA
    Nature 415:442-7. 2002
    ....
  36. ncbi request reprint Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current
    Benoit Drolet
    Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, U S A
    J Cardiovasc Pharmacol 41:934-7. 2003
    ..Because risperidone is metabolized primarily by CYP2D6, these actions likely enhance risk for risperidone-related QT prolongation and proarrhythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs)...
  37. pmc Cardiac potassium channel dysfunction in sudden infant death syndrome
    Troy E Rhodes
    Department of Medicine, Vanderbilt University, Nashville, TN, USA
    J Mol Cell Cardiol 44:571-81. 2008
    ....
  38. ncbi request reprint Polymorphism screening in the cardiac K+ channel gene KCNA5
    Chantale Simard
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University of Medicine, 532 Medical Research Bldg I, Nashville, TN 37232, USA
    Clin Pharmacol Ther 77:138-44. 2005
    ..In this study we screened an additional gene encoding the cardiac potassium channel KCNA5 (underlying I(Kur)) in 3 ethnic groups and evaluated the functional consequences of the variants identified...
  39. pmc ACE I/D polymorphism associated with abnormal atrial and atrioventricular conduction in lone atrial fibrillation and structural heart disease: implications for electrical remodeling
    Hiroshi Watanabe
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Heart Rhythm 6:1327-32. 2009
    ..The D allele is associated with higher ACE activity and thus higher angiotensin II levels. Angiotensin II stimulates cardiac fibrosis and conduction heterogeneity...
  40. pmc Genetic variation in the rhythmonome: ethnic variation and haplotype structure in candidate genes for arrhythmias
    William S Bush
    Center for Human Genetics Research and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA
    Pharmacogenomics 10:1043-53. 2009
    ..Here, we report an evaluation of the variation and haplotype structure in six key components of the rhythmonome...
  41. ncbi request reprint Unusual effects of a QT-prolonging drug, arsenic trioxide, on cardiac potassium currents
    Benoit Drolet
    Division of Clinical Pharmacology, 532 Robinson Research Building, Vanderbilt University School of Medicine, Nashville, Tenn 37232, USA
    Circulation 109:26-9. 2004
    ..In this study, we evaluated the effects of As2O3 on repolarizing cardiac ion currents...
  42. ncbi request reprint Calmodulin inhibitor W-7 unmasks a novel electrocardiographic parameter that predicts initiation of torsade de pointes
    T David Gbadebo
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn 37232 6300, USA
    Circulation 105:770-4. 2002
    ..ECGs were analyzed from a well-characterized animal model of TdP to identify more reliable predictors of this life-threatening ventricular arrhythmia...
  43. ncbi request reprint Calmodulin kinase II and arrhythmias in a mouse model of cardiac hypertrophy
    Yuejin Wu
    Department of Internal Medicine, Vanderbilt University, Nashville, Tenn, USA
    Circulation 106:1288-93. 2002
    ..CaMKII upregulation and prolonged repolarization are general features of cardiomyopathy, but the role of CaMKII in arrhythmias in cardiomyopathy is unknown...
  44. ncbi request reprint Images in cardiovascular medicine. Himalayan T waves in the congenital long-QT syndrome
    Dawood Darbar
    Vanderbilt University Medical Center, Nashville, Tenn, USA
    Circulation 111:e161. 2005
  45. pmc Human cardiac potassium channel DNA polymorphism modulates access to drug-binding site and causes drug resistance
    Benoit Drolet
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Invest 115:2209-13. 2005
    ..Our data support a model in which this structure impairs access of the drug to a pore-binding site...
  46. pmc Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans
    Hiroshi Watanabe
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Nat Med 15:380-3. 2009
    ..Flecainide completely prevented CPVT in two human subjects who had remained highly symptomatic on conventional drug therapy, indicating that this currently available drug is a promising mechanism-based therapy for CPVT...
  47. pmc Rate-independent QT shortening during exercise in healthy subjects: terminal repolarization does not shorten with exercise
    Prince J Kannankeril
    Oates Institute for Experimental Therapeutics, Clinical Research Center, Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee 37232 9119, USA
    J Cardiovasc Electrophysiol 19:1284-8. 2008
    ..We hypothesized that QT hysteresis is evident within stages of exercise and investigated which component of the QT contributes to hysteresis...
