ALFRED GEORGE

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. ncbi Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks)
    Andrew L Lundquist
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Mol Cell Cardiol 38:277-87. 2005
  2. ncbi Single-channel properties of human NaV1.1 and mechanism of channel dysfunction in SCN1A-associated epilepsy
    Carlos G Vanoye
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA
    J Gen Physiol 127:1-14. 2006
  3. ncbi Calmodulin mutations associated with recurrent cardiac arrest in infants
    Lia Crotti
    Section of Cardiology, Department of Molecular Medicine, University of Pavia, Pavia, Italy
    Circulation 127:1009-17. 2013
  4. ncbi Molecular and genetic basis of sudden cardiac death
    Alfred L George
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Clin Invest 123:75-83. 2013
  5. ncbi Leaky channels make weak muscles
    Alfred L George
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Clin Invest 122:4333-6. 2012
  6. ncbi Strategy for encoding and comparison of gene expression signatures
    Yajun Yi
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    Genome Biol 8:R133. 2007
  7. ncbi SCN5A allelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr
    Stacy A S Killen
    Department of Medicine, Vanderbilt University, Nashville, TN, USA
    BMC Med Genet 11:74. 2010
  8. ncbi Web-based interrogation of gene expression signatures using EXALT
    Jun Wu
    Department of Medicine, Vanderbilt University, Nashville, TN 37232 0275, USA
    BMC Bioinformatics 10:420. 2009
  9. ncbi From stones to bones: the biology of ClC chloride channels
    A L George
    Department of Medicine, Division of Genetic Medicine, 451 Preston Research Building, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 6304, USA
    Curr Biol 11:R620-8. 2001
  10. ncbi Molecular basis of inherited epilepsy
    Alfred L George
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232-0275, USA
    Arch Neurol 61:473-8. 2004

Research Grants

  1. Genetic Modifiers of Congenital Long QT Syndrome
    ALFRED GEORGE; Fiscal Year: 2005
  2. Neonatal Long QT Syndrome and Sudden Infant Death
    Alfred L George; Fiscal Year: 2010
  3. Genetic Modifiers of Congenital Long QT Syndrome
    ALFRED GEORGE; Fiscal Year: 2007
  4. Neonatal Long QT Syndrome and Sudden Infant Death
    ALFRED GEORGE; Fiscal Year: 2007
  5. TRAINING PROGRAM IN ION CHANNEL AND TRANSPORTER BIOLOGY
    ALFRED GEORGE; Fiscal Year: 2007
  6. Molecular Physiology of KCNE Potassium Channel Subunits
    ALFRED GEORGE; Fiscal Year: 2007
  7. Transcriptional remodeling in cardiac arrhythmias
    ALFRED GEORGE; Fiscal Year: 2005
  8. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    ALFRED GEORGE; Fiscal Year: 2007
  9. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    Alfred L George; Fiscal Year: 2010
  10. Neonatal Long QT Syndrome and Sudden Infant Death
    ALFRED GEORGE; Fiscal Year: 2009

Detail Information

Publications81

  1. ncbi Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks)
    Andrew L Lundquist
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Mol Cell Cardiol 38:277-87. 2005
    ....
  2. ncbi Single-channel properties of human NaV1.1 and mechanism of channel dysfunction in SCN1A-associated epilepsy
    Carlos G Vanoye
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA
    J Gen Physiol 127:1-14. 2006
    ....
  3. ncbi Calmodulin mutations associated with recurrent cardiac arrest in infants
    Lia Crotti
    Section of Cardiology, Department of Molecular Medicine, University of Pavia, Pavia, Italy
    Circulation 127:1009-17. 2013
    ..We performed exome sequencing on 2 unrelated infants presenting with recurrent cardiac arrest to discover a genetic cause...
  4. ncbi Molecular and genetic basis of sudden cardiac death
    Alfred L George
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Clin Invest 123:75-83. 2013
    ..This Review presents an overview of the molecular basis of SCD, with a focus on monogenic arrhythmia syndromes...
  5. ncbi Leaky channels make weak muscles
    Alfred L George
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Clin Invest 122:4333-6. 2012
    ..Their work advances understanding of molecular and cellular mechanisms underlying an inherited channelopathy...
