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Thesis Defense: PIntratumoral Heterogeneity in Interstitial Fluid Flow-Driven Glioblastoma Invasion.

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Nicole DeFoor

Thesis Defense: Intratumoral Heterogeneity in Interstitial Fluid Flow-Driven Glioblastoma Invasion.

Nicole DeFoor

Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Munson Lab, Fralin Biomedical Research Institute at VTC
May 5, 2026, at 9 a.m.
4 Riverside Circle, Room G101 A/B

 

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About this Thesis

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by extensive intratumoral heterogeneity and diffuse invasion into surrounding tissue, contributing to poor patient outcomes and frequent recurrence. Interstitial fluid flow (IFF) has emerged as a potential driver of GBM invasion through mechanisms such as autologous chemotaxis mediated by the CXCL12/CXCR4 signaling axis. However, the extent to which heterogeneous tumor subpopulations differentially respond to IFF remains unclear. Here, patient-derived GBM cells were clonally expanded from distinct subcolonies and evaluated for invasion in response to flow using xenograft mouse models. Tumor growth, invasion, fluid flow dynamics, and CXCR4 expression were assessed through MRI-based modeling and fluorescent imaging. Subcolonies exhibited distinct phenotypes, with subcolony 1 (SC1) and subcolony 3 (SC3) forming larger tumors with higher flow velocities, while subcolony 4 (SC4) formed smaller, more diffuse tumors with increased relative invasion. In combination tumors, dominant subcolonies dictated overall tumor behaviors, though individual subpopulations retained their invasive characteristics. Interestingly, invasion correlated with high-flow regions in SC1 and SC3, whereas SC4 demonstrated increased invasion in lower-flow environments. Despite these differences, all subcolonies showed a positive correlation between active CXCR4 and fluid flow in peritumoral regions. SC4 displayed elevated active cXCR4 despite lower total CXCR4 expression, suggesting enhanced sensitivity to chemokine gradients. These findings support a model in which IFF promotes GBM invasion through CXCL12/CXCR4-mediated autologous chemotaxis, regulated by intratumoral heterogeneity. Targeting this pathway may provide a strategy to limit invasion and reduce recurrence in GBM.

More About the Candidate and Project

Training

Graduate Research Assistant, Munson Lab

Education

Virginia Tech, B.S., Experimental Neuroscience

Mentor

  • Jenny M. Munson, Ph.D., Professor, Fralin Biomedical Research Institute at VTC; Director, Cancer Research Center - Roanoke; Professor, Department of Biomedical Engineering
     

Committee Members

Publications

  • Paul, S., Tomsick, P. L., Milner, J. P., Biswas, S. R., Brindley, S., DeFoor, N., Zavar, L., Wright, G., Soto, Y., Pickrell, A. M. (Apr 2026). "Disrupted autophagy overactivates TBK1 and results in mitotic defects promoting chromosomal instability." Autophagy 22(4):795-808. doi: 10.1080/15548627.2026.2617844.


  • Biswas, S. R., Tomsick, P. L., Kelly, C., Lester, B. A., Milner, J. P., Henry, S. N., Soto, S., Brindley, S., DeFoor, N., Morton, P. D., Pickrell, A. M. (Feb 2026). "Impaired Complex I dysregulates neural/glial precursors and corpus callosum development revealing postnatal defects in Leigh syndrome mice." EMBO Molecular Medicine 18(2):677-701. doi: 10.1038/s44321-025-00367-4.


  • Fritsch, L. E., Kelly, C., Leonard, J., de Jager, C., Wei, X., Brindley, S., Harris, E. A. M., Kaloss, A., DeFoor, N., Paul, S., O’Malley, H., Ju, J., Olsen, M. L., Theus, M. H., Pickrell, A. M. (Feb 2024). “STING-dependent signaling in microglia or peripheral immune cells orchestrates the early inflammatory response and influences brain injury outcome.” Journal of Neuroscience. e0191232024. DOI: https://doi.org/10.1523/JNEUROSCI.0191-23.2024


  • Paul, S., Sarraf, S. A., Nam, K. H., Zavar, L., DeFoor, N., Biswas, S. R., Fritsch, L. E., Yaron, T. M., Johnson, J. L., Huntsman E. M., Cantley, L. C., Ordureau, A., Pickrell, A. (Dec 2023). “NAK associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis.” Journal of Cell Biology 223(2). DOI: https://doi.org/10.1083/jcb.202303082.


  • DeFoor, N., Paul, S. Li, S., Basso, E. K. G., Stevenson, V., Browning, J. L., Prater, A. K., Brindley, S., Tao, G., Pickrell, A. M. (Sept 2023). “Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylation.” Scientific Reports 13(15339). DOI: https://doi.org/10.1038/s41598-023-42704-y.
  • 2025 TBMH Student of the Year for the community pillar
  • 2025 recipiant of the Zeta Beta Tau Graduate Fellowship
  • Virginia Summer Governor's School for Medicine - Volunteered to help develop the capstone project presented by students at the end of the summer. 2025
  • Virginia Summer Governor's School for Medicine - Presented to students on wet lab techniques and practices. 2024