  48. ncbi request reprint Symptomatic burden as an endpoint to evaluate interventions in patients with atrial fibrillation
    Dawood Darbar
    Vanderbilt University School of Medicine, Nashville, Tennessee 37323 6602, USA
    Heart Rhythm 2:544-9. 2005
    ..Therefore, we propose an algorithm to quantify symptomatic AF burden as an endpoint in clinical trials...
  49. pmc Probing the mechanisms underlying modulation of quinidine sensitivity to cardiac I(Ks) block by protein kinase A-mediated I(Ks) phosphorylation
    Tao Yang
    Oates Institute for Experimental Therapeutics, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 0575, USA
    Br J Pharmacol 157:952-61. 2009
    ..In this study, we further tested two competing hypotheses: I(Ks) phosphorylation either (i) modulates access of blocking drugs to a binding site; or (ii) destabilizes the drug-channel interaction...
  50. pmc In vivo identification of genes that modify ether-a-go-go-related gene activity in Caenorhabditis elegans may also affect human cardiac arrhythmia
    Christina I Petersen
    Department of Anesthesiology and Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 101:11773-8. 2004
    ..Our studies demonstrate the feasibility of using C. elegans to assay and potentially identify aLQTS candidate genes...
  51. doi request reprint Close bidirectional relationship between chronic kidney disease and atrial fibrillation: the Niigata preventive medicine study
    Hiroshi Watanabe
    Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
    Am Heart J 158:629-36. 2009
    ..Atrial fibrillation (AF) and chronic kidney disease share risk factors and pathophysiologic mechanisms, suggesting that two conditions have close relationships...
  52. ncbi request reprint Suppression of bidirectional ventricular tachycardia and unmasking of prolonged QT interval with verapamil in Andersen's syndrome
    Prince J Kannankeril
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232 2572, USA
    J Cardiovasc Electrophysiol 15:119. 2004
  53. ncbi request reprint Cardiac ion channels
    Dan M Roden
    Departments of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Annu Rev Physiol 64:431-75. 2002
    ..This review discusses these new tools and how their application to the problem of arrhythmias is generating new mechanistic insights to identify patients at risk for this condition and developing improved antiarrhythmic therapies...
  54. pmc PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations
    Joshua C Denny
    Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA
    Bioinformatics 26:1205-10. 2010
    ..The primary outcome of this study was replication of seven previously known SNP-disease associations for these SNPs...
  55. ncbi request reprint The IKr drug response is modulated by KCR1 in transfected cardiac and noncardiac cell lines
    Sabina Kupershmidt
    Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232 6602, USA
    FASEB J 17:2263-5. 2003
    ..We propose that KCR1, when coupled to HERG, may limit the sensitivity of HERG to proarrhythmic drug blockade and may be a rational target for modifying the proarrhythmic effects of otherwise clinically useful compounds...
  56. pmc An analytical approach to characterize morbidity profile dissimilarity between distinct cohorts using electronic medical records
    Jonathan S Schildcrout
    Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN 37232 2156, USA
    J Biomed Inform 43:914-23. 2010
    ..The phenotypes studied include type II diabetes and type II diabetes controls, peripheral arterial disease and peripheral arterial disease controls, normal cardiac conduction as measured by electrocardiography, and senile cataracts...
  57. pmc Modulation of drug block of the cardiac potassium channel KCNA5 by the drug transporters OCTN1 and MDR1
    Tao Yang
    Oates Institute for Experimental Therapeutics, Departments of Pharmacology and Medicine, University Medical Center, Vanderbilt University School of Medicine, 2215 B Garland Avenue, Nashville, TN 37232 0575, USA
    Br J Pharmacol 161:1023-33. 2010
    ....
  58. ncbi request reprint Drug-induced long QT and torsade de pointes: recent advances
    Prince J Kannankeril
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Curr Opin Cardiol 22:39-43. 2007
    ..This review focuses on mechanisms underlying QT prolongation and proarrhythmia, risk factors, including the role of genetic variants, and the unifying framework of reduced repolarization reserve...
  59. ncbi request reprint The genetic basis of variability in drug responses
    Dan M Roden
    Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, 532 Robinson Research Building, Nashville, Tennessee 37232, USA
    Nat Rev Drug Discov 1:37-44. 2002
    ..Here, we discuss the concept that genetic variants might determine much of this variability in drug response, and propose an algorithm to enable further evaluation of the benefits and pitfalls of this enticing possibility...