  6. ncbi Strategy for encoding and comparison of gene expression signatures
    Yajun Yi
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    Genome Biol 8:R133. 2007
    ..This novel approach to performing global comparisons of shared microarray data may have enormous value when coupled directly with a shared data repository...
  7. ncbi SCN5A allelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr
    Stacy A S Killen
    Department of Medicine, Vanderbilt University, Nashville, TN, USA
    BMC Med Genet 11:74. 2010
    ..We hypothesized that some heterozygous carriers may have unequal expression of wild-type and variant alleles and secondarily that predominance of the variant gene copy could further increase risk for sudden death in this population...
  8. ncbi Web-based interrogation of gene expression signatures using EXALT
    Jun Wu
    Department of Medicine, Vanderbilt University, Nashville, TN 37232 0275, USA
    BMC Bioinformatics 10:420. 2009
    ..Integration and exploration of these complex and heterogeneous data have become a major challenge...
  9. ncbi From stones to bones: the biology of ClC chloride channels
    A L George
    Department of Medicine, Division of Genetic Medicine, 451 Preston Research Building, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 6304, USA
    Curr Biol 11:R620-8. 2001
    ..These recent findings have demonstrated many eclectic functions of ClC channels and have placed Cl(-) channels in the physiological limelight...
  10. ncbi Molecular basis of inherited epilepsy
    Alfred L George
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232-0275, USA
    Arch Neurol 61:473-8. 2004
  11. ncbi Inherited disorders of voltage-gated sodium channels
    Alfred L George
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    J Clin Invest 115:1990-9. 2005
    ....
  12. ncbi Common genetic variants in sudden cardiac death
    Alfred L George
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    Heart Rhythm 6:S3-9. 2009
    ....
  13. ncbi 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...
  14. ncbi Malignant perinatal variant of long-QT syndrome caused by a profoundly dysfunctional cardiac sodium channel
    Dao W Wang
    Department of Medicine, Vanderbilt University, Nashville, TN 37232 0275, USA
    Circ Arrhythm Electrophysiol 1:370-8. 2008
    ....
  15. ncbi Cardiac sodium channel dysfunction in sudden infant death syndrome
    Dao W Wang
    Departments of Pharmacology, Vanderbilt University, Nashville, Tenn, USA
    Circulation 115:368-76. 2007
    ..We present functional characterization of 7 missense variants (S216L, R680H, T1304M, F1486L, V1951L, F2004L, and P2006A) and 1 in-frame deletion allele (delAL586-587) identified by these efforts...
  16. ncbi 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...
  17. ncbi Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia
    Thao P Nguyen
    Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
    Circ Res 102:364-71. 2008
    ....
  18. ncbi Epilepsy-associated dysfunction in the voltage-gated neuronal sodium channel SCN1A
    Christoph Lossin
    Neuroscience Graduate Program, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    J Neurosci 23:11289-95. 2003
    ..In conclusion, our data provide evidence for a wide spectrum of sodium channel dysfunction in familial epilepsy and demonstrate that both GEFS+ and SMEI can be associated with nonfunctional SCN1A alleles...
  19. ncbi Sodium channel dysfunction in intractable childhood epilepsy with generalized tonic-clonic seizures
    Thomas H Rhodes
    Division of Genetic Medicine, Department of Medicine, 529 Light Hall, Vanderbilt University, 2215 Garland Avenue, Nashville, TN 37232 0275, USA
    J Physiol 569:433-45. 2005
    ..The constellation of biophysical abnormalities for some mutants is distinct from those previously observed for GEFS+ and SMEI, suggesting possible, but complex, genotype-phenotype correlations...
  20. ncbi 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
    ....
  21. ncbi Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European- and African-American men and women
    Michael D Floyd
    Division of Clinical Pharmacology, Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 6602, USA
    Pharmacogenetics 13:595-606. 2003
    ..In most healthy subjects, variability in intestinal and hepatic CYP3A activity, using midazolam as an in-vivo probe, is modest and common polymorphisms in CYP3A4 and CYP3A5 do not appear to have important functional significance...
  22. ncbi Extracellular sodium interacts with the HERG channel at an outer pore site
    Franklin M Mullins
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Gen Physiol 120:517-37. 2002
    ..We also examined the role of the HERG closed state in Na(+)(o) inhibition. Na(+)(o) inhibition was inversely related to pulsing frequency in the WT channel, but not in the pore mutant S624A...
