When Ramon Castellanos, a biomedical engineering major at Florida International University, opted to make the most of the summer between his junior and senior years by applying for a National Science Foundation "Research Experience for Undergraduates" program, he had no idea he had made a life-changing decision. But after 10 weeks as a student in the program in Multi-Scale Systems Bioengineering at the University of Virginia, the outlines of this change were clear.

Castellanos had been introduced to agent-based modeling, a powerful computational technique used to model complex systems. He began thinking that a career in research might be more satisfying than one in medicine; and he gained insight into the type of graduate school he might like to attend.

The upshot: Castellanos arrived in Charlottesville in August 2019 as a doctoral student in biomedical engineering, where he will use agent-based modeling to model microcirculation. He will work in the lab of Shayn Peirce-Cottler, professor of biomedical engineering and the department’s graduate program director.

“I am really excited by the direction I am pursuing,” Castellanos said. “The UVA program played an important role in where I am now.”

Portrait of Ramon Castellanos

As a doctoral student at UVA, Ramon Castellos will use agent-based modeling to model the microcirculation in the lab of BME Professor Shayn Peirce-Cottler.

Delivering a Customized REU

Timothy Allen, associate biomedical engineering professor and the principal investigator of the research experience program, chose Castellanos as one of 11 students from a field of more than 200 applicants. In addition to selecting students he feels are the most enthusiastic and serious about research, Allen identifies two or three faculty members whose research best matches students’ expressed interests.

“Of the students we admit, 95 percent accept our invitation,” said Peirce-Cottler, one of 18 faculty members from UVA Engineering, the School of Medicine and the College of Arts and Sciences who open their labs to students. “This is an indication of just how much time Timothy puts into the admissions process, and how effective the selection and matchmaking processes are.”

Mastering Agent-Based Modeling

During his time in the undergraduate research program, Castellanos joined the UVA Multiscale Muscle Mechanophysiology Lab run by Silvia Blemker, biomedical engineering professor.

Castellanos worked with Blemker’s team studying Duchenne muscular dystrophy, a devastating neuromuscular disease affecting one in 3,500 boys. Among other techniques, the group employs agent-based modeling to study the injury response in dystrophic muscle. Children with Duchenne can appear as though their muscles have not atrophied because fat replaces lost muscle tissue. Blemker challenged Castellanos to create an agent-based model of this fat infiltration that could be incorporated in their larger disease model.

“Agent-based modeling was new to me,” Castellanos admitted, but he dove right in, reading articles over and over until he felt he understood them.

“Virtually everyone I encountered across the department took an interest in what I was trying to accomplish,” Castellanos said. “People took the time to answer my questions, even when they were walking out the door at the end of the day.”

This approach is part of a deliberate effort to build undergraduate research students’ skills and confidence.

“We aim to foster a positive environment for our REU students, helping ensure that they appreciate the contributions they are making and encouraging them to try new things,” Blemker said. “For students like Ramon who are already very independent, my job is to encourage them but stay out of their way and let them enjoy the satisfaction of building something new.”

In Blemker’s estimation, the model Castellanos produced at the end of the session was far ahead of what she would expect from a graduate student.

Blemker M3  lab Summer 2018

For the REU, Castellanos spent ten weeks in BME Professor Silvia Blemker's M3 Lab, working with the team studying Duchenne muscular dystrophy.

Rethinking Career Goals

Before he arrived at UVA, Castellanos’ career path appeard to lead directly to medical school. He had spent more than 500 hours shadowing physicians at a local hospital and collected letters of recommendation from each one. But he never entirely ruled out graduate school. “I was about 60 percent sure that I wanted to be a physician rather than a researcher,” he said.

Although his senior capstone project at Florida International was the decisive factor in making the switch, the odds began to change at UVA. “When you do research, you are breaking new ground,” Castellano said. “People can give you tips and guidance, but you are ultimately on your own. I liked that feeling.”

In effect, Castellanos’ experience at UVA gave him a taste of graduate school. “I realized that the work I put in during the undergraduate research program was just a fraction of what’s required of a graduate student, but it was enough to give me a sense of what that would be like.”

Castellanos also gained insights about how to evaluate and apply to graduate school, thanks to a series of presentations he attended that were part of the program. “I left UVA with a blueprint about going forward if I opted for graduate school,” he said. “It turned out to be very helpful.”

Choosing Biomedical Engineering at UVA

After Castellanos changed his career goals, his experience in the undergraduate research program meant that UVA was high on his list of graduate schools. He had been impressed by the depth of UVA’s biomedical data sciences expertise and by how approachable the faculty are.

He had also made a real connection with Peirce-Cottler, thanks to the periodic poster sessions Allen schedules over the course of the summer. A conversation at a poster session led to an hour-long discussion for Castellanos in Peirce-Cottler’s office, where she described the work underway in her lab and her expectations for her graduate students.

“Other schools told me they wanted me to author a certain number of papers as a grad student,” he said. “At UVA, the emphasis was on devoting your time to research, so that when you write a paper, it’s really good. That definitely played a role in my decision.”

Ultimately the defining factor for Castellanos was the close relationship between the Department of Biomedical Engineering and the UVA Health System. “I see it inspiring future tissue engineering research that will have a real impact,” he said.

Mentoring undergraduate research students also gives faculty members a head start in recruiting graduate students to fill openings in their labs. Normally during Ph.D. student recruitment, Peirce-Cottler said, “we read applications and interview applicants on the phone, and if we are lucky, we get to meet with them briefly during an on-Grounds visit. Ultimately, we have to make a decision about someone we are going to be working closely with for the next five or so years of their Ph.D. training on the basis of limited information. This program gives faculty and students a chance to really get to know one another before we make these long-term commitments.”

Peirce-Cottler feels great about her decision to invite Castellanos into her lab. “He’s got a real vision for what he wants to achieve in graduate school, he’s excited by our research, and he shows tremendous grit and determination,” she said. “I feel confident that he’s going to be a great addition to my lab and to our biomedical engineering graduate program.”

What Is Multi-Scale Modeling? How Can It Help Your Health?

In this op-ed in Forbes, Dr. Bruce Lee of Johns Hopkins writes about BME Professors Shayn Peirce-Cottler and Silvia Blemker, asserting that their work is an example of how multi-scale modeling promises to fundamentally shift how health and medical research are approached.

Multi-Scale Modeling of Duchenne Muscular Dystrophy

"It's really a brand new idea in the field of modeling, that we can link scales and develop models that can predict the outcome of a drug therapy."