  60. ncbi request reprint Defective human Ether-à-go-go-related gene trafficking linked to an endoplasmic reticulum retention signal in the C terminus
    Sabina Kupershmidt
    Departments of Pharmacology and Medicine, Vanderbilt University School of Medicine, 561A Preston Research Building, Nashville, TN 37232, USA
    J Biol Chem 277:27442-8. 2002
    ..Further, our data indicate that a key function of the C-terminal 104 amino acids is to mask the RGR ER retention signal, which becomes exposed when mutations truncate the HERG C terminus...
  61. ncbi request reprint Genetic susceptibility to acquired long QT syndrome: pharmacologic challenge in first-degree relatives
    Prince J Kannankeril
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Heart Rhythm 2:134-40. 2005
    ..The purpose of this study was to test for a genetic component to risk for acquired long QT syndrome (LQTS)...
  62. pmc Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans
    Hiroshi Watanabe
    Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    J Clin Invest 118:2260-8. 2008
    ..Sodium current was lower when NaV1.5 was coexpressed with mutant beta1 or beta1B subunits than when it was coexpressed with WT subunits. These findings implicate SCN1B as a disease gene for human arrhythmia susceptibility...
  63. ncbi request reprint Pharmacogenetics of antiarrhythmic therapy
    Dawood Darbar
    Vanderbilt Arrhythmia Service, Vanderbilt University School of Medicine, Room 1285A, MRB IV, Nashville, TN 37323 6602, USA
    Expert Opin Pharmacother 7:1583-90. 2006
    ....
  64. ncbi request reprint Arrhythmogenic right ventricular cardiomyopathy due to a novel plakophilin 2 mutation: wide spectrum of disease in mutation carriers within a family
    Prince J Kannankeril
    Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 9119, USA
    Heart Rhythm 3:939-44. 2006
    ..Mutations in plakophilin-2 (PKP2), a desmosomal protein, have been reported to underlie familial ARVC. We report a novel ARVC PKP2 mutation and present the clinical findings in three female mutation carriers...
  65. pmc Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia
    Bjorn C Knollmann
    Oates Institute for Experimental Therapeutics and Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232 0575, USA
    J Clin Invest 116:2510-20. 2006
    ....
  66. ncbi request reprint A memorable experience
    Ken Monahan
    Division of Cardiovascular Medicine, Vanderbilt University Medical Center, 383 Preston Research Building 2220 Pierce Avenue, Nashville, TN 37232, USA
    Europace 9:1091-2. 2007
    ..We present the case of a patient with ischaemic cardiomyopathy who exhibited evidence of T-wave memory in the setting of multiple episodes of non-sustained ventricular tachycardia that were triggered by an insect bite...
  67. ncbi request reprint A rate-independent method of assessing QT-RR slope following conversion of atrial fibrillation
    Dawood Darbar
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenneessee 37323 6602, USA
    J Cardiovasc Electrophysiol 18:636-41. 2007
    ..In this study, a newly developed method to study heart rate dependence of the QT interval during AF was applied to assess the QT-RR relationships prior to and following cardioversion in patients with AF...
  68. pmc Polymorphism modulates symptomatic response to antiarrhythmic drug therapy in patients with lone atrial fibrillation
    Dawood Darbar
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37323 6602, USA
    Heart Rhythm 4:743-9. 2007
    ....
  69. pmc Unmasking of brugada syndrome by lithium
    Dawood Darbar
    Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 6602, USA
    Circulation 112:1527-31. 2005
    ..We report here 2 patients who developed the Brugada ECG pattern after administration of lithium, a commonly used drug not previously reported to block cardiac sodium channels...
  70. ncbi request reprint Autonomic tone attenuates drug-induced QT prolongation
    Andrew H Smith
    Division of Pediatric Cardiology, Vanderbilt Children s Hospital, Nashville, Tennessee 37232, USA
    J Cardiovasc Electrophysiol 18:960-4. 2007
    ..The QT interval is a predictor of sudden death. Many drugs prolong the QT, primarily through I(Kr) block. Autonomic tone directly affects heart rate and ventricular repolarization, but its effects in the setting of I(Kr) block are unknown...