  23. ncbi Divergent sodium channel defects in familial hemiplegic migraine
    Kristopher M Kahlig
    Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, TN 37240, USA
    Proc Natl Acad Sci U S A 105:9799-804. 2008
    ..1 defects can cause FHM3. Our results also emphasize the complex relationship between migraine and epilepsy and provide further evidence that both disorders may share common molecular mechanisms...
  24. ncbi Exaggerated Mg2+ inhibition of Kir2.1 as a consequence of reduced PIP2 sensitivity in Andersen syndrome
    Leomar Y Ballester
    Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    Channels (Austin) 1:209-17. 2007
    ..1 channels. Our data also indicate that a single mutant subunit is sufficient to explain dominant-negative behavior of Kir2.1-T74A in Andersen syndrome...
  25. ncbi Pharmacogenetics of long-term responses to antiretroviral regimens containing Efavirenz and/or Nelfinavir: an Adult Aids Clinical Trials Group Study
    David W Haas
    Vanderbilt University School of Medicine, Nashville, TN 37203, USA
    J Infect Dis 192:1931-42. 2005
    ..Nelfinavir is a substrate for P-glycoprotein, which is encoded by MDR1. The present study examined associations between genetic variants and long-term responses to treatment...
  26. ncbi Haplotype diversity in four genes (CLCNKA, CLCNKB, BSND, NEDD4L) involved in renal salt reabsorption
    Saba Sile
    Department of Medicine, Vanderbilt University, Nashville, Tenn 37232 0275, USA
    Hum Hered 65:33-46. 2008
    ....
  27. ncbi Drug transporter and metabolizing enzyme gene variants and nonnucleoside reverse-transcriptase inhibitor hepatotoxicity
    Marylyn D Ritchie
    Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Clin Infect Dis 43:779-82. 2006
    ..Decreased risk of hepatotoxicity was associated with MDR1 3435C-->T (odds ratio, 0.254; P=.021). An interaction between MDR1 and hepatitis B surface antigen status predicted risk with 82% accuracy (P<.001)...
  28. ncbi Impaired inactivation gate stabilization predicts increased persistent current for an epilepsy-associated SCN1A mutation
    Kristopher M Kahlig
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    J Neurosci 26:10958-66. 2006
    ....
  29. ncbi Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation
    Dawood Darbar
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
    Circulation 117:1927-35. 2008
    ..Here, we tested the hypothesis that vulnerability to AF is associated with variation in SCN5A, the gene encoding the cardiac sodium channel...
  30. ncbi KCNQ1/KCNE1 assembly, co-translation not required
    Carlos G Vanoye
    Department of Medicine, Vanderbilt University, Nashville, TN, USA
    Channels (Austin) 4:108-14. 2010
    ....
  31. ncbi Functional BSND variants in essential hypertension
    Saba Sile
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    Am J Hypertens 20:1176-1182. 2007
    ..Sodium chloride reabsorption in the thick ascending limb (TAL) is dependent in part on the chloride channel, ClC-Kb (encoded by CLCNKB), and its accessory subunit, barttin (encoded by BSND)...
  32. ncbi CLCNKB-T481S and essential hypertension in a Ghanaian population
    Saba Sile
    Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    J Hypertens 27:298-304. 2009
    ..In this study, we re-examined CLCNKB-T481S using a large homogenous population from Ghana, and coupled genetic analyses with the functional characterization of this polymorphism using a mammalian expression system...
  33. ncbi Congenital long QT syndrome aggravated by salt-wasting nephropathy
    Dawood Darbar
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37323, USA
    Heart Rhythm 2:304-6. 2005
  34. ncbi Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block
    Dao W Wang
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Pediatrics, Medical University of South Carolina, Charleston, USA
    Circulation 105:341-6. 2002
    ..These data provide insight into the distinct clinical phenotypes resulting from mutation of a single ion channel...
  35. ncbi Functional interaction between extracellular sodium, potassium and inactivation gating in HERG channels
    Franklin M Mullins
    Room 560 PRB MRB II, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Physiol 558:729-44. 2004
    ..While a model with only a single dynamic Na(+)(o) site was inadequate, a model with two distinct Na(+)(o) sites was sufficient to reproduce the data...
