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Katrina Colucci-Chang's Dissertation Defense (5/4/2022): The Relationship between Ephaptic Coupling and Excitability in Ventricular Myocardium

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Katrina Colucci-Chang

Dissertation Defense: The Relationship between Ephaptic Coupling and Excitability in Ventricular Myocardium

Katrina Colucci-Chang

Graduate Student, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences at Virginia Tech
Graduate Research Assistant, Poelzing Lab, Fralin Biomedical Research Institute at VTC
May 4, 2022 at 9:00 a.m.

About this Dissertation

The heart is a muscular organ that uses electrical impulses to function. The heart is made of cells called cardiomyocytes that allow for electrical signals to flow through the cells. Any loss of electrical coordination between cardiomyocytes can lead to irregular heartbeats, or worse sudden cardiac death. There are two ways to study electrical coordination: excitability – how easy it is to start electrical activity in tissue, and conduction – how quickly does the electrical signal travel through the tissue. Since the 1900s, researchers have stated that if excitability decreases conduction decreases. In other words, if more current is needed to start the heart (decreased excitability) then that electrical signal will travel slower through the tissue (decreased conduction speed) and the risk of sudden death increases. Within the last 20 years, our understanding of how conduction works has significantly changed, but our understanding of excitability has not. For example, electrical conduction was thought to travel through proteins called gap junctions, and if gap junctions uncoupled, conduction would decrease, and presumably so would excitability. However, loss of functional gap junctions is not always associated with slowed conduction. Therefore, a new mechanism of electrical conduction called ephaptic coupling was proposed. In short, ephaptic conduction can occur in a gap junction adjacent extracellular space rich in sodium channels necessary for conduction. Altering the intercellular separation within these nanodomains can preserve conduction even as gap junctional coupling is reduced. Importantly, these extracellular spaces are extremely narrow and relatively isolated from the bulk extracellular fluid where electrical stimulation by devices occurs. Therefore, the purpose of Katrina Colucci-Chang's project is to understand if the isolated nature of these extracellular spaces changes excitability, and to test if excitability still correlates with conduction when the size of that nanodomain is altered. Using mathematical and animal models, this dissertation demonstrates that excitability and conduction are not linearly related. In other words, these two important biophysical properties may depend on similar mechanisms, but their response to interventions are not similar.

More About the Candidate and Project

Education

Virginia Tech School of Biomedical Engineering and Sciences, Ph.D. Candidate

George Mason University, B.S., Bioengineering

Training

Graduate Research Assistant, Poelzing Lab and Center for Vascular and Heart Research

 

Mentor

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

Committee Members

  • Susan Campbell, Ph.D., Assistant Professor, Department of Animal and Poultry Sciences, College of Agriculture and Life Sciences, Virginia Tech
  • John Chappell, Ph.D., Associate Professor, Fralin Biomedical Research Institute at VTC
  • Robert Gourdie, Ph.D., Commonwealth Research Commercialization Fund Eminent Scholar in Heart Reparative Medicine Research and Director, Center for Vascular and Heart Research, Fralin Biomedical Research Institute at VTC
  • William Huckle, Ph.D., Associate Professor, Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine at Virginia Tech, and Associate Dean, Graduate School, Virginia Tech

Honors

  • SMART-DoD NAVY-NAVAIR Fellowship Recipient
  • VT-Initiative for Maximizing Student Development (IMSD) Member
  • GEM Consortium Associate Fellow

Presentations

Oral: 

Katrina Colucci-Chang, The Role of Perinexus on Cardiomyocyte Excitability, The GEM National Consortium 2020- (2nd place)

Colucci-Chang, K., Adams, W., Wu, X., Bhagia, S., Ragauskas, A. J., Hanlin, A., ... & Poelzing, S, Decreased Ephaptic Coupling Depresses Cardiac Excitability and Slows Conduction. Biophyisical Society 2022- February 19-23, 2022

Posters: 

Katrina Colucci-Chang, Gregory Hoeker Ph.D, Steve Poelzing Ph.D, Trace Metal Corrosion from Grounding Electrodes in Saline Solution Affecting Cardiac Electrophysiology,  dmvCAPS, (Best Graduate Posters)

Katrina Colucci-Chang, Elizabeth McNeil Ph.D, Pamela VandeVord Ph.D - Protocol Development to Measure the Concentration of Cell Free Nucleic Acid in Minipigs, October 2018 –, BMES 2018 Atlanta

Katrina Colucci-Chang, Xiaobo Wu, Grace Blair, Alicia Lozano, Alexandra Hanlon, and Steven Poelzing Perinexal Width Modulates Sodium Channel Recruitment During Extracellular Stimulation, AHA Scientific Session 2020- November 13-17, 2020

Publications

Colucci-Chang, K., Adams, W., Wu, X., Bhagia, S., Ragauskas, A. J., Hanlin, A., ... & Poelzing, S. (2022). Decreased ephaptic coupling depresses cardiac excitability and slows conduction. Biophysical Journal121(3), 13a.

Colucci Chang, Katrina, Xiaobo Wu, Grace Blair, Alicia Lozano, Alexandra Hanlon, and Steven Poelzing. "Perinexal Width Modulates Sodium Channel Recruitment During Extracellular Stimulation." Circulation 142, no. Suppl_3 (2020): A16722-A16722.

 

  • Graduate Representative, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences in Roanoke
  • Judge, Virginia State Science and Engineering Fair, 2018 – 2021
  • Judge, Western Virginia Regional Science Fair, 2018 – 2021
  • Judge, Roanoke Valley Governor’s School Project Forum, 2018 – 2021 
  • Judge, ABRCMPS Undergraduate Science Fair, 2021
  • Judge, Radford Science Fair/ Blue Ridge Highlands Regional Science Fair, 2018-2021
  • VALHEN-HCI, Motivational Speaker, Workshop Leader, 2015-Present