Vassilios J. Bezzerides, MD, PhD

Assistant Professor of Pediatrics, Cardiology Department
Boston Children's Hospital, Harvard Medical School
300 Longwood Avenue, Boston Children's Hospital, Enders 1276 Boston, MA 02115
bezzerides@cardio.chboston.org
Bezzerides Laboratory Website

My research is focused on developing model systems to gain fundamental insights in disease mechanisms within the heart and the brain.

Using induced pluripotent stem cells (iPSCs) and genome editing, we create human disease models caused by ion channels, ion channel-related genes, or structural proteins. With the application of single-cell electrophysiology, optogenetics, and high-throughput imaging, we probe the consequences of protein dysfunction caused by pathogenic variants. Additionally, with our disease models, we are able to design targeted therapies for eventual translation to humans.

My lab is also interested in disease mechanisms common to excitable cells. As an example, the ryanodine receptor type 2 (RYR2) is an intracellular calcium reselase channel that is critical for excitation-contraction coupling in the heart, is also expressed in the brain. We have identified specific memory defects in mouse models that harbor pathogenic human mutations associated with the inherited arrhythmia syndrome, cathecholameranigic polymorphic ventricular tachycardia (CPVT). Ablation of a specific phosphorylation site for CaMKII on the same allele as a pathogenic CPVT mutation reversed the stereotypical arrhythmia phenotype. However, neurobehavioral testing of animals harboring both the activating and protective mutations continued to show specific short-term memory defects suggesting a different mechanism within the brain. 

In parallel research, we have used our model systems to develop novel therapeutics using high-speed/high-throughput imaging and computational approaches. We have developed a novel gene therapy based on structural analysis of the RYR2 channel and identified a previously approved oncologic agent repurposed as CaMKII inhibitor for treatment of arrhythmia patients.

PhD Dissertation Title:  Rapid Translocation of TRP Channels: Implications for Growth Cone Motility PhD Dissertation Advisor(s): Dr. David E. Clapham, Dept. of Cardiology, Boston Children's Hospital/ Harvard Medical School