  36. ncbi Noninactivating voltage-gated sodium channels in severe myoclonic epilepsy of infancy
    Thomas H Rhodes
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 101:11147-52. 2004
    ..Our results further indicate that a complex relationship exists between phenotype and aberrant sodium channel function in these inherited epilepsies...
  37. ncbi 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...
  38. ncbi Tissue factor and platelet glycoprotein Ib-alpha alleles are associated with age at first coronary bypass operation
    Brian S Donahue
    Department of Anesthesiology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Anesthesiology 99:1287-94. 2003
    ..The authors tested this hypothesis in a cardiac surgery population...
  39. ncbi Factor V Leiden protects against blood loss and transfusion after cardiac surgery
    Brian S Donahue
    Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tenn 37232, USA
    Circulation 107:1003-8. 2003
    ....
  40. ncbi 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...
  41. ncbi 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)...
  42. ncbi 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...
  43. ncbi Heterologous expression of ion channels
    Andrew R Tapper
    Department of Pharmacology, Vanderbilt University, Nashville, TN, USA
    Methods Mol Biol 217:285-94. 2003
  44. ncbi Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome
    Leomar Y Ballester
    Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37027 0275, USA
    Hum Mutat 27:388. 2006
    ..C101R) exhibited impaired trafficking. Our results demonstrate functional consequences of two novel trafficking-competent KCNJ2 mutations associated with Andersen syndrome and expand our knowledge of allelic diversity in this disease...
  45. ncbi Polymorphisms in beta-adrenergic receptor genes in the acquired long QT syndrome
    Hideaki Kanki
    Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 6602, USA
    J Cardiovasc Electrophysiol 13:252-6. 2002
    ....
  46. ncbi Molecular basis of an inherited epilepsy
    Christoph Lossin
    Division of Genetic Medicine, Center for Molecualr Neurosciences, Vanderbilt University, Nashville, TN 37232, USA
    Neuron 34:877-84. 2002
    ..This gain-of-function abnormality will likely enhance excitability of neuronal membranes by causing prolonged membrane depolarization, a plausible underlying biophysical mechanism responsible for this inherited human epilepsy...
  47. ncbi 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...
  48. ncbi KCNE4 domains required for inhibition of KCNQ1
    Lauren J Manderfield
    Department of Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232 0275, USA
    J Physiol 587:303-14. 2009
    ..We further demonstrated that the KCNE4 C-terminus interacts with KCNQ1. Our data reveal important structure-function relationships for KCNE4 that help advance our understanding of potassium channel modulation by KCNE proteins...
  49. ncbi Nonfunctional SCN1A is common in severe myoclonic epilepsy of infancy
    Iori Ohmori
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    Epilepsia 47:1636-42. 2006
    ..Here we report the functional characterization of eight SCN1A mutations (G177E, I227S, R393H, Y426N, H939Q, C959R, delF1289, and T1909I) previously identified in SMEI probands...
  50. ncbi Impaired NaV1.2 function and reduced cell surface expression in benign familial neonatal-infantile seizures
    Sunita N Misra
    Department of Pharmacology, Division of GeneticMedicine, Vanderbilt University, Nashville, Tennessee 37232 0275, USA
    Epilepsia 49:1535-45. 2008
    ..Functional characterization of three BFNIS mutations was performed to identify defects in channel function that underlie this disease...
  51. ncbi Preparation, functional characterization, and NMR studies of human KCNE1, a voltage-gated potassium channel accessory subunit associated with deafness and long QT syndrome
    Changlin Tian
    Department of Biochemistry, Center for Structural Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8725, USA
    Biochemistry 46:11459-72. 2007
    ..Given that this segment overlaps with sites 57-59, which are known to play a critical role in modulating KCNQ1 channel activation kinetics, this unusual structural feature likely has considerable functional relevance...
  52. ncbi Novel SCN1A frameshift mutation with absence of truncated Nav1.1 protein in severe myoclonic epilepsy of infancy
    Erin J McArdle
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee
    Am J Med Genet A 146:2421-3. 2008
  53. ncbi KCNE4 can co-associate with the I(Ks) (KCNQ1-KCNE1) channel complex
    Lauren J Manderfield
    Department of Pharmacology, Vanderbilt University, 2215 Garland Avenue, Nashville, TN 37232, USA
    FEBS J 275:1336-49. 2008
    ..The observation that multiple KCNE proteins can co-associate with and modulate KCNQ1 channels to produce biochemically diverse channel complexes has important implications for understanding K(V) channel regulation in human physiology...
