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Dissertation Defense: A Translational Approach to Understanding Cellular Responses to Vascular Injury

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Meghan Sedovy

Dissertation Defense: A Translational Approach to Understanding Cellular Responses to Vascular Injury

Meghan Sedovy

Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Johnstone Lab, Fralin Biomedical Research Institute at VTC
April 8, 2025, at 9 a.m.
4 Riverside, Room G101
Visit the Johnstone Lab
Watch via Zoom

More About the Candidate and Project

Education

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

Virginia Tech, B.S., Clinical Neuroscience

Training

Graduate Research Assistant, Johnstone Lab, Fralin Biomedical Research Institute at VTC

Mentors

Scott Johnstone, Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC

Committee Members

  • Samy Lamouille, Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC
  • Robert Gourdie, Ph.D., Professor, Director, Center for Vascular and Heart Research, Fralin Biomedical Research Institute at VTC
  • Brant Isakson, Ph.D., Professor, Molecular Physiology and Biological Physics, University of Virginia School of Medicine
  • Liwu Li, Ph.D., Professor, Biological Sciences, Virginia Tech

Publications

Sedovy MW, Leng X, Iqbal F, et al. Preserving Endothelial Integrity in Human Saphenous Veins during Preparation for Coronary Bypass Surgery. J Vasc Res. 2024;61(2):68-76. doi:10.1159/000535843

Sedovy MW, Leng X, Leaf MR, et al. Connexin 43 across the Vasculature: Gap Junctions and Beyond [published online ahead of print, 2022 Dec 13]. J Vasc Res. 2022;1-13. doi:10.1159/000527469

Sedovy MW, Renton MC, Roberts K, Leng X, Dennison CL, Leaf MR, et al. Injury Induced Connexin 43 Expression Regulates Endothelial Wound Healing. bioRxiv. 2025:2025.02.24.639946. (preprint)

Payne LB, Abdelazim H, Hoque M, Barnes A, Mironovova Z, Willi CE, Darden J, Houk C, Sedovy MW, Johnstone SR, Chappell JC. A Soluble Platelet-Derived Growth Factor Receptor-β Originates via Pre-mRNA Splicing in the Healthy Brain and Is Upregulated during Hypoxia and Aging. Biomolecules. 2023 Apr 21;13(4):711. doi: 10.3390/biom13040711. PMID: 37189457; PMCID: PMC10136073.

King DR, Mezache L, Sedovy MW, Radwański PB, Johnstone SR, Veeraraghavan R. Cell-Cell Communication in the Vascular Endothelium. In: Parinandi, N.L., Hund, T.J. (eds) Cardiovascular Signaling in Health and Disease (2022). Springer, Cham. doi.org/10.1007/978-3-031-08309-9_15

King DR, Sedovy MW, Eaton X, et al. Cell-To-Cell Communication in the Resistance Vasculature. Compr Physiol. 2022;12(4):3833-3867. Published 2022 Aug 12. doi:10.1002/cphy.c210040

King DR, Sedovy MW, Leng X, Xue J, Lamouille S, Koval M, Isakson BE, Johnstone SR. Mechanisms of Connexin Regulating Peptides. International Journal of Molecular Sciences. 2021; 22(19):10186.

Posters

Meghan W. Sedovy, Mark Renton, Xinyan Eaton, Farwah Iqbal, Arya Malek, Kailynn Roberts, Scott R. Johnstone. Endothelial injury induced connexin 43 expression regulates vascular healing. Presented at International Gap Junction Conference 2024

Meghan W. Sedovy, Xinyan Eaton, Farwah Iqbal, Arya Malek, Kailynn Roberts, Scott R. Johnstone. Injury induced Connexin 43 expression plays a role in vascular endothelial wound healing. Presented at Vascular Discovery 2023: From Genes to Medicine

Sedovy MW, King DR, Eaton X, Joshi RC, Baker JW, Joseph M, Smyth JW, Isakson BE, Johnstone SR. Connexin 43 as a Regulator of Proliferation and Neointimal Formation in Human Vascular Tissue. Presented at NAVBO Vascular Biology 2021

