Natalia Sutherland, a fourth-year student at the Virginia Tech Carilion School of Medicine (VTCSOM), has spent three years searching for a way to increase the effectiveness of treatment for the most common and aggressive form of primary brain cancer in adults: glioblastoma multiforme.

Working in the lab of Samy Lamouille, assistant professor at the Fralin Biomedical Research Institute at VTC, she has uncovered novel molecular mechanisms that could participate in glioblastoma progression, therefore holding promise for new treatments against this devastating disease.

Glioblastomas are extremely resistant to treatment. To date, the main regimen for treating these tumors is a chemotherapeutic agent called temozolomide, which can extend a person’s lifespan by only a few months. Sutherland’s research has centered on glioblastoma stem cells, a population of cancer cells originating in glioblastomas that are capable of both replicating and differentiating themselves.

“My role was to understand how glioblastoma stem cells differentiate into cancer cells that are more susceptible to traditional therapies like temozolomide,” she said.

In order to do this, Sutherland needed to determine how connexin 43, a protein that aids communication between cells, fit into the equation. She first observed differences in connexin 43 expression and localization in glioblastoma stem cells compared to differentiated cancer cells.

Sutherland also identified the regulation of connexin 43 expression and localization in glioblastoma stem cells to be dependent on a signaling molecule involved in neurodevelopment.

“We speculated that the way this signaling molecule regulates connexin 43 is through the Wnt/beta-catenin signaling pathway,” she said.

The Wnt/beta-catenin pathway has been found to be involved in glioblastoma stem cell maintenance, but this signaling crosstalk with connexin 43 had not been identified before in glioblastoma stem cells.

“Glioblastoma stem cells are incredibly complex,” she said. “These cells are also very different between patients, which makes them difficult to study. We’ve identified novel mechanisms that could modulate connexin 43 functions during glioblastoma stem cell differentiation. Now we need to determine whether interfering with these pathways could increase sensitivity to temozolomide or help develop new treatments to target glioblastoma stem cells.”

Graduating in May, Sutherland hopes another student or member of Lamouille’s research team at the Fralin Biomedical Research Institute will continue with the next steps in this intricate piece of biomedical research. She’s hoping her research will add to the body of knowledge for other researchers looking at better ways to treat brain cancer.

“This disease is devastating to patients and their families,” she said. “While there have been important discoveries made, we still have a lot of questions to ask and to answer before developing new technologies and treatments.”

Sutherland credits Lamouille, who is also an assistant professor in the VTCSOM Department of Basic Science Education and in the College of Science's Department of Biological Sciences, with supporting her and keeping her focused on this complex project.

“Dr. Lamouille has been instrumental in my medical school career,” she said. “He’s been incredibly supportive and a wonderful research mentor who is really excited about my research.”

After graduation in May, Sutherland will pursue a residency in internal medicine and plans to keep research a large part of her practice as a physician.

“Through consistent dedication and time spent on her research project, Natalia has made significant discoveries in the field,” Lamouille said. “She is truly a talented and creative researcher, and I look forward to following her career as she is on a clear trajectory to become a top physician scientist and leader in the future.”

VTCSOM has a rigorous research curriculum that helps prepare physician thought leaders as part of its mission. All students are expected to conduct an original, hypothesis-driven research project longitudinally throughout the course of their medical school curriculum before graduation. This requirement ensures that students are immersed in the language, culture, and practice of original research.

“Research has helped me develop so many skills,” Sutherland said. “It’s shown me how to dive through the literature, how to ask important questions, how to look for gaps in the knowledge. So much of our careers as physicians will be focused on evidence-based medicine. We will need to understand how studies are designed and implement that evidence into our everyday practices.”

Sutherland will give a presentation on her project at VTCSOM’s annual Medical Student Research Symposium, which is from noon to 5:45 p.m. on Friday, March 25. Seven of the students in the class selected to receive Letters of Distinction for their project, including Sutherland, will give oral presentations. All of the members of the Class of 2022 will provide poster presentations on their projects.

Learn how to attend the symposium.

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