  54. ncbi Molecular physiology of renal ClC chloride channels/transporters
    Saba Sile
    Department of Medicine, Division of Genetic Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0275, USA
    Curr Opin Nephrol Hypertens 15:511-6. 2006
    ..New insights into fundamental structure-function relationships, mechanisms of ion translocation, cellular regulation, and roles in human disease have increased attention on ClC proteins as important potential therapeutic targets...
  55. ncbi Functional characterization of recombinant human ClC-4 chloride channels in cultured mammalian cells
    Carlos G Vanoye
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Physiol 539:373-83. 2002
    ..This detailed characterization will be highly valuable in comparisons of hClC-4 function with native chloride channel activities and for future structure-function correlations...
  56. ncbi Distinct subdomains of the KCNQ1 S6 segment determine channel modulation by different KCNE subunits
    Carlos G Vanoye
    Division of Genetic Medicine, Department of Medicine, Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA
    J Gen Physiol 134:207-17. 2009
    ....
  57. ncbi Multiplexed transposon-mediated stable gene transfer in human cells
    Kristopher M Kahlig
    Department of Medicine, Vanderbilt University, Nashville, TN 37235, USA
    Proc Natl Acad Sci U S A 107:1343-8. 2010
    ....
  58. ncbi Molecular, functional, and genomic characterization of human KCC2, the neuronal K-Cl cotransporter
    Luyan Song
    Department of Medicine, Nashville VA Medical Center and Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Brain Res Mol Brain Res 103:91-105. 2002
    ..3+/-1.8 mM and 6.8+/-0.9 mM, respectively; both affinities are significantly higher than KCC1 and KCC4. The K(m) for Cl(-) is close to the intracellular Cl(-) activity of mature neurons, as befits a neuronal efflux mechanism...
  59. ncbi Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel
    Congbao Kang
    Department of Biochemitry, Vanderbilt University, Nashville, Tennessee 37232, USA
    Biochemistry 47:7999-8006. 2008
    ..These working models for the KCNE1-KCNQ1 complexes may be used to formulate testable hypotheses for the molecular bases of disease phenotypes associated with the dozens of known inherited mutations in KCNE1 and KCNQ1...
  60. ncbi Coupled analysis of gene expression and chromosomal location
    Yajun Yi
    Division of Genetic Medicine, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TX 37232, USA
    Genomics 85:401-12. 2005
    ..We conclude that DIGMAP is a powerful computational tool enabling the coupled analysis of microarray data with genome location...
  61. ncbi Improved DNA sequencing quality and efficiency using an optimized fast cycle sequencing protocol
    Adam R Platt
    Vanderbilt University, Nashville, TN 37232, USA
    Biotechniques 43:58, 60, 62. 2007
  62. ncbi Functional repair of a mutant chloride channel using a trans-splicing ribozyme
    Christopher S Rogers
    Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
    J Clin Invest 110:1783-9. 2002
    ..These results indicate that RNA repair can restore wild-type protein activity and reveal considerable cell-to-cell variability in ribozyme-mediated trans-splicing reaction efficiency...
  63. ncbi Expression and transcriptional control of human KCNE genes
    Andrew L Lundquist
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Genomics 87:119-28. 2006
    ....
  64. ncbi Fibrocystin/polyductin modulates renal tubular formation by regulating polycystin-2 expression and function
    Ingyu Kim
    Division of Genetic Medicine, Department of Medicine and Cell and Developmental Biology, Vanderbilt University, 539 LH, 2215 Garland Avenue, Nashville, TN 37232, USA
    J Am Soc Nephrol 19:455-68. 2008
    ..It is concluded that a functional and molecular interaction exists between FPC and PC2 in vivo...
  65. ncbi Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block
    Jean Francois Desaphy
    Division of Pharmacology, Department of Pharmaco Biology, University of Bari, Bari I 70125, Italy
    J Physiol 554:321-34. 2004
    ..This study offers a pharmacogenetic strategy to better address treatment in individual myotonic patients...
  66. ncbi Prevalence of long-QT syndrome gene variants in sudden infant death syndrome
    Marianne Arnestad
    Institute of Forensic Medicine, University of Oslo, Oslo, Norway
    Circulation 115:361-7. 2007
    ..Given the importance and potential implications of these observations, we performed a study to more accurately quantify the contribution to SIDS of LQTS gene mutations and rare variants...
