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Genomes and Genes | Dan RodenSummaryAffiliation: Vanderbilt University Country: USA Publications
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Publications
Biophysical properties of 9 KCNQ1 mutations associated with long-QT syndromeTao 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....- An allosteric mechanism for drug block of the human cardiac potassium channel KCNQ1Tao 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.... 
Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia riskMarylyn D Ritchie
Professor of Medicine and Pharmacology, Director, Oates Institute for Experimental Therapeutics, Assistant Vice Chancellor for Personalized Medicine, Vanderbilt University School of Medicine, 1285 Medical Research Bldg IV, Nashville, TN 37232 0575
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...- 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... - Electronic medical records as a tool in clinical pharmacology: opportunities and challengesD M Roden
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Clin Pharmacol Ther 91:1083-86. 2012.... - Blocking Scn10a channels in heart reduces late sodium current and is antiarrhythmicTao 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... - Molecular cloning and analysis of zebrafish voltage-gated sodium channel beta subunit genes: implications for the evolution of electrical signaling in vertebratesSameer 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)... - Genetics of acquired long QT syndromeDan 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.... 
Clinical practice. Long-QT syndromeDan M Roden
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0575, USA
N Engl J Med 358:169-76. 2008- Human genomics and its impact on arrhythmiasDan 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.. - Pharmacogenomics: challenges and opportunitiesDan 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... - The US Food and Drug Administration Cardiorenal Advisory Panel and the drug approval processDan M Roden
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Circulation 111:1697-702. 2005 - Arrhythmia pharmacogenomics: methodological considerationsDan 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... - Proarrhythmia as a pharmacogenomic entity: a critical review and formulation of a unifying hypothesisDan 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.... - Long QT syndrome: reduced repolarization reserve and the genetic linkD 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... - Development of a large-scale de-identified DNA biobank to enable personalized medicineD 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... - Cellular basis of drug-induced torsades de pointesD 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... - Drug-induced prolongation of the QT intervalDan M Roden
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
N Engl J Med 350:1013-22. 2004 - Cardiovascular pharmacogenomicsDan 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 - Antiarrhythmic drugs: past, present and futureDan M Roden
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
J Cardiovasc Electrophysiol 14:1389-96. 2003 - Antiarrhythmic drugs: past, present, and futureDan M Roden
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
Pacing Clin Electrophysiol 26:2340-9. 2003 - Genetic polymorphisms, drugs, and proarrhythmiaDan 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.... - On the relationship among QT interval, atrial fibrillation, and torsade de pointesDan M Roden
Department of Medicine, Pediatrics, and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Europace 9:iv1-3. 2007 - Cardiovascular pharmacogenomicsDan 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... - Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointesPing 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... - Voltage-gated sodium channels are required for heart development in zebrafishSameer 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... - Phosphorylation of the IKs channel complex inhibits drug block: novel mechanism underlying variable antiarrhythmic drug actionsTao Yang
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, RRB532C, Nashville, TN 37232, USA
Circulation 108:132-4. 2003..These data identify a novel mechanism for modulation of drug-channel interactions that may be especially important during beta-adrenergic stimulation... - New mechanism contributing to drug-induced arrhythmia: rescue of a misprocessed LQT3 mutantKai 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... - Robust replication of genotype-phenotype associations across multiple diseases in an electronic medical recordMarylyn 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.... - A structural requirement for processing the cardiac K+ channel KCNQ1Hideaki 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... - Mutations in sodium channel β1- and β2-subunits associated with atrial fibrillationHiroshi 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... - A calcium sensor in the sodium channel modulates cardiac excitabilityHanno L Tan
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville 37232, Tennessee, USA
Nature 415:442-7. 2002.... - Cardiac potassium channel dysfunction in sudden infant death syndromeTroy E Rhodes
Department of Medicine, Vanderbilt University, Nashville, TN, USA
J Mol Cell Cardiol 44:571-81. 2008.... - Polymorphism screening in the cardiac K+ channel gene KCNA5Chantale 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... - Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium currentBenoit 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)... - Genetic variation in the rhythmonome: ethnic variation and haplotype structure in candidate genes for arrhythmiasWilliam 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... - Calmodulin inhibitor W-7 unmasks a novel electrocardiographic parameter that predicts initiation of torsade de pointesT David Gbadebo
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn 37232-6300, USA
Circulation 105:770-4. 2002.... - Calmodulin kinase II and arrhythmias in a mouse model of cardiac hypertrophyYuejin Wu
Department of Internal Medicine, Vanderbilt University, Nashville, Tenn, USA
Circulation 106:1288-93. 2002..Cellular studies point to EADs as a triggering mechanism for arrhythmias but suggest that the increase in arrhythmias after beta-adrenergic stimulation is independent of enhanced EAD frequency... - Unusual effects of a QT-prolonging drug, arsenic trioxide, on cardiac potassium currentsBenoit Drolet
Division of Clinical Pharmacology, 532 Robinson Research Building, Vanderbilt University School of Medicine, Nashville, Tenn 37232, USA
Circulation 109:26-9. 2004..We infer that variability in the extent of QT interval prolongation and onset of ventricular arrhythmias during arsenic therapy represents competing effects to block and activate multiple repolarizing potassium currents... - ACE I/D polymorphism associated with abnormal atrial and atrioventricular conduction in lone atrial fibrillation and structural heart disease: implications for electrical remodelingHiroshi 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... - Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humansHiroshi 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... - Human cardiac potassium channel DNA polymorphism modulates access to drug-binding site and causes drug resistanceBenoit 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... - Images in cardiovascular medicine. Himalayan T waves in the congenital long-QT syndromeDawood Darbar
