About nine years ago, Jennifer Munson jotted down a question in her notes. She wondered how chemotherapy affects the brain. Around that time, scientists were beginning to uncover new information about a network of vessels lining the brain’s outermost layer. These vessels play a critical role: they drain blood, waste product and other fluids from the brain, helping maintain balance in the central nervous system.
Now, about a decade later, Munson’s lab at the Fralin Biomedical Research Institute at Virginia Tech uncovered how chemotherapy can damage that same drainage system. This may help explain why so many chemotherapy patients experience lasting cognitive problems known as “chemo brain.” Her findings not only shed light on a long-standing medical problem but also position Southwest Virginia as a growing center for biomedical research at the intersection of engineering and neuroscience.
In 2018, a study linked this waste-disposal system to Alzheimer’s disease, according to a study published in Nature. Researchers have implicated these vessels in several other neurological disorders, Munson said.
Since her lab is focused on fluid flow and drainage, Munson wanted to know whether these vessels might also contribute to the cognitive effects of chemotherapy. Commonly referred to as “chemo-brain,” about 3 in 4 cancer patients experience brain fog and memory and word recall problems after receiving the treatment. And more than half of all people diagnosed with cancer receive chemotherapy, according to the Virginia Cancer Institute. While it’s an effective therapy, it can be hard on the body.
The short answer to Munson’s question, nearly a decade later, is yes. Her team found that chemotherapy damages the brain’s drainage vessels, disrupting the system and contributing to symptoms of chemo brain.
“Inherently, that’s really hard to study,” Munson said. “When you get cancer treatment, it’s usually treating the whole body. So it’s getting into the brain, but it’s also getting into these vessels. And it’s getting into everything in between. It can have effects on all of those tissues differently.”
Building models to study the brain’s drainage system
Because no existing model could capture this process, Munson’s team of engineers built three experimental models from the ground up. One involved tissues taken from mice and kept in culture, one in live mice treated with chemotherapy and one in the lab with human cells.
This work resulted in the first lab-grown human tissue system that replicates the lymphatic tissue surrounding the brain. The model could eventually support therapeutic testing, patient analysis and disease-specific studies.
The team looked at two common chemotherapy drugs: docetaxel and carboplatin. Both damaged the brain’s vessels, but docetaxel caused greater harm.
Munson said the finding surprised her. In earlier breast cancer research, her lab had observed different effects from docetaxel.
“These lymphatics that drain the brain seem to be unique, like they do seem to respond to things differently than lymphatics do around the body,” Munson said. “There is a need for making sure we’re building models that are tissue specific. That was really interesting. It complicates things, obviously, for the whole field of science but I was happy that we were able to see those differences across all our models.”
Now that researchers know how chemotherapy affects this system, Munson sees hope for treatments for the cognitive deficits that sometimes follow chemotherapy. Medications and other therapies already exist to support the lymphatic system, which could one day help reduce chemo-brain.
Her lab is now using this model to study Alzheimer’s disease, and she hopes that others will use it to study other diseases.
Models like these help researchers see how different bodily systems interact when a treatment is applied, Munson said. Her lab is also looking at how multiple tissues respond and communicate in the body.
A research hub in Southwest Virginia
Before joining Virginia Tech, Munson lived and worked in larger cities. She moved to Roanoke in 2020 to join the Fralin Biomedical Research Institute, part of Virginia Tech’s growing health sciences and engineering campus.
The proximity of Virginia Tech, a hub for engineering, and the research center in Roanoke has created a strong foundation for new and interesting science, Munson said.
Living and working in a more rural setting also allows her to connect more closely with the community. She often hears from residents in surrounding areas who have questions about the work she’s doing.
“I think that’s a really unique part about FBRI and that’s very motivating. It’s very motivating for the students and the researchers. And I hope it’s motivating for the community to continue to enjoy and stay in touch with what we’re working on,” Munson said.
Funding and the challenges of scientific risk
The National Institutes of Health played a key role in supporting Munson’s research. The National Cancer Institute, part of NIH, funded her lab’s early work on fluid flow. Later, as NIH expanded its focus on Alzheimer’s and cognitive decline, Munson received grants from the National Institute on Aging.
They sought out researchers with interesting ideas who weren’t immersed in research related to cognitive decline. This funding from NIH allowed her team to take a leap into an untested area of science.
The NIH, which funds the majority of biomedical research in the United States, is facing potentially unprecedented reductions in its budget and changes to how it reimburses research institutions, according to the American Medical Association.
The current unpredictability in funding at the federal level for NIH makes it difficult for researchers to take risks, Munson said.
“This project was definitely a risky project, and it took a while because of that. It’s not a connection that’s been made before, and I’m not squarely in this research area,” Muson said. “It was a risk to do that and make these big leaps without some stability in place.”
But the risk paid off. Her team’s work now offers a new window into how chemotherapy affects the brain and a path forward for treating the cognitive side effects that so many cancer survivors face.