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Grace Blair's Dissertation Defense (4/18/2023): Investigating the Coordination of Cardiac Conduction and Repolarization in Ventricular Myocardium

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Grace Blair

Dissertation Defense: Investigating the Coordination of Cardiac Conduction and Repolarization in Ventricular Myocardium

Grace Blair

Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Poelzing Lab, Fralin Biomedical Research Institute at VTC
April 18, 2023 at 3 p.m.,  Room G101 A/B, 4 Riverside Circle
Visit the Poelzing Lab

About this Dissertation

The ability of the heart to function as a pump is dependent on the successful coordination of electrical activity throughout the heart. Disruptions to this intricate electrical system result in cardiac arrythmias, which in turn prevent the heart from effectively perfusing the body with oxygenated blood. This dissertation investigates ways in which we can modulate cell-cell communication within the heart and how this may in turn influence disease states with a high propensity for arrhythmia. Grace Blair, working in the Poelzing Lab, shows that reducing electrical coupling between cells using simple interventions like reducing serum sodium or increasing osmolarity may be a viable technique for diagnosing “concealed” disease states (i.e. disease states that are asymptomatic for much of a patient’s life). Blair and the lab then explore ways in which elevated serum potassium, known as hyperkalemia, may alter the heart’s ability to recover from electrical activation (repolarization). Finally, Blair's research shows that the relationship between cardiac activation and repolarization is not as dependent on cell-cell communication as was once thought.

Taken together, this dissertation provides evidence that transiently disrupting cell-cell communication may hold promise for development of diagnostics for some congenital cardiac diseases, and yet does not appear to disrupt the relationship between electrical conduction and repolarization across the heart.  

More About the Candidate and Project

Education

Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate

University of North Carolina - Chapel Hill, B.S., Biology

Training

Graduate Research Assistant, Poelzing Lab, Fralin Biomedical Research Instittue at VTC

Mentor

Steven Poelzing, Ph.D., Professor, Fralin Biomedical Research Institute, Co-Director, Translational Biology, Medicine, and Health Graduate Program

Committee Members

  • Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship F31. Unmasking Conduction Deficits in the Scn5a+/- Mouse Model of Brugada Syndrome - 2021-2023

Grace Blair, Xiaobo Wu, Chandra B. Bain, Gregory Hoeker, Steve Poelzing. Mannitol and hyponatremia regulate cardiac ventricular conduction in the context of sodium channel loss of function. Manuscript submitted for publication. 

Grace Blair, Madeline Depman, William Adams, Elina Baltins, Greg Hoeker, Seth Weinberg, Steve Poelzing. Sequence-Dependent Repolarization in Ventricular Myocardium is More Dependent on Endogenous APD Gradients than Electrical Coupling. Manuscript submitted for publication. 

Tristan B. Raisch PhD, William P. Adams, Yajun Zhao PhD, Rafael Davalos PhD, Sarah Barrett DVM, PhD, DACVP4, D. Ryan King PhD, Chandra B. Bain, Katrina Colucci-Chang, Grace A. Blair, Rengasayee Veeraraghavan PhD, Xiaoping Wan MD,PhD, Isabelle Deschenes PhD, James W. Smyth PhD, Gregory S. Hoeker PhD, Robert G. Gourdie PhD, Steven Poelzing PhD. Extracellular perinexal separation is a principal determinant of cardiac conduction. Manuscript in review.

Rachel L. Padget, Grace A. Blair, Michael D. North, Michael J. Zeitz, Mira T. Tanenbaum, D. Ryan King, Gregory S. Hoeker, Sharon A. Swanger, Steven Poelzing, James W. Smyth. Acute adenoviral cardiac infection elicits an arrhythmogenic substrate prior to inflammatory myocardial remodeling and myocarditis. bioRxiv 2022.11.29.518421; doi: https://doi.org/10.1101/2022.11.29.518421

Lin J, Abraham A, George SA, Greer-Short A, Blair GA, Moreno A, Alber BR, Kay MW, Poelzing S. Ephaptic Coupling Is a Mechanism of Conduction Reserve During Reduced Gap Junction Coupling. Front Physiol. 2022 May 5; 13:848019. PMID: 35600295.

Wu X, Hoeker GS, Blair GA, King DR, Gourdie RG, Weinberg SH, Poelzing S. Hypernatremia and intercalated disc edema synergistically exacerbate long-QT syndrome type 3 phenotype. Am J Physiol Heart Circ Physiol. 2021 Dec 1; 321(6):H1042-H1055. PMID: 34623182.

King DR, Entz M 2nd, Blair GA, Crandell I, Hanlon AL, Lin J, Hoeker GS, Poelzing S. The conduction velocity-potassium relationship in the heart is modulated by sodium and calcium. Pflugers Arch. 2021 Mar;473(3):557-571. PMID: 33660028.