  71. pmc Prolonged signal-averaged P-wave duration as an intermediate phenotype for familial atrial fibrillation
    Dawood Darbar
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37323 6602, USA
    J Am Coll Cardiol 51:1083-9. 2008
    ..This study sought to perform a genome-wide linkage analysis in a large atrial fibrillation (AF) kindred using AF and abnormally prolonged signal-averaged (SA) P-wave duration as the phenotype...
  72. pmc Persistent atrial fibrillation is associated with reduced risk of torsades de pointes in patients with drug-induced long QT syndrome
    Dawood Darbar
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37323 6602, USA
    J Am Coll Cardiol 51:836-42. 2008
    ..The goal of this study was to identify markers of torsades de pointes (TdP) in patients with drug-associated long QT syndrome (LQTS)...
  73. ncbi request reprint A shock in time
    Robert Warne Fitch
    Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 8828, USA
    Clin J Sport Med 17:497-9. 2007
  74. ncbi request reprint A genetic framework for improving arrhythmia therapy
    Bjorn C Knollmann
    Vanderbilt University School of Medicine, 1285 Medical Research Building IV, Nashville, Tennessee 37232, USA
    Nature 451:929-36. 2008
    ..By analysing mechanisms that increase susceptibility to arrhythmia in individuals with genetic syndromes, it might be possible to improve current therapies and to develop new ways to treat and prevent common arrhythmias...
  75. pmc Symptomatic response to antiarrhythmic drug therapy is modulated by a common single nucleotide polymorphism in atrial fibrillation
    Babar Parvez
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37323 6602, USA
    J Am Coll Cardiol 60:539-45. 2012
    ..This study tested the hypothesis that response to antiarrhythmic drugs (AADs) is modulated by 3 common loci associated with atrial fibrillation (AF)...
  76. pmc Striking In vivo phenotype of a disease-associated human SCN5A mutation producing minimal changes in vitro
    Hiroshi Watanabe
    Department of Medicine, Vanderbilt University School of Medicine, 2215B Garland Ave, 1285 MRBIV Light Hall, Nashville, TN 37232 0575, USA
    Circulation 124:1001-11. 2011
    ..However, when D1275N is studied in heterologous expression systems, most studies show near-normal sodium channel function. Thus, the relationship of the variant to the clinical phenotypes remains uncertain...
  77. pmc Informatic and functional approaches to identifying a regulatory region for the cardiac sodium channel
    Thomas C Atack
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
    Circ Res 109:38-46. 2011
    ..Although multiple lines of evidence suggest that variable expression of the cardiac sodium channel gene SCN5A plays a role in susceptibility to arrhythmia, little is known about its transcriptional regulation...
  78. ncbi request reprint ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Com
    Douglas P Zipes
    J Am Coll Cardiol 48:e247-346. 2006
  79. ncbi request reprint The problem, challenge and opportunity of genetic heterogeneity in monogenic diseases predisposing to sudden death
    Dan M Roden
    J Am Coll Cardiol 40:357-9. 2002
  80. doi request reprint Repolarization reserve: a moving target
    Dan M Roden
    Circulation 118:981-2. 2008
  81. ncbi request reprint Brugada-type ECG pattern and extreme QRS complex widening with propafenone overdose
    Can Hasdemir
    Department of Cardiology, Ege University School of Medicine, Bornova, Izmir, Turkey
    J Cardiovasc Electrophysiol 17:565-6. 2006
  82. ncbi request reprint Clinical, genetic, and biophysical characterization of a homozygous HERG mutation causing severe neonatal long QT syndrome
    Walter H Johnson
    Department of Pediatrics, L M Bargeron Division of Pediatric Cardiology, University of Alabama at Birmingham, USA
    Pediatr Res 53:744-8. 2003
    ..The homozygous mutation results in absence of functional IKr, causing a profound loss of HERG channel function, creating the equivalent of a "HERG knockout" and leading to a severe phenotype...
  83. ncbi request reprint Development of the cardiac conduction system as delineated by minK-lacZ
    Richard P Kondo
    Institute of Molecular Medicine, University of California, San Diego, California, La Jolla 92093, USA
    J Cardiovasc Electrophysiol 14:383-91. 2003
    ..More recently, the spatial expression of minK-lacZ in the adult mouse heart has been shown, for the larger part, to be coincident with the conduction tissues...
  84. ncbi request reprint Common sodium channel promoter haplotype in asian subjects underlies variability in cardiac conduction
    Connie R Bezzina
    Experimental and Molecular Cardiology Group, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Circulation 113:338-44. 2006
    ..In this study, we tested the hypothesis that an SCN5A promoter polymorphism common in Asians modulates variability in cardiac conduction...
