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Proteins and Pavarotti: How One Scientist Forged His Own Path

Posted on Wednesday, July 5, 2017
By Paige Allen
Originally published in Forward, Spring/Summer 2017

Roland L. Dunbrack, Jr, PhD [photo: Gene Smirnov]Roland L. Dunbrack, Jr, PhD [photo: Gene Smirnov]Roland Dunbrack was a toddler when Stanley P. Reimann died. But Reimann — founder of the Institute for Cancer Research, which evolved into Fox Chase Cancer Center — shared some striking similarities with the scientist Dunbrack has become. They share a love of the performing arts, an interest in learning about the wider world outside of science, and a philosophy of research that encourages searching in unexpected places in order to answer important questions about cancer.

Growing up in the suburbs of Boston, Dunbrack, 53, found himself pulled to math and science. Chemistry, physics, biology, and math — he loved it all. Over the years he found a way to blend the different disciplines, and has become a renowned computational biologist. Today he is a pioneer in a field of science that barely existed when he was a student.

In 1981, sitting in a freshman chemistry course at Harvard University, Dunbrack was fascinated watching a computer simulation of a protein. He soon realized he could apply what he knew about one area of science to others.

“I liked physics and mathematics but I could also apply it to biology,” he said. “There wasn’t a sharp divide. I could be a person trained in computing and physics and apply it to the world of biology.”

After his sophomore year, he first tried working in a lab, where he quickly learned the value of good mentors and how to rebound from mistakes.

Following graduation, Dunbrack found himself at a crossroads, personally and professionally. Seeking a change of scenery, he swapped Cambridge, Massachusetts for Cambridge, England. There, Dunbrack focused his studies on biochemistry and computational chemistry.

Roland and his team, Maxim Shapovalov, Simon Kelow, and Vivek Modi. Roland and his team, Maxim Shapovalov, Simon Kelow, and Vivek Modi.

After two years overseas, Dunbrack was recharged and ready to enroll in Harvard once again, this time for a doc­torate in biophysics. His PhD mentor was Martin Karplus, winner of the 2013 Nobel Prize in Chemistry, and the pro­fessor from that very same freshman chemistry class.

He began a focus in graduate school on how to pre­dict the structures of proteins, and that focus continues some 30 years later. Using computers, he built models of newly identified proteins based on the known structures of related proteins. This kind of work provides other scientists a more precise un­derstanding of how a given protein functions, and enables them to devise more precise experiments.

In 1997, following the comple­tion of his postdoctoral fellowship at the University of California San Francisco, Dunbrack returned to the northeast, to accept a position at Fox Chase. Before long, he was collabo­rating with his new colleagues across the Center to model the proteins they were working on.

In a time before computers became ubiquitous, Dunbrack showed researchers from various disciplines that they could be used to rapidly advance sci­entific discovery.

As technology crept into every aspect of life, and people generally became more comfortable using computers, Dunbrack developed numerous software programs that are in use by thousands of scientists and researchers around the world today.

At Fox Chase, as more people got wind of Dunbrack’s work, more projects came his way. In 2003, the Center re­ceived a grant to start a molecular modeling facility, which allowed for a dedicated staff member.

“It’s fun because I’ve learned a lot of biology, especially cancer biology,” he said. “I learn something new every time someone comes to me.”

With his students, Dunbrack has performed extensive statistical studies of detailed aspects of protein structures. These statistical analyses are used in most of the protein structure prediction and design programs developed in labs around the world.

In recent years, he has turned his attention to the design of proteins – using the computer to design new amino acid sequences that produce proteins with new functions. He is applying this technology to designing new antibody drugs against cancer.

BUILDING HIS TEAM

Over the years, Dunbrack has built a close-knit and diverse lab.

After meeting Dunbrack in India, Vivek Modi, a postdoctoral fellow, joined the lab in 2013. Modi was interested in Dunbrack’s field of work and knew there was nowhere better to train.

“Roland’s lab is one of the best places in the world in this area,” he said. “It’s kind of a dream come true to work with Roland. He’s not just a great scientist, he’s a great human.”

Maxim Shapovalov first met Roland in 2003, when he was an exchange student from Russia collaborating with Fox Chase during a thesis project. He rejoined the lab in 2006 as a programming analyst.

