One student's journey from volunteer in the lab to independent undergraduate researcher
For Ryan Clark (BME ’20), it is an extraordinary opportunity. As a Beckman Scholar, this University of Virginia fourth-year student has funding to conduct a 15-month, independent research project that could lead to better treatment for triple negative breast cancer, a form of breast cancer that is highly metastatic and therefore difficult to treat. “I am really excited and fortunate to be working on a project I have designed by myself from the ground up,” Clark said. Clark is working in Professor of Biomedical Engineering Richard Price’s lab, where he is investigating the potential of focused ultrasound to stimulate an immune response to this form of cancer.
“This is a highly prestigious award, both for Ryan and for the University,” Price, the director of UVA’s Beckman Scholars Program, said. UVA is among a small group of universities nationwide funded by the Arnold and Mabel Beckman Foundation to award Beckman Scholarships. In 2019, the foundation awarded $1.7 million through these universities to 68 undergraduate scholars.
Help Getting Started
Clark’s path to the Beckman reflects both his early passion for research, particularly in immunology, and the mentoring he received at UVA, which helped him grow and develop as a researcher. Having participated in several year-long research projects in high school, he arrived at UVA looking to find a home in a research lab. By the end of his first year, he was firmly ensconced in the Price Lab, where Natasha Sheybani, now a senior graduate student, took him under her wing.
“More than anything else, I look for students with grit, enthusiasm and an eagerness to get involved,” Sheybani said. “This is important because the initial learning curve is steep and much of what students begin with is not that exciting.”
Sheybani introduced Clark to the different ways focused ultrasound might be used to treat disease and familiarized him with projects underway in the Price Lab. In focused ultrasound, a beam of ultrasound waves is focused on a point, causing a range of effects in the target tissue from vibration to heating. She suggested readings that shed light on the scientific issues and technical processes he was observing in the lab, which led him to look at research papers in a new light.
“Natasha helped me see that each paper, in addition to recounting a specific discovery, tells a story in the broader context of the field,” he said. “That was a really big thing for me.”
Gaining the Skills Needed to Conduct Independent Research
During his second year, Clark worked with Sheybani to develop a research project he could conduct for credit. He took a number of ideas that she lacked time to pursue, put them together and gave them a new twist. At the same time, he began talking with Sheybani about applying for a Beckman Scholarship.
His first Beckman proposal was a continuation of his for-credit research. Although he was ultimately turned down, he gained a great deal from the process. “I learned how deeply you need to understand the work that you are proposing,” he said. “Equally important, I found out how crucial it is to be able to describe your plans to people outside your immediate field.”
With these lessons in mind, Clark applied again in his third year, and this time succeeded. “I think Dr. Price and Natasha had expected me to modify my original proposal, but I had been wanting to do a very different project,” he said. “This seemed like a perfect opportunity.”
Scientists have explored the use of high-intensity focused ultrasound to ablate cancer cells in a way that causes them to release damage-associated molecular pattern molecules to the cell surface or into the extracellular environment as well as specific tumor antigens. These are characteristic of cell death. Together, these substances prime the immune system to destroy tumor cells, no matter where they have traveled in the body.
Clark has designed a multistage experiment, allowing him to break this process down and learn more about its underlying mechanism. He cultures triple negative breast cancer cells, subjects them to focused ultrasound and determines if they have undergone immunogenic cell death. He will then inject these dead cells into a preclinical model and wait for an immune response. To test the effectiveness of this response, he will inject tumor cells into the model and assess whether they increase survival or reduce metastasis.
A Learning Opportunity for a Mentor
As his mentor, Sheybani has also benefited from working with Clark, but in a way that is relatively unusual in research laboratories, where the role of undergraduates is often to assist graduate students on their projects.
“Our undergraduate research program is squarely focused on undergraduates themselves, equipping them to undertake graduate-level research on their own,” Price said. “As a result, graduate students gain experience nurturing others, an essential skill if they hope, as Natasha does, to lead their own research laboratories.”