  85. ncbi request reprint Atrial fibrillation in KCNE1-null mice
    Joel Temple
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn 37232 6602, USA
    Circ Res 97:62-9. 2005
    ..Thus, KCNE1 deletion in mice unexpectedly leads to increased outward current in atrial myocytes, shortens atrial action potentials, and enhances susceptibility to atrial fibrillation...
  86. ncbi request reprint The molecular genetics of arrhythmias
    Connie R Bezzina
    Cardiovasc Res 67:343-6. 2005
  87. ncbi request reprint Bidirectional ventricular tachycardia and channelopathy
    Preecha Laohakunakorn
    Bumgrad Hospital, Bangkok, Thailand
    Am J Cardiol 92:991-5. 2003
    ..Genes causing long QT syndrome were used as candidate genes in 4 patients with bidirectional ventricular tachycardia. In 2 patients, we identified a common low penetrance HERG allele (R1047L) with an intermediate biophysical phenotype...
  88. ncbi request reprint Defining the cellular phenotype of "ankyrin-B syndrome" variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes
    Peter J Mohler
    Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA
    Circulation 115:432-41. 2007
    ..More importantly, there is no cellular explanation for the range of severity of cardiac phenotypes associated with specific ANK2 variants...
  89. pmc The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome
    Naomasa Makita
    Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    J Clin Invest 118:2219-29. 2008
    ....
  90. pmc Drug-induced torsades de pointes and implications for drug development
    Robert R Fenichel
    Washington, DC, USA
    J Cardiovasc Electrophysiol 15:475-95. 2004
    ..The final section of the text discusses drug-induced torsades within the larger evaluation of drug-related risks and benefits...

Research Grants23

  1. HEPATIC DRUG TRANSPORTERS IN DRUG DISPOSITION
    Dan Roden; Fiscal Year: 2006
    ..Moreover, variability in the extent of rifampin-mediated induction of the drug metabolizing enzyme, CYP3A, among subjects with variant OATP-C alleles, will also be tested. ..
  2. MODULATION OF CARDIAC REPOLARIZATION
    Dan Roden; Fiscal Year: 2007
    ....
  3. PHARMACOGENOMICS OF ARRHYTHMIA THERAPY
    Dan Roden; Fiscal Year: 2007
    ..Participation in the Network will enable the long-term vision of exploiting human genomic information for more rationale drug development and ..
  4. Vanderbilt Genome-Electronic Records Project
    Dan Roden; Fiscal Year: 2007
    ....
  5. MODULATION OF CARDIAC REPOLARIZATION
    Dan Roden; Fiscal Year: 2009
    ....
  6. Modulation for Cardiac Repolarization
    Dan Roden; Fiscal Year: 2005
    ..abstract_text> ..
  7. Modulation for Cardiac Repolarization
    Dan Roden; Fiscal Year: 2004
    ..abstract_text> ..
  8. Modulation for Cardiac Repolarization
    Dan Roden; Fiscal Year: 2003
    ..abstract_text> ..
  9. MODULATION OF CARDIAC REPOLARIZATION
    Dan Roden; Fiscal Year: 1999
    ..New knowledge in the broad area of the molecular basis of arrhythmogenesis is a crucial step to development of improved therapies for cardiac arrhythmias. ..
  10. MODULATION OF CARDIAC REPOLARIZATION
    Dan Roden; Fiscal Year: 2000
    ..New knowledge in the broad area of the molecular basis of arrhythmogenesis is a crucial step to development of improved therapies for cardiac arrhythmias. ..
  11. MODULATION OF CARDIAC REPOLARIZATION
    Dan Roden; Fiscal Year: 2001
    ..New knowledge in the broad area of the molecular basis of arrhythmogenesis is a crucial step to development of improved therapies for cardiac arrhythmias. ..
  12. Modulation for Cardiac Repolarization
    Dan Roden; Fiscal Year: 2002
    ..abstract_text> ..
  13. Molecular Pathology of Cardic Arrhythmias
    Dan Roden; Fiscal Year: 2003
    ..abstract_text> ..
  14. MODULATION OF CARDIAC REPOLARIZATION
    Dan M Roden; Fiscal Year: 2010
    ....