Cardiology Research | Bezzerides Research Group

The Bezzerides Research Group (BRG) is focused on understanding the fundamental mechanisms of arrhythmia for improved clinical care and novel therapeutic development. Current areas of research include:

1. Gene therapy for inherited cardiovascular disease
2. Modeling of human cardiac disease with induced pluripotent stem cells (iPSCs)

Gene therapy for inherited cardiovascular disease

Sudden cardiac death (SCD) in the young is a devastating event for families and the surrounding community. Mutations in ion channels and related proteins can cause life-threatening arrhythmias leading to SCD. One particularly malignant inherited arrhythmia syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), is caused by exercise or stress. We have developed a gene therapy for this life-threatening disease, by inhibiting an aberrant signaling pathway in the heart. In addition to treating CPVT, this method may have utility in other forms of inherited and acquired heart disease.

Representative publications:

1. Bezzerides, V. J., Caballero, A., Wang, S., Ai, Y., Hylind, R. J., Lu, F., Heims-Waldron, D. A., Chambers, K. D., Zhang, D., Abrams, D. J. & Pu, W. T. Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia by Inhibition of Ca2+/Calmodulin-Dependent Kinase II. Circulation (2019). doi:10.1161/CIRCULATIONAHA.118.038514
2. Bezzerides VJ, Zhang A, Xiao L, Simonson B, Khedkar SA, Baba S, Ottaviano F, Lynch S, Hessler K, Rigby AC, Milan D, Das S, Rosenzweig A. Inhibition of serum and glucocorticoid regulated kinase-1 as novel therapy for cardiac arrhythmia disorders. Sci Rep 2017;7(1):346:1-13.

Modeling of human cardiac disease with induced pluripotent stem cells (iPSCs)

The development of techniques to create stem cells from patients has ushered in a new era of disease modeling for personalized medicine. We use patient-derived stem cells and genome editing techniques to create genetically accurate models of human disease. These models improve new mechanistic insights into disease pathogenesis and enable development of novel predictive models and therapies.

Representative publications:

1. Park S-J, Zhang D, Qi Y, Li Y, Lee KY, Bezzerides VJ, Yang P, Xia S, Kim SL, Liu X, Lu, F, Pasqualini FS, Campbell PH, Geva J, Roberts AE, Kleber AG, Abrams DJ, Pu WT, Parker KK. Insights into the pathogenesis of catecholaminergic polymorphic ventricular tachycardia from engineered human heart tissue. Circulation (in press).
2. Bezzerides VJ, Zhang D, Pu WT Modeling Inherited Arrhythmia Disorders Using Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Circ J. 2016;22(1):12-21.

Vassilios Bezzerides, MD, PhD Vassilios Bezzerides, MD, PhD, is an attending in the Electrophysiology Service and a Principal Investigator in the Basic and Translational Cardiovascular Research Division within the Department of Cardiology at Boston Children’s Hospital. Dr. Bezzerides has expertise in cellular, animal, and clinical electrophysiology, with a specific emphasis on ion channel biophysics and regulation. His lab is focused on the development of novel models of human disease for improved clinical outcome prediction and therapeutic development. Dr. Bezzerides completed a dual undergraduate degree in physics and biochemistry from the University of Washington in Seattle and an MD/PhD from the combined MIT/Harvard HST program. He trained in pediatrics and pediatric cardiology at Boston Children’s Hospital, with additional specialized training in clinical electrophysiology. He did his thesis with Dr. David Clapham and post-doctoral training with Dr. Anthony Rosenzweig and Dr. William Pu. In addition to basic research, Dr. Bezzerides sees patients with a clinical focus of inherited arrhythmia syndromes and cardiomyopathy. Contact: Vassilios.Bezzerides@cardio.chboston.org