A5013560175- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Ion Transport and Channel Regulation
- Epilepsy research and treatment
- Receptor Mechanisms and Signaling
- Genetic Neurodegenerative Diseases
- Genomics and Rare Diseases
- Cardiac Arrhythmias and Treatments
- Cardiomyopathy and Myosin Studies
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Cardiovascular Effects of Exercise
- Cardiac pacing and defibrillation studies
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- Electrochemical Analysis and Applications
- Heart Rate Variability and Autonomic Control
- Neurological disorders and treatments
- Mitochondrial Function and Pathology
- Cardiac Arrest and Resuscitation
- ECG Monitoring and Analysis
- Pluripotent Stem Cells Research
Northwestern University
2016-2025
Children's Hospital Colorado
2024-2025
University of Colorado Denver
2024-2025
University of Kansas Medical Center
2025
Renal Research Institute
2023
Center for Autism and Related Disorders
2022-2023
University of California, Los Angeles
2022
Vanderbilt University
2008-2018
Vanderbilt University Medical Center
2000-2017
Center for Human Genetics
2006-2017
The principal voltage-sensitive sodium channel from human heart has been cloned, sequenced, and functionally expressed. cDNA, designated hH1, encodes a 2016-amino acid protein that is homologous to other members of the multigene family bears greater than 90% identity tetrodotoxin-insensitive characteristic rat immature denervated skeletal muscle. Northern blot analysis demonstrates an approximately 9.0-kilobase transcript expressed in atrial ventricular cardiac muscle but not adult muscle,...
Background — DNA variants appearing to predispose drug-associated “acquired” long-QT syndrome (aLQTS) have been reported in congenital disease genes. However, the incidence of these genetic risk factors has not systematically evaluated a large set patients with aLQTS. We previously identified functionally important genes encoding K + channel ancillary subunits 11% an aLQTS cohort. Methods and Results The coding regions pore-forming proteins KvLQT1, HERG, SCN5A were screened (1) same cohort...
Background— The hypothesis that some cases of sudden infant death syndrome (SIDS) could be caused by long-QT (LQTS) has been supported molecular studies. However, there are inadequate data regarding the true prevalence mutations in arrhythmia-susceptibility genes among SIDS cases. Given importance and potential implications these observations, we performed a study to more accurately quantify contribution LQTS gene rare variants. Methods Results— Molecular screening 7 ( KCNQ1 , KCNH2 SCN5A...
Drug-induced long QT syndrome (LQTS) is a prevalent disorder of uncertain etiology that predisposes to sudden death. KCNE2 encodes MinK-related peptide 1 (MiRP1), subunit the cardiac potassium channel I Kr has been associated previously with inherited LQTS. Here, we examine in 98 patients drug-induced LQTS, identifying three individuals sporadic mutations and patient sulfamethoxazole-associated LQTS who carried single-nucleotide polymorphism (SNP) found ≈1.6% general population. While mutant...
Sick sinus syndrome (SSS) describes an arrhythmia phenotype attributed to node dysfunction and diagnosed by electrocardiographic demonstration of bradycardia or arrest. Although frequently associated with underlying heart disease seen most often in the elderly, SSS may occur fetus, infant, child without apparent cause. In this setting, is presumed be congenital. Based on prior associations disorders cardiac rhythm conduction, we screened α subunit sodium channel (SCN5A) as a candidate gene...
Sick sinus syndrome (SSS) describes an arrhythmia phenotype attributed to node dysfunction and diagnosed by electrocardiographic demonstration of bradycardia or arrest. Although frequently associated with underlying heart disease seen most often in the elderly, SSS may occur fetus, infant, child without apparent cause. In this setting, is presumed be congenital. Based on prior associations disorders cardiac rhythm conduction, we screened α subunit sodium channel (SCN5A) as a candidate gene...
Transposons are mobile genetic elements that can be used to integrate transgenes into host cell genomes. The piggyBac transposon system has been for transgenesis of insects and germline mutagenesis in mice. We compared transposition activity with Sleeping Beauty (SB), a widely preclinical gene therapy studies. An engineered minimal length 5' 3' terminal repeats exhibited greater transfected cultured human cells than well-characterized hyperactive SB system. PiggyBac excision was very precise...
Life-threatening disorders of heart rhythm may arise during infancy and can result in the sudden tragic death a child. We performed exome sequencing on 2 unrelated infants presenting with recurrent cardiac arrest to discover genetic cause.We ascertained (probands) dramatically prolonged QTc interval who were both born healthy parents. The parent-child trios investigated use search for de novo variants. then follow-up candidate gene screening an independent cohort 82 subjects congenital...
Genetic studies have identified ion channel gene variants in families segregating atrial fibrillation (AF), the most common arrhythmia clinical practice. Here, we tested hypothesis that vulnerability to AF is associated with variation SCN5A, encoding cardiac sodium channel.
Human leukocyte antigen B (HLA-B) is a gene that encodes cell surface protein involved in presenting antigens to the immune system. The variant allele HLA-B*15:02 associated with an increased risk of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) response carbamazepine treatment. We summarize evidence from published literature supporting this association provide recommendations for use based on HLA-B genotype (also available PharmGKB: http://www.pharmgkb.org). purpose...
The variant allele HLA‐B*15:02 is strongly associated with greater risk of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients treated carbamazepine or oxcarbazepine. HLA‐A*31:01 maculopapular exanthema, drug reaction eosinophilia systemic symptoms, SJS/TEN carbamazepine. We summarize evidence from the published literature supporting these associations provide recommendations for oxcarbazepine use based on HLA genotypes.
Abstract Aims Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1–3) that encode identical calmodulin proteins. We established International Calmodulinopathy Registry (ICalmR) to understand natural history, clinical features, response therapy patients with a CALM-mediated syndrome. Methods results A dedicated Case Report File was created collect demographic, clinical, genetic...
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia treatable with antiarrhythmic drugs; however, patient responses remain highly variable. Human induced pluripotent stem cell–derived atrial cardiomyocytes (iPSC-aCMs) are useful for discovering precision therapeutics, but current platforms yield phenotypically immature cells and not easily scalable high-throughput screening. Here, primary adult atrial, ventricular, fibroblasts greater functional iPSC-aCM maturation,...