Dissertation Defense: Pericyte and Endothelial Cell Responses within Murine Cerebral Capillaries After Blood Flow Cessation

Dissertation Defense: Pericyte and Endothelial Cell Responses within Murine Cerebral Capillaries After Blood Flow Cessation
Hanaa Abdelazim
Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Chappell Lab, Fralin Biomedical Research Institute at VTC
April 17, 2025, at 2 p.m.
4 Riverside, Room G101
More About the Candidate and Project
Education
Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate
Cairo University, M.D., Doctor of Medicine
Training
Graduate Research Assistant, Chappell Lab, Fralin Biomedical Research Institute at VTC
Mentors
John Chappell, Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC; Director, Translational Biology, Medicine, and Health graduate program, Virginia Tech
Committee Members
- Michael Fox, Ph.D., Dean, College of Natural Sciences, University of Massachusetts Amherst
- Jamie Smyth, Ph.D., Associate Professor, Fralin Biomedical Research Institute at VTC
- Samy Lamouille, Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC
Abdelazim, Hanaa, Mayd Alsalman, John C. Chappell. 2025. “Pericyte and Endothelial Cell Responses within Murine Cerebral Capillaries After Blood Flow Cessation.” Under preparation
Abdelazim, Hanaa, Audra Barnes, James Stupin, Ranah Hasson, Samy Lamouille, and John C. Chappell. 2024. “Optimized Enrichment of Murine Blood-Brain Barrier Vessels with a Critical Focus on Network Hierarchy in Post-Collection.” Under peer review
Payne, Laura Beth, Hanaa Abdelazim, Maruf Hoque, Audra Barnes, Zuzana Mironovova, Caroline E. Willi, Jordan Darden, Clifton Houk, Meghan W. Sedovy, Scott R. Johnstone, and John C. Chappell. 2023. “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, Vol. 13, Page 711 13(4):711. doi: 10.3390/BIOM13040711.
Willi, Caroline E., Hanaa Abdelazim, and John C. Chappell. 2022. “Evaluating Cell Viability, Capillary Perfusion, and Collateral Tortuosity in an Ex Vivo Mouse Intestine Fluidics Model.” Frontiers in Bioengineering and Biotechnology 10. doi: 10.3389/fbioe.2022.1008481.
Abdelazim, Hanaa, Laura Beth Payne, Kyle Nolan, Karan Paralkar, Vanessa Bradley, Ronak Kanodia, Rosalie Gude, Rachael Ward, Aboozar Monavarfeshani, Michael A. Fox, and John C. Chappell. 2022. “Pericyte Heterogeneity Identified by 3D Ultrastructural Analysis of the Microvessel Wall ” Frontiers in Physiology 13.
Hoque, Maruf M., Hanaa Abdelazim, Clifton Jenkins-Houk, Dawn Wright, Biraj M. Patel, and John C. Chappell. 2021. “The Cerebral Microvasculature: Basic and Clinical Perspectives on Stroke and Glioma.” Microcirculation 28(3): e12671. doi: 10.1111/MICC.12671.
- Student of the Year - TBMH Program (Science category) 2024
- James Carter Memorial Award for graduate students in translational neuroscience research 2024
- NIH-F31 Predoctoral Fellowship (NIH_F31HL168946): The Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship 2023
- Leadership Certificate - TBMH Program 2023
About this Dissertation
The microcirculation—an intricate network of the smallest blood vessels—is essential for delivering oxygen and nutrients to tissues while removing waste. Capillaries play a particularly important role in this exchange. A key cellular component of these microvessels are pericytes, a specialized cell that supports vessel stability and function. This dissertation focused on the exchange between pericytes, the endothelial cells that line all microvessels, and the extracellular matrix (ECM) providing a structural framework. Proper regulation of these constituents is critical for maintaining vessel integrity. In the brain, for instance, they form and stabilize the blood-brain barrier (BBB), which protects the brain from harmful substances while allowing adequate exchange. Here, Abdelazim, mentored by John Chappell, specifically investigated how blood flow impacts the BBB using an experimental model that mimics the brain microenvironment outside the body. This model allowed observation of pericyte behaviors after the loss of blood flow. The findings suggest that pericytes actively reshape the capillary wall during no-flow, coinciding with vascular inflammation and structural remodeling. Notably, rather than destabilizing, the BBB appeared to reorganize itself in response to pericyte constriction. A subset of capillaries narrowed due to the release of Endothelin-1 (ET-1), which likely induced pericyte contractility. Blocking ET-1 prevented key structural changes within endothelial cells, suggesting that ET-1 may play a role in capillary adaptions to blood flow perturbations. Thus, blood flow dynamics likely contribute to vascular dysfunction in unique ways that could have important implications for promoting brain health. By identifying how pericytes regulate vessel function and responses to blood flow changes, Abdelazim and the Chappell Lab have gained valuable insight into the risks associated with neurological disorders such as stroke and neurodegeneration. This knowledge may inspire new clinical therapies and ultimately shape strategies to safeguard brain health.