Cardiac arrhythmias represent irregular heartbeats that disturb regular heart rhythm and can lead to sudden cardiac death (SCD). SCD due to malignant arrhythmias underliesr 15~20% of all deaths. The arrhythmia program at the Cardiovascular Research Center (CVRC) focuses its research on the molecular mechanisms of malignant cardiac arrhythmias using a myriad of in vivo and in vitro experimental research models. The in vivo models include congenital long QT syndrome in rabbits, mouse knockout models of proteins that participate in cell-cell interactions as well as ubiquitin ligases. We also study the aging rabbit heart for atrial arrhythmias and arrhythmias after minimally invasive infarction. The in vitro models include experimental heart tissues such as iPS derived atrial organoids as well as micro tissues of ventricular myocytes as cultured of primary myocytes derived from rabbits, rats and mice.
Using these in vivo and in vitro models our team investigates, mechano-transduction, ion channels trafficking, turnover, and plasma membrane localization. In addition, we study intracellular calcium handling, the role of cardiomyocytes and fibroblasts senescence in atrial and ventricular arrhythmias. Our organoids are used to study cardiotoxicity of investigational drugs. We are currently developing gene therapy for long QT syndrome as well as testing the role of senolytic drugs in preventing cardiac arrhythmias From single molecule to telemetry in vivo studies, the research group discovers new findings how ectopic rhythm originates from the intact heart leading to paradigm shift of understanding cardiac arrhythmia mechanisms in developing new therapeutic approaches.
The Heart Rhythm Disorder research group forms productive collaboration across the Rhode Island state, VA Medical Center, and Brown University in molecular biology, biomedical engineering and stem cell research to discover innovative therapeutic approaches for treating cardiac arrythmias within the clinical environment of the Rhode Island Hospital.
Related Publications
Transgenic rabbit models for cardiac disease research (https://pubmed.ncbi.nlm.nih.gov/33822374/)
Trafficking of the human ether-a-go-go-related gene (hERG) potassium channel is regulated by the ubiquitin ligase rififylin (RFFL) (https://pubmed.ncbi.nlm.nih.gov/30401747/)
Transient Outward K + Current (I to) Underlies the Right Ventricular Initiation of Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long-QT Syndrome Type 1 (https://pubmed.ncbi.nlm.nih.gov/29769222/)
A novel method of standardized myocardial infarction in aged rabbits (https://pubmed.ncbi.nlm.nih.gov/28213402/)
Principle Investigators
Dr. Gideon Koren
Laboratory: http://cvrc.brownmedicine.org/koren-lab/
Biography: https://vivo.brown.edu/display/gkoren
Dr. Bum-Rak Choi
Laboratory: http://cvrc.brownmedicine.org/choi-lab/
Biography: https://vivo.brown.edu/display/bc4#Research