Talks

  • 07/28/2024 International Gap Junction Conference – “Macrophages initiate smooth muscle cell proliferation via gap junctions during neointima formation”
  • 11/28/2023 Fall 2023 Research in Progress Symposium – “The role of Connexin 43 in vascular endothelial repair”
  • 06/08/2023 University of Virginia Endothelial Interest Group – “The role of endothelial connexins in vascular repair”
  • 02/04/2023 Department of Biological Sciences Research Day - “The role of endothelial connexins in vascular repair”
  • 10/27/2022 Fall 2022 Research in Progress Symposium - “The role of endothelial connexins in vascular repair”
  • 07/18/2022 International Gap Junction Conference - “Connexin 43 as a regulator of proliferation and neointimal formation in human tissue”
  • 02/05/2022 Department of Biological Sciences Research Day - “Connexin 43 as a regulator of proliferation and neointimal formation in human tissue”
  • 12/14/2021 Fall 2021 Research in Progress Symposium - “Connexin 43 as a regulator of proliferation and neointimal formation in human tissue”
  • 12/09/2021 Invited talk for NAVBO Vascular Injury and Repair InFocus session - “Connexin 43 as a regulator of proliferation and neointimal formation in human tissue”

Fellowships and Grants

  • 03/2024 – 03/2025 Virginia Tech LAUNCH Proof Of Concept award 
  • 08/2023 – 01/2026 NIH F31 Predoctoral Fellow
  • 01/2023 – 08/2023 American Heart Association Predoctoral Fellow

Honors and Awards

  • 07/28/2024 1st place PhD student talk at the International Gap Junction Conference
  • 06/12/2024 2nd place poster award at the Fralin Biomedical Research Institute annual retreat
  • 11/05/2023 TBMH student of the year in science 
  • 07/08/2022 Virginia Tech Center for Vascular and Heart Research retreat 2022 2nd place poster award
  • 02/05/2022 1st place breakout session talk at Virginia Tech Department of Biological Sciences Research Day
  • 10/20/ 2021 NAVBO Vascular Biology 2021 Outstanding Poster Award
  • 13/05/2024 American Heart Association STEM Goes Red for Women event organizer and breakout session leader
  • 19/05/2023 American Heart Association STEM Goes Red for Women event organizer and volunteer mentor
  • 03/11/2023 Western Virginia Regional Science Fair judge
  • 03/20/2022` Western Virginia Regional Science Fair judge
  • 03/14/2022 Fralin Biomedical Research Institute “Brain School” volunteer 
  • 20/03/2021 Western Virginia Regional Science Fair judge

About this Dissertation

Appropriate control of cell proliferation and migration is essential for maintaining open arteries after vascular injury. Connexin 43 is a channel protein that facilitates cell to cell communication and regulates cell proliferation as well as migration, yet it’s role in vascular cell types is poorly understood. Here, Sedovy hypothesized that Cx43 and its functional regulation by kinases play a role in vascular cell injury response. To investigate this, Sedovy used human vascular tissue from coronary artery bypass grafts and mouse models of ligation induced vascular injury. First, she investigated vessels used for coronary artery bypass, finding damage to the vascular endothelium that could not be completely reversed by improved presurgical vessel storage methods. She developed a carotid artery ligation model of endothelial injury in mice, and found that Cx43 was expressed only in injured endothelial cells, where it promoted healing through control of proliferation and migration. Sedovy also identified Mitogen Activated Protein Kinase (MAPK) phosphorylation of Cx43 as the mechanistic event controlling Cx43 dependent endothelial wound healing. In vascular smooth muscle, MAPK dependent Cx43. phosphorylation drove excessive proliferation leading to neointima formation and vascular blockage. A Johnstone lab-developed peptide that targets this phosphorylation state prevents neointima formation in mouse and human tissues. These findings highlight a role for Cx43 phosphorylation by MAPK in vascular cell response to mechanical injury and identify Cx43 and a therapeutic target for preventing smooth muscle driven vascular disease.