A5078700778- Cardiac Fibrosis and Remodeling
- Cardiovascular Effects of Exercise
- Cardiac electrophysiology and arrhythmias
- Telomeres, Telomerase, and Senescence
- Cardiac Structural Anomalies and Repair
- Genomics and Rare Diseases
- Cardiovascular Function and Risk Factors
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Endoplasmic Reticulum Stress and Disease
- Conducting polymers and applications
- Congenital heart defects research
- Hearing, Cochlea, Tinnitus, Genetics
- Mitochondrial Function and Pathology
- Hereditary Neurological Disorders
- Autophagy in Disease and Therapy
- RNA regulation and disease
Brown University
2018-2023
John Brown University
2020-2023
Rhode Island Hospital
2018-2023
Providence College
2018-2022
Baylor College of Medicine
2014
Over 1200 recessive disease genes have been described in humans. The prevalence, allelic architecture, and per-genome load of pathogenic alleles these remain to be fully elucidated, as does the contribution DNA copy-number variants (CNVs) carrier status disease. We mined CNV data from 21,470 individuals obtained by array-comparative genomic hybridization a clinical diagnostic setting identify deletions encompassing or disrupting genes. identified 3212 heterozygous potential affecting 419...
The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the upstream LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), protein encoding regulator endosomal trafficking. However, it was not clear how might impact excitation. We investigated effect on voltage-gated sodium channel Nav1.5, which critical for depolarization. show overexpressed resulted in significant increase density...
Aging in humans is associated with a 10-40-fold greater incidence of sudden cardiac death from malignant tachyarrhythmia. We have reported that thiol oxidation ryanodine receptors (RyR2s) by mitochondria-derived reactive oxygen species (mito-ROS) contributes to defective Ca2+ homeostasis cardiomyocytes (CMs) aging rabbit hearts. However, mechanisms responsible for the increase mito-ROS heart remain poorly understood. Here we test hypothesis age-associated decrease autophagy major contributor...
Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little known about pro-arrhythmic changes aged animals. Senescent cells accumulate with age and accelerate age-associated diseases. interfere function outcome post-MI age, studies have not been performed larger the mechanisms are unknown. Specifically, timecourse of senescence related inflammation fibrosis understood. Additionally, cellular systemic...
Cardiac arrhythmias significantly contribute to cardiovascular morbidity and mortality. The rabbit heart serves as an accepted model system for studying cardiac cell excitation arrhythmogenicity. Accordingly, primary cultures of adult ventricular cardiomyocytes serve a preferable study molecular mechanisms human excitation. However, the use is often regarded excessively costly. Therefore, we developed characterized novel low-cost cardiomyocyte model, namely, 3-week-old (3wRbCMs). Ventricular...
Aging is associated with a more than 5‐ to 40‐fold increase in the incidence of sudden cardiac death. Our laboratory has established female New Zealand White rabbit as model aging heart, young (5–9 months) and old (4–6 years) rabbits recapitulate human pathophysiology. Previously we developed minimally invasive procedure involving coil embolization left coronary artery reproducibly induce myocardial infarction (MI) 25–35% ventricular free wall (Morrissey 2017). Aged experience increased...
Arrhythmogenic tissue remodeling after myocardial infarction (MI) has been well described in young animals, but how this wound healing process changes with age and leads to increased risk of sudden cardiac death (SCD) post‐MI is not understood. Cellular senescence an irreversible cell cycle arrest which regulates tumor suppression healing, however accumulation senescent cells various tissues thought drive aging pathology. We hypothesize that age, persistent myofibroblast (CMF) promotes...
Cellular senescence is a stress response characterized by irreversible cell cycle arrest, secretion of inflammatory cytokines and growth factors termed the “senescence associated secretory phenotype” (SASP), resistance to apoptosis. Senescence plays beneficial roles in tumor suppression, wound healing, development young animals, but thought underlie aging‐associated pathology numerous tissues, mainly via SASP. Our previous work aged rabbit myocardial infarction (MI) model demonstrated an...
Objectives Cellular senescence is a stress response involving permanent replicative arrest. It accompanied by complex senescence‐associated secretory phenotype (SASP), which characterized the presence of pro‐inflammatory cytokines and chemokines, growth factors, tissue‐remodeling metalloproteinases. Little known regarding role SASP in context arrhythmias post myocardial infarction (MI). Here, we arrhythmogenic cardiac consequences molecular mechanisms underlying tissue remodeling changes...
Abstract Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little known about pro-arrhythmic changes aged animals. Senescent cells accumulate with age and accelerate age-associated diseases. interfere function outcome post-MI age, studies have not been performed large the mechanisms are unknown. Here, we investigated role of senescence regulating inflammation, fibrosis, arrhythmogenesis infarcted...