Virginia Tech® home

Randy Strauss's Dissertation Defense (9/13/2021): The Cx43 Carboxyl-Terminal Mimetic Peptide, αCT1, Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner

Insert your title here

Your Text Here
Randy Strauss
Dissertation Defense: The Cx43 Carboxyl-Terminal Mimetic Peptide, αCT1, Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner

Randy Strauss

Graduate Student, Virginia Tech Translational Biology, Medicine, and Health
Graduate Research Assistant, Gourdie Lab and the Center for Vascular and Heart Research, Fralin Biomedical Research Institute at VTC
Sept. 13, 2021 at 12:00 p.m.
Location:  Room R3012, 2 Riverside Circle
 
Visit the Gourdie Lab

About this Dissertation

The Cx43 CT mimetic peptide, αCT1, originally designed to bind to ZO1 and thereby inhibit Cx43/ZO1 interaction, was used as a tool to probe the role of Cx43/ZO1 association in regulation of epithelial/endothelial barrier function. Using both in vitro and ex vivo methods of barrier function measurement, including Electric Cell-Substrate Impedance Sensing(ECIS), a TRITC-dextran transwell permeability assay, and a FITC-dextran cardiovascular leakage protocol involving Langendorff-perfused mouse hearts, αCT1 was found to protect the endothelium from thrombin-induced breakdown in cell-cell contacts. Barrier protection was accompanied by significant remodeling of the F-actin cytoskeleton, characterized by a redistribution of F-actin away from the cytoplasmic and nuclear regions of the cell, towards the endothelial cell periphery, in association with alterations in cellular orientation distribution. In line with observations of increased cortical F-actin, αCT1 upregulated cell-cell border localization of endothelial VE-cadherin, the Tight Junction protein Zonula Occludens 1 (ZO1) , and the Gap Junction Protein (GJ) Connexin43 (Cx43). A ZO1-binding-incompetent variant of αCT1, αCT1-I, indicated that these effects on barrier function and barrier-associated proteins, were likely associated with Cx43 CT sequences retaining ability to interact with ZO1. These results implicate the Cx43 CT and its interaction with ZO1, in the regulation of endothelial barrier function, while revealing the therapeutic potential of αCT1 in the treatment of vascular edema.

Strauss abstract model

More About the Candidate and Project

Education

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

University of Delaware, B.S., Neuroscience, B.A., Psychology

Training

Graduate Research Assistant, Gourdie Lab and the Center for Vascular and Heart Research, Fralin Biomedical Research Institute at VTC

 

Mentor

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

Committee

  • Michael Koval, Ph.D., Professor, Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine
  • James Smyth, Ph.D., Associate Professor, Fralin Biomedical Research Institute at VTC
  • John Chappell, Ph.D., Associate Professor, Fralin Biomedical Research Institute at VTC
  • Michael Fox , Ph.D., Professor, Fralin Biomedical Research Institute at VTC, and director, School of Neuroscience, College of Science, Virginia Tech

Honors

  • Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31), April 2019
  • Young Trainee Award, International Gap Junction Conference , July 2019
  • Fralin Biomedical Research Institute Lab Olympics Champion, 2018
  • Travel Fund Program Award, Virginia Tech Graduate School, July 2017
  • First Place Team, Shark Tank Competition, 2016

Publications

Strauss RE, Mezache L, Veeraraghavan R, Gourdie RG. The Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner. Biomolecules. 2021; 11(8):1192.

Strauss RE, Gourdie RG. Cx43 and the Actin Cytoskeleton: Novel Roles and Implications for Cell-Cell Junction-Based Barrier Function Regulation. Biomolecules. 2020 Dec 10;10(12):1656.

 Jiang JB, Strauss R, Luo XQ, Nie C, Wang YL, Zhang JW, Zhang ZW. Anaesthesia modalities during laser photocoagulation for retinopathy of prematurity: a retrospective, longitudinal study. BMJ Open. 2017 Jan 24;7(1):e013344.

Obert E, Strauss R, Brandon C, Grek C, Ghatnekar G, Gourdie R, Rohrer B. Targeting the tight junction protein, zonula occludens-1, with the connexin43 mimetic peptide, alphaCT1, reduces VEGF-dependent RPE pathophysiology. J Mol Med (Berl). 2017 May;95(5):535-552.

Strauss R, Gourdie RG. The Connexin 43 Carboxyl-Terminus affects Tight Junction Function Via ZO-1 Targeting . Proceedings of the International Gap Junction Conference. 2017 July 29-Aug 2nd. Glasgow, Scotland; 2017 Abstract PS2.74

Benjamin P. Heithoff, Jane Jourdan, Randy Strauss, Robert G. Gourdie, Stefanie Robel. “Glial Fibrillary Acidic Protein (GFAP) may be an essential player in keeping the aging blood-brain barrier healthy”; Poster presented at Glia in Health and Disease Conference 2018, Cold Spring Harbor, NY

Presentations

International Gap Junction Conference, Victoria Canada, 2019 (Oral Presentation)

Pannexin Conference, University of Virginia, 2019 (Oral Presentation)

International Gap Junction Conference, Victoria Canada, 2019 (Poster)

  • Graduate Student Ambassador, Virginia Tech, 2017
  • Roanoke River Greenway Cleanup, 2017

You May Also Be Interested In...