A5004357254- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- Ion channel regulation and function
- Viral Infections and Immunology Research
- Congenital heart defects research
- Congenital Heart Disease Studies
- Genomics and Rare Diseases
- Cardiovascular Function and Risk Factors
- Chemotherapy-induced cardiotoxicity and mitigation
- Cardiac Arrhythmias and Treatments
- Ion Transport and Channel Regulation
- Cardiac Valve Diseases and Treatments
- Chronic Myeloid Leukemia Treatments
- Childhood Cancer Survivors' Quality of Life
- Cardiac pacing and defibrillation studies
- Mitochondrial Function and Pathology
- Chronic Lymphocytic Leukemia Research
- BRCA gene mutations in cancer
- Signaling Pathways in Disease
- Lysosomal Storage Disorders Research
- Genetic Associations and Epidemiology
- Muscle Physiology and Disorders
- Glycogen Storage Diseases and Myoclonus
- CRISPR and Genetic Engineering
Duke University
2018-2025
Duke University Hospital
2024
Duke Medical Center
2021-2024
American Society of Human Genetics
2022
Albert Einstein College of Medicine
2021
Baylor College of Medicine
2011-2020
Texas Children's Hospital
2014-2019
Baylor Genetics
2017
West German Heart and Vascular Center Essen
2017
Cardiovascular Institute Hospital
2015
Excitation-contraction coupling in striated muscle requires proper communication of plasmalemmal voltage-activated Ca2+ channels and release on sarcoplasmic reticulum within junctional membrane complexes. Although previous studies revealed a loss complexes embryonic lethality germ-line junctophilin-2 (JPH2) knockout mice, it has remained unclear whether JPH2 plays an essential role complex formation the Ca(2+)-induced Ca(2+) process heart. Our recent work demonstrated loss-of-function...
Transverse tubules (TTs) provide the basic subcellular structures that facilitate excitation–contraction (EC) coupling, essential process underlies normal cardiac contractility. Previous studies have shown TTs develop within first few weeks of life in mammals but molecular determinants this development remained elusive. This study aims to elucidate role junctophilin-2 (JPH2), a junctional membrane complex protein, maturation cardiomyocytes. Using novel cardiac-specific...
Genetic diseases that affect the cardiovascular system are relatively common and include cardiac channelopathies, cardiomyopathies, aortopathies, hypercholesterolemias, structural of heart great vessels. The rapidly expanding availability clinical genetic testing leverages decades research into origins these diseases, helping inform diagnosis, management, prognosis. Although a number guidelines statements detail best practices for testing, there is paucity pediatric-focused addressing unique...
Arrhythmogenic cardiomyopathy (ACM) is a primary disease of the myocardium, predominantly caused by genetic defects in proteins cardiac intercalated disc, particularly, desmosomes. Transmission mostly autosomal dominant with incomplete penetrance. ACM also has wide phenotype variability, ranging from premature ventricular contractions to sudden death and heart failure. Among other drivers modulators phenotype, inflammation response viral infection immune triggers have been postulated be an...
Background: There is a paucity of data regarding the phenotype dilated cardiomyopathy (DCM) gene variants in general population. We aimed to determine frequency and penetrance DCM-associated putative pathogenic adult population, with focus on expression clinical subclinical phenotype, including structural, functional, arrhythmic disease features. Methods: UK Biobank participants who had undergone whole exome sequencing, ECG, cardiovascular magnetic resonance imaging were selected for study....
BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is one of the leading causes sudden cardiac death in children, young adults, and athletes characterized by fibro-fatty replacement myocardium, predominantly right ventricle. Sixty percent patients with ACM have a known genetic cause, but for remainder, etiology unknown. This lack mechanistic understanding has also slowed development disease-modifying therapies, children high degree morbidity mortality. METHODS: Induced pluripotent stem cells...
Importance Alternating hemiplegia of childhood (AHC) is a disorder that can result from pathogenic variants in ATP1A3 -encoded sodium-potassium adenosine triphosphatase alpha 3 (ATP1A3). While AHC primarily neurologic disease, some individuals experience sudden unexplained death (SUD) potentially associated with cardiac arrhythmias. Objective To determine the impact on electrophysiology and whether lethal ventricular arrhythmias are SUD patients AHC. Design, Setting, Participants In this...
Background— Junctophilin-2 (JPH2), a protein expressed in the junctional membrane complex, is necessary for proper intracellular calcium (Ca 2+ ) signaling cardiac myocytes. Downregulation of JPH2 expression model hypertrophy was recently associated with defective coupling between plasmalemmal L-type Ca channels and sarcoplasmic reticular ryanodine receptors. However, it remains unclear whether altered patients hypertrophic cardiomyopathy (HCM). In addition, effects downregulation on...
Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners are also implicated resealing: caveolin-3 (in limb girdle type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin accumulates at sites damage, MG53-knockout mice display a progressive dystrophy. This study explored expression localization MG53 human skeletal muscle, how repair proteins modulated various forms dystrophy, whether is...
Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration.Patients either presumed autosomal dominant (N = 229) or recessive Type 2 Jervell Lange-Nielsen 19) were enrolled from 22 arrhythmia clinics 4 registries 9 countries. evaluated for ECG penetrance (defined as QTc...