“Working with Roland, I was exposed to the beauty of biology and math,” he said. “Roland is not just a mentor, he’s a very good friend.”

Qifang Xu joined the lab in May 2005, when she was a graduate stu­dent studying computer science at Temple University. Upon receiving her PhD, she completed her postdoc­toral fellowship at the lab and stayed on as a research assistant professor.

Simon Kelow, a graduate student at the University of Pennsylvania, joined the lab in May 2015. He started out as an astrophys­icist but quickly became enthralled with protein structure prediction and protein design, making him a perfect match to join Dunbrack’s lab.

Training and working with one of the world’s experts in the field is inspiring, Modi said, especially since Dunbrack has fostered a positive environment that allows the group to flourish.

“He doesn’t put pressure on us,” Modi said. “We feel mo­tivated but we don’t feel any pressure. We have a lot of fun in the work we do.”

The group is very tight, socializing regularly, going ski­ing, and celebrating the Chinese New Year together.

“There’s so much you can learn from him,” Modi said. “You can talk about all different things, from history to politics to science to everything else.”

Working collaboratively with Dunbrack and the team, Mark Andrake leads the Center’s molecular modeling facility.

“The lab is pioneering new discovery in cancer biology using computational methods and they’re also pioneering the methods themselves,” Andrake said. “The modeling facility is the liaison to other labs that can access and use the methods they’re creating.”

All of Fox Chase’s research programs use the facility, and due to the collaboration, either Dunbrack or Andrake co-au­thored some 30 scientific papers between 2010 and 2015. One of the more notable studies involved analyzing genetic mutations to determine which patients would and would not respond to chemotherapy for bladder cancer. Those findings are helping to bring personalized medicine closer.

With his dual role as a biochemist and manager of the modeling facility, Andrake has a deep understanding of the value Dunbrack and his group provide.

“It’s fun to be able to have minds from different areas of expertise applied to the problem at hand,” he said. “There’s a great synergy here.”

BREAKING THE MOLD

Dunbrack feels his responsibility to his team extends beyond the lab. On any given afternoon, it’s not uncommon to find them at Fox Chase’s daily tea time, a tradition that dates back to the 1940s that was devised to foster collaboration amongst the researchers and clinicians across the Center.

Xu appreciates the family-like atmosphere that Dunbrack encourages in his team.

“I feel this group is my second family in the United States,” she said. “Roland treats everybody respectfully and equally, and keeps our group diverse.”

Outside the lab they have free-flowing conversations about topics ranging from food to cultural differences to world politics.

“It’s good to get a break from the science,” Dunbrack said. “I want them to be comfortable talking about anything. They’re going to be inter­viewing for faculty jobs and they have to learn about more than just science.”

Dunbrack’s lab members appreciate the inclusive atmosphere and the chance to learn about one another’s backgrounds and interests.

“He encourages us to think about and engage in topics outside of the lab and science while applying the same measure of intellectual ambition,” Kelow said. “As a black student, I’ve often felt out of place in various science are­nas, but being able to openly discuss problematic mindsets in society is helpful and he encourages that.”

Dunbrack wholeheartedly embraces his hobbies, as well. In college, he took clarinet, piano and art history classes. He’s an avid cyclist, and as a resident of South Philadelphia, he loves exploring the city’s offerings, espe­cially the theater and opera.

Many of his close friendships have come through his participation in the city’s singing groups. He previously belonged to the Philadelphia Gay Men’s Chorus and now sings with the Philadelphia Voices of Pride.

“It’s just fun to sing,” he said. “It’s so different from what I do in my day job. It’s a great stress relief.”

While modeling the structures of proteins and singing don’t often go hand in hand, Dunbrack has found that his interests occasionally do overlap. He invited his lab mem­bers to one of his recent performances and was touched to find most of them attended.

“I was really moved when they came to my concert,” he said. “It made me very proud that they wanted to come.”

Dunbrack’s wide variety of interests and openness to ex­ploring new opportunities and experiences isn’t a surprise to those who work with him.

“Roland is an amazingly bright, creative scientist. He moves so fast sometimes that I can barely keep up with him,” said Andrake. “As a scientist, his openness makes a lot of sense. It’s a sign of someone who has the creativity to pioneer new visions.”

One can assume that Reimann would feel his institute is in good hands with scientists like Dunbrack continuing his legacy.

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