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Dissertation Defense: Targeting S1PR3 to mitigate flow-enhanced invasion in the glioblastoma tumor microenvironment

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Samantha Howerton

Dissertation Defense: Targeting S1PR3 to mitigate flow-enhanced invasion in the glioblastoma tumor microenvironment

Samantha Howerton

Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Munson Lab, Fralin Biomedical Research Institute at VTC
December 4, 2025, at 12 p.m.
Riverside 4, Room G101 A/B
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More About the Candidate and Project

Education

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

Concord University, B.S., Molecular Biological 

Training

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

Mentors

Jennifer Munson, Ph.D., Professor, Fralin Biomedical Research Institute at VTC; Director, Cancer Research Center — Roanoke; Professor, Department of Biomedical Engineering and Mechanics, College of Engineering

Committee Members

  • Michelle Olsen, Ph.D., Director, School of Neuroscience; Professor, School of Neuroscience
  • Benjamin Purow M.D., Professor, UVA Health Neurology; Clinical Physician, UVA Health Neurology
  • Samy Lamouille Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC, Research Assistant Professor, Department of Biological Sciences, College of Science, Assistant Professor, Department of Basic Science Education, School of Medicine

Publications

  • Howerton, S.*, Geraldo Mendes, G.*, Munson, J. The immune system and its role in the nervous system. in Handbook of Neural Engineering 149–177 (Academic Press, 2025). doi:10.1016/B978-0-323-95730-4.00014-7.
  • Howerton, S., Liang, Y., Hammel, J., Purow, B. & Munson, J. A Photopolymerizable Hyaluronic Acid-Collagen Model of the Invasive Glioma Microenvironment with Interstitial Flow. J Vis Exp https://doi.org/10.3791/66604 (2024) doi:10.3791/66604.
  • Cornelison, R.C.4*, Howerton, S.*, Tate, K., Stine C., Petrosky, A., Kingsmore, K.M., Michelhaugh, S., Cunningham, J., Degen, K., Hoggarth, A., Carman-Esparza ,C., Jin, P., Wang, M., O’Brien, C., Zhao, A., Pfaff, B., Purow, B.W., Mandell, J., Olsen, M., Kimbrough, I., Witcher, M., Munson, J. S1PR3 mediates glial stimulated tumor invasion in response to interstitial fluid flow. In submission.


*Equal Contributions

  • Howerton, S.*, Cornelison, R.C., Stine, C., Jin, P., Carman-Esparza, C., Cunningham, J., Michelhaugh, S., Wang, M., O'Brien, C., Roberts, M., Munson, J. Influence of the tumor microenvironment on S1PR3-driven, flow-enhanced invasion. Cancer Research Center Symposium (Fralin Biomedical Research Institute), 2025 (Poster), Roanoke, VA
  • Howerton, S.*, Cornelison, R.C., Stine, C., Cunningham, J., Carman-Esparza C., O’Brien C., Roberts, M., Munson, J. Leveraging tumor microenvironment models to investigate the role of S1PR3 in mediating flow-enhanced glioma invasion. Gordon Research Conference: Physical Science of Cancer, 2025 (Poster), Pomona, CA
  • Howerton, S.*, Cornelison, R.C., Carman-Esparza C., Munson, J. Targeting S1PR3-driven, interstitial fluid flow-enhanced invasion in glioblastoma with a patient-specific, tumor microenvironment approach. Commonwealth of Virginia Cancer Research Conference, 2023 (Oral), Charlottesville, VA
  • Howerton, S.*, Carman-Esparza, C., Munson, J. Predicting efficacy of S1PR3-targeted therapy in glioma across patient-based models: the potential role of glia. Translational Biology, Medicine, and Health Annual Symposium, 2023 (Poster), Roanoke, VA
  • Kremer, S.*, John, R., Jin, P., Michelhaugh, S., Cunningham, J., Howerton, S., Eze, A., Nazarian J., Munson, J. Characterization of the tumor microenvironment in diffuse midline gliomas (DMG) for 3D in vitro model building. Society for Neuro-Oncology Annual Meeting, 2023 (Poster), Vancouver, Canada
  • Howerton S.*, Michelhaugh S., Munson, J. Targeting interstitial fluid flow enhanced invasion across glioma models via the lipid receptor S1PR3. Translational Biology, Medicine, and Health Annual Symposium, 2023 (Poster), Roanoke, VA
  • Howerton, S.*, Munson, J. S1PR3 is differentially expressed at the tumor invasive front across patients with glioblastoma. Precision Neuroscience Conference, 2022 (Poster), Roanoke, VA
  • Howerton S.*, Finkielstein, C. Mutant PER2/p53 interactions inhibit DNA damage response. Translational Biology, Medicine, and Health Rotation Presentations, 2021 (Oral), Roanoke, VA
  • Howerton, S.*, Tate, K., Munson, J. Neural stem cells modulate glioma stem cell invasion during fluid flow. Translational Biology, Medicine, and Health Rotation Presentations, 2021 (Poster), Roanoke, VA

*Presenter

  • Jeanine L. Matte Fellowship (Fralin Biomedical Research Institute), June 2024
  • Member, Cancer Research Center Social Planning Committee, Fralin Biomedical Research Institute (fall 2024-spring 2025)
  • Volunteer, Hokie for a Day, Virginia Tech, Blacksburg, VA (spring 2025)
  • Judge, Roanoke County Science Fair, Northside High School, Roanoke, VA (spring 2024)
  • Guest Speaker, Roanoke Valley Governor’s School for Science and Technology, Roanoke, VA (spring 2023)
  • Judge, Project Forum, Roanoke Valley Governor’s School for Science and Technology, Roanoke, VA (spring 2023)
  • Volunteer, Brain School, Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA (spring 2022)
  • Volunteer, VT Science Festival, Virginia Tech, Blacksburg, VA (fall 2021)

About this Dissertation

Glioblastoma is a devastating disease with few effective treatments, in part owed to the dynamic cellular and biophysical factors that influence tumor progression and therapy response. Emerging evidence has implicated pathological interstitial fluid flow, created by high intratumoral pressure relative to the healthy parenchyma, in enhancing cancer invasion. Multiple targetable molecular pathways have been identified that drive this response, but the specific pathways employed by invasive cells differs between patient glioma cell lines. To this end, we sought to identify additional therapeutic candidates mediating flow-enhanced invasion. Our previous work established a role for the G-protein coupled receptor S1PR3 in enhancing invasion under flow. Interestingly, we found this response to be mediated by the brain parenchymal cells, astrocytes and microglia. In this work, we demonstrate clinical relevance for S1PR3 as both a biomarker and therapeutic target with efficacy across a heterogeneous patient cohort. To inform therapeutic development, we investigate the intercellular mechanisms involved in S1PR3-driven invasion. We find that S1PR3 targeting significantly alters flow dynamics in vivo. We connect astrocytic S1PR3 to flow response, finding correlations with flow in both tumor-bearing and tumor-naïve settings, suggesting redundancy across neuropathologies. We build evidence that astrocytic S1P and S1PR3 mediates the response to fluid shear stress and we imply roles for S1P and flow-sensing. This work has exciting implications suggesting a dual role for S1PR3 in flow-regulation and flow-response, thus it may be a doubly effective target for minimizing flow-enhanced glioma invasion.