  67. ncbi Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype
    Li Zhang
    LDS Hospital, 324 10th Ave, Suite 130, Salt Lake City, Utah 84103, USA
    Circulation 111:2720-6. 2005
    ..The normal QTc, distinct ECG, and other clinical features distinguish ATS1 from long-QT syndrome, and it is best designated as ATS1 rather than LQT7...
  68. ncbi Hybrid assemblies of ATP-sensitive K+ channels determine their muscle-type-dependent biophysical and pharmacological properties
    Domenico Tricarico
    Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, via Orabona no. 4, 70120 Bari, Italy
    Proc Natl Acad Sci U S A 103:1118-23. 2006
    ..Muscle-specific K(ATP) subunit compositions contribute to the physiological performance of different muscle fiber types and determine the pharmacological actions of drugs modulating K(ATP) activity in muscle diseases...
  69. ncbi Phenotypic variability and unusual clinical severity of congenital long-QT syndrome in a founder population
    Paul A Brink
    Department of Internal Medicine, University of Stellenbosch, South Africa
    Circulation 112:2602-10. 2005
    ..We are investigating one such founder effect, originating in South Africa in approximately ad 1700 and segregating the same KCNQ1 mutation (A341V)...
  70. ncbi KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes
    Gregor Andelfinger
    Department of Pediatrics, Children s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, 45229, USA
    Am J Hum Genet 71:663-8. 2002
    ..1 current. These findings support the suggestion that, in addition to its recognized role in function of cardiac and skeletal muscle, KCNJ2 plays an important role in developmental signaling...
  71. ncbi The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum
    Heidi C Howard
    Centre for Research in Neuroscience, McGill University and The Montreal General Hospital Research Institute, 1650 Cedar Ave, Montreal, Quebec H3G 1A4, Canada
    Nat Genet 32:384-92. 2002
    ..Our findings identify mutations in SLC12A6 as the genetic lesion underlying ACCPN and suggest a critical role for SLC12A6 in the development and maintenance of the nervous system...
  72. ncbi High-resolution mapping of the sodium channel modifier Scnm1 on mouse chromosome 3 and identification of a 1.3-kb recombination hot spot
    David A Buchner
    Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI 48109 0618, USA
    Genomics 82:452-9. 2003
    ..5 cM/Mb. The role of the modifier in other disorders in human and mouse can be tested with linked markers described here...
  73. ncbi 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
    ....
  74. ncbi KCNH2-K897T is a genetic modifier of latent congenital long-QT syndrome
    Lia Crotti
    Department of Cardiology, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy
    Circulation 112:1251-8. 2005
    ..CONCLUSIONS: We have provided evidence that a common KCNH2 polymorphism may modify the clinical expression of a latent LQT2 mutation. A similar mechanism may contribute to the risk for sudden death in more prevalent cardiac diseases...
  75. ncbi Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)
    D Woodrow Benson
    Department of Pediatrics, Cincinnati Children s Hospital, Ohio, USA
    J Clin Invest 112:1019-28. 2003
    ..Our findings reveal a molecular basis for some forms of congenital SSS and define a recessive disorder of a human heart voltage-gated sodium channel...
  76. ncbi Appraising the value of genomic association studies
    Alfred L George
    J Am Soc Nephrol 19:1840-2. 2008
  77. ncbi Reduced expression of Kir6.2/SUR2A subunits explains KATP deficiency in K+-depleted rats
    Domenico Tricarico
    Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, via Orabona no 4, 70120 Bari, Italy
    Neuromuscul Disord 18:74-80. 2008
    ..Kir6.2/SUR2A deficiency is associated with impaired muscle function in K(+)-depleted rats and in hypoPP...
  78. ncbi Change of chloride ion channel conductance is an early event of slow-to-fast fibre type transition during unloading-induced muscle disuse
    Sabata Pierno
    Sezione di Farmacologia, Dipartimento Farmaco-Biologico, , , Italy
    Brain 125:1510-21. 2002
    ..Pharmacological modulation of ClC-1 channels may help to prevent disuse-induced muscle impairment...