Vanderbilt University Medical Center, Nashville, Tenn, USA
Circulation 111:e161. 2005 - Rate-independent QT shortening during exercise in healthy subjects: terminal repolarization does not shorten with exercisePrince 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... - Probing the mechanisms underlying modulation of quinidine sensitivity to cardiac I(Ks) block by protein kinase A-mediated I(Ks) phosphorylationTao 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... - Modulation of drug block of the cardiac potassium channel KCNA5 by the drug transporters OCTN1 and MDR1Tao 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.... - An analytical approach to characterize morbidity profile dissimilarity between distinct cohorts using electronic medical recordsJonathan 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... - A genetic framework for improving arrhythmia therapyBjorn 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... - Persistent atrial fibrillation is associated with reduced risk of torsades de pointes in patients with drug-induced long QT syndromeDawood 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)... - PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associationsJoshua 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... - Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humansHiroshi 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... - Close bidirectional relationship between chronic kidney disease and atrial fibrillation: the Niigata preventive medicine studyHiroshi 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... - Prolonged signal-averaged P-wave duration as an intermediate phenotype for familial atrial fibrillationDawood 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... - Cardiac ion channelsDan 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... - Suppression of bidirectional ventricular tachycardia and unmasking of prolonged QT interval with verapamil in Andersen's syndromePrince J Kannankeril
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2572, USA
J Cardiovasc Electrophysiol 15:119. 2004 - In vivo identification of genes that modify ether-a-go-go-related gene activity in Caenorhabditis elegans may also affect human cardiac arrhythmiaChristina 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... - Symptomatic burden as an endpoint to evaluate interventions in patients with atrial fibrillationDawood 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... - Genetic susceptibility to acquired long QT syndrome: pharmacologic challenge in first-degree relativesPrince 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)... - Unmasking of brugada syndrome by lithiumDawood 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... - The genetic basis of variability in drug responsesDan 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... - Pharmacogenetics of antiarrhythmic therapyDawood 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.... - Arrhythmogenic right ventricular cardiomyopathy due to a novel plakophilin 2 mutation: wide spectrum of disease in mutation carriers within a familyPrince 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... - Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardiaBjorn 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.... - A shock in timeRobert Warne Fitch
Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-8828, USA
Clin J Sport Med 17:497-9. 2007 - A memorable experienceKen 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... - Autonomic tone attenuates drug-induced QT prolongationAndrew 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... - Polymorphism modulates symptomatic response to antiarrhythmic drug therapy in patients with lone atrial fibrillationDawood Darbar
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37323 6602, USA
Heart Rhythm 4:743-9. 2007.... - A rate-independent method of assessing QT-RR slope following conversion of atrial fibrillationDawood 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... - The IKr drug response is modulated by KCR1 in transfected cardiac and noncardiac cell linesSabina 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... - Defective human Ether-à-go-go-related gene trafficking linked to an endoplasmic reticulum retention signal in the C terminusSabina 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... - Drug-induced long QT and torsade de pointes: recent advancesPrince 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... - Symptomatic response to antiarrhythmic drug therapy is modulated by a common single nucleotide polymorphism in atrial fibrillationBabar 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)... - Striking In vivo phenotype of a disease-associated human SCN5A mutation producing minimal changes in vitroHiroshi 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... - Informatic and functional approaches to identifying a regulatory region for the cardiac sodium channelThomas 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... - Development of the cardiac conduction system as delineated by minK-lacZRichard 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... - Clinical, genetic, and biophysical characterization of a homozygous HERG mutation causing severe neonatal long QT syndromeWalter 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... - The problem, challenge and opportunity of genetic heterogeneity in monogenic diseases predisposing to sudden deathDan M Roden
J Am Coll Cardiol 40:357-9. 2002 - Bidirectional ventricular tachycardia and channelopathyPreecha 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... - Defining the cellular phenotype of "ankyrin-B syndrome" variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytesPeter 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... - The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndromeNaomasa Makita
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
J Clin Invest 118:2219-29. 2008.... - Repolarization reserve: a moving targetDan M Roden
Circulation 118:981-2. 2008 - Brugada-type ECG pattern and extreme QRS complex widening with propafenone overdoseCan Hasdemir
Department of Cardiology, Ege University School of Medicine, Bornova, Izmir, Turkey
J Cardiovasc Electrophysiol 17:565-6. 2006 - Common sodium channel promoter haplotype in asian subjects underlies variability in cardiac conductionConnie 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... - The molecular genetics of arrhythmiasConnie R Bezzina
Cardiovasc Res 67:343-6. 2005 - Atrial fibrillation in KCNE1-null miceJoel 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... - Drug-induced torsades de pointes and implications for drug developmentRobert 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... - 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 ComDouglas P Zipes
J Am Coll Cardiol 48:e247-346. 2006
Research Grants
- HEPATIC DRUG TRANSPORTERS IN DRUG DISPOSITIONDan 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. ..
- MODULATION OF CARDIAC REPOLARIZATIONDan Roden; Fiscal Year: 2007....
- PHARMACOGENOMICS OF ARRHYTHMIA THERAPYDan 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 ..
- Vanderbilt Genome-Electronic Records ProjectDan Roden; Fiscal Year: 2007....
- Modulation for Cardiac RepolarizationDan Roden; Fiscal Year: 2005..abstract_text> ..
- MODULATION OF CARDIAC REPOLARIZATIONDan 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. ..
- Molecular Pathology of Cardic ArrhythmiasDan Roden; Fiscal Year: 2003..abstract_text> ..
- MODULATION OF CARDIAC REPOLARIZATIONDan M Roden; Fiscal Year: 2010....