By Meghan Chua
When PhD candidate Michelle Pizzo joined the Pharmaceutical Sciences program, she didn’t know what, exactly, she would be researching.
Since then, she has made advancements in the field of pharmaceutical science and discovered a new direction she is excited to pursue.
Joining the Thorne lab in 2012, Pizzo came on board at a time when a new project was developing. Researchers already believed that the perivascular spaces – the tubular spaces around blood vessels – in the brain could take on waste clearance role, but the Thorne lab wanted to see if those routes could also be used to deliver drugs to the brain, Pizzo said.
Finding such a route could provide more treatment options for brain cancer, autoimmune disorders such as multiple sclerosis, and a large group of metabolic disorders. These diseases require treatment in the whole brain, rather than a specific site, making effective treatment a question of how to deliver drugs throughout the whole brain.
“The brain is a protected site, so just administering something into the blood is not going to get it there,” Pizzo explained. “You really need to bypass some of those barriers, and we think infusing directly into the fluid around the brain can help.”
Pizzo specializes in a technique called intrathecal administration, where drugs are injected into the cerebrospinal fluid that surrounds the brain and spinal cord, aimed at using the fluid as a means of transportation for treatment drugs. Because no one in the lab was actively working on the topic before Pizzo joined, she developed the project from its start. Designing the experiment was appealing, Pizzo said, and became even more interesting once the results started coming in.
“It was really exciting to, especially, see the differences between different types of molecules that you administer,” she said, adding that larger molecules tend to have a harder time getting into the brain than smaller molecules.
In a key discovery for the field, Pizzo found that by accessing perivascular spaces, larger molecules – such as antibodies and other large-molecule protein therapeutics – could travel around the brain just as quickly as smaller molecules. The paper was published in The Journal of Physiology in October.
“I and many others believe that Michelle’s work will be quite impactful over time, influencing the field for years to come,” said Robert Thorne, an assistant professor in the School of Pharmacy.
The next step was to look at how those same processes could be affected by diseases themselves.
“Normally we’re treating someone who already has a diseased brain and we’re trying to fight that,” Pizzo said. “So, how is the disease affecting the anatomy and the structure of the brain in a way that is going to help or hinder delivery?”
To answer that question, Pizzo looked at a brain cancer model in rats, collaborating with UW–Madison neurosurgery professor John Kuo. The study found that brain tumors do, indeed, hinder drug delivery.
The way that other, different diseases affect drug delivery in the brain is a future direction for Pizzo. She hopes to expand her focus on the brain to include cancer expertise, and make brain cancer and drug delivery the next step in her research career.
In addition to research, Pizzo became involved in outreach activities through the Neuroscience Training Program, Wisconsin Science Festival, Science Expeditions, and Expanding Your Horizons, a program for girls to gain interest in STEM careers. Pizzo said she sees outreach as a good way to encourage scientific curiosity among young future scientists and their parents alike.
“It’s nice to interact with not only the children but also their parents,” she said. “So many of the parents never had these opportunities when they were a kid, so it’s really fascinating for them to be involved.”
Pizzo, who defended her dissertation Thursday, was among the roughly 900 graduate students who earned a PhD, MFA or medical professional degree at spring commencement Friday.
Looking back on her time as a research assistant at UW–Madison, Pizzo said she would not have been afraid to ask others with more lab experience for help, especially at the start of her research career.
She also highlighted the collaborations she found at UW–Madison.
“One thing that I always think of when I think of UW is the collaborate environment. Everyone in our department and everyone I’ve met in the university is incredibly supportive of helping you in your work, in your project, but also helping advance your career.”