  79. ncbi Polymorphic ventricular tachycardia and KCNJ2 mutations
    Terrence U H Chun
    Division of Cardiology, Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
    Heart Rhythm 1:235-41. 2004
    ..Arrhythmia documented during cardiac arrest is rapid ventricular tachycardia; ICD is effective therapy for cardiac arrest in patients with PVT due to KCNJ2 mutation...
  80. ncbi Neural control of heart rate is an arrhythmia risk modifier in long QT syndrome
    Peter J Schwartz
    Section of Cardiology, Department of Lung, Blood and Heart, University of Pavia, Pavia, Italy
    J Am Coll Cardiol 51:920-9. 2008
    ....
  81. ncbi Mutant prenyltransferase-like mitochondrial protein (PLMP) and mitochondrial abnormalities in kd/kd mice
    Min Peng
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Kidney Int 66:20-8. 2004
    ..By testing for linkage to microsatellite markers, we previously localized the kd gene to a YAC/BAC contig...

Research Grants40

  1. Genetic Modifiers of Congenital Long QT Syndrome
    ALFRED GEORGE; Fiscal Year: 2005
    ..g. ischemic heart disease and congestive heart failure) that are burdened by a high incidence of SCD. ..
  2. Neonatal Long QT Syndrome and Sudden Infant Death
    Alfred L George; Fiscal Year: 2010
    ..Identifying factors, including genetic, that contribute to sudden unexpected death in infants has great importance for diagnosis and treatment of preventable causes of SIDS. ..
  3. Genetic Modifiers of Congenital Long QT Syndrome
    ALFRED GEORGE; Fiscal Year: 2007
    ..g. ischemic heart disease and congestive heart failure) that are burdened by a high incidence of SCO. ..
  4. Neonatal Long QT Syndrome and Sudden Infant Death
    ALFRED GEORGE; Fiscal Year: 2007
    ..Identifying factors, including genetic, that contribute to sudden unexpected death in infants has great importance for diagnosis and treatment of preventable causes of SIDS. ..
  5. TRAINING PROGRAM IN ION CHANNEL AND TRANSPORTER BIOLOGY
    ALFRED GEORGE; Fiscal Year: 2007
    ..The goal of the training program is to develop scientists with strong commitments to academic biomedical research in the area of ion channel and transporter biology. ..
  6. Molecular Physiology of KCNE Potassium Channel Subunits
    ALFRED GEORGE; Fiscal Year: 2007
    ..abstract_text> ..
  7. Transcriptional remodeling in cardiac arrhythmias
    ALFRED GEORGE; Fiscal Year: 2005
    ..These studies will provide new insights into the pathogenesis of arrhythmia susceptibility and contribute to identifying potential new targets for therapeutic interventions. ..
  8. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    ALFRED GEORGE; Fiscal Year: 2007
    ..abstract_text> ..
  9. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    Alfred L George; Fiscal Year: 2010
    ..abstract_text> ..
  10. Neonatal Long QT Syndrome and Sudden Infant Death
    ALFRED GEORGE; Fiscal Year: 2009
    ..Identifying factors, including genetic, that contribute to sudden unexpected death in infants has great importance for diagnosis and treatment of preventable causes of SIDS. ..
  11. Genetic Modifiers of Congenital Long QT Syndrome
    ALFRED GEORGE; Fiscal Year: 2009
    ..g. ischemic heart disease and congestive heart failure) that are burdened by a high incidence of SCO. ..
  12. VANDERBILT NIDDK BIOTECHNOLOGY CENTER
    ALFRED GEORGE; Fiscal Year: 2002
    ..Finally, we will implement plans for the timely sharing of new experimental approaches, technologies, and resources to the broader research community. ..
  13. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    ALFRED GEORGE; Fiscal Year: 2002
    ..A third area of investigation will be to define structural determinants of Na+ channel a-b1 subunit interactions. These studies will provide information regarding the structure and function of mammalian Na+ channels. ..
  14. HEREDITARY DEFECTS IN HUMAN CHLORIDE CHANNELS
    ALFRED GEORGE; Fiscal Year: 2001
    ..In addition, the applicant proposes to delineate the transmembrane topology of the CIC channel using a glycosylation tagging method that has previously been employed to generate a topological model of AMPA-type glutamate receptors. ..
  15. Genetic Modifiers of Congenital Long QT Syndrome
    Alfred L George; Fiscal Year: 2010
    ..g. ischemic heart disease and congestive heart failure) that are burdened by a high incidence of SCO. ..