Engineering proteins to treat cancer
PhD student Oscar Molina seeks new ways to assemble proteins into targeted cancer therapies, while encouraging his fellow first-generation graduate students.
Like many children of first-generation immigrants, Oscar Molina grew up feeling like he had two career choices: doctor or lawyer. He seemed destined for the former as he excelled in high school and planned to major in biochemistry at the University of California at Los Angeles, but as an undergraduate, he fell in love with research.
“I was fascinated by discovery. As I did it more in college, I realized I didn’t want to be a doctor,” he says. “Once I saw that I could make an impact and be at the forefront of therapy with biotech, I knew I wanted to do that.”
If the next couple of years go as planned, his parents will indeed see their son become a doctor — just not exactly the way they might have guessed. He’s entering the fifth year of his PhD program in biology at MIT and is currently working in the lab of Professor Ronald Raines, researching the potential of proteins to kill cancer cells.
Molina, who is the first in his family to attend college, also works to support his fellow students through outreach and community-building efforts. In various roles, including as a Graduate Community Fellow in MIT’s Office of Graduate Education, he sought to connect and encourage students from underrepresented backgrounds as they pursued their own graduate studies.
“I had a lot of opportunities presented to me that made me ask, ‘Why me?’” he says. “I recognize that they were super valuable, and that’s why I should deliver that back to other people.”
Unlocking protein construction chemically
The spirit of giving back isn’t just limited to Molina’s work outside of the lab. He chose chemical biology and the pursuit of new cancer therapies as his research focus partly because his grandfather has been dealing with the disease for the last 10 years. The ultimate goal guiding his research is to make all protein-based cancer therapies more effective.
He and other collaborators in the Raines Lab published a paper in June that takes an important step in that direction, suggesting a way to make fusion proteins with greater customization and improved performance. They discovered that a chemical called 3-bromo-5-methylene pyrrolone can be used to combine three proteins efficiently and with high levels of control and modularity, a significant advance given most of the techniques for protein conjugation are only able to combine two at a time in a single spot.
“Now, we can have chemical control of where we include different things, where we can kind of plug-and-play,” he says.
Researchers can now adjust multiple characteristics at the same time — for example, increasing the protein’s half-life or improving its ability to target cancer cells — while still achieving a homogenous end product. They’re also relevant to immune cell redirection therapies, which require multimeric protein chimeras to activate immune clearance of cancer cells.
“That’s the most interesting thing to me,” he says. “How do we give a biologic therapy the best opportunity to be active and efficacious?”
His upcoming thesis will center around that question as it relates to chemotherapies based on ribonuclease 1, an enzyme that is best-known for cleaving RNA.
Paying it back and paying it forward
While that thesis will likely demand more of Molina than any other project he’s worked on in the past, he’s no stranger to hard work. After his mother and father left their respective homes of Guatemala and El Salvador in the 1990s, they dedicated their lives to giving their children futures that they themselves didn’t have access to.
Witnessing their efforts impressed two beliefs into Molina’s worldview: the value of education and the importance of support. Among his family, he is the first to graduate from a U.S. high school, the first to attend a four-year college, and the first to attend graduate school. These “firsts” can weigh heavily, and as he began his studies at MIT, he knew how difficult it can be to carry that burden alone.
“I saw the need and wanted to help other people be the first in their family to do things like go to college,” he says. “I also wanted to help people with similar backgrounds to mine, like being an underrepresented minority or a first-generation college student.”
That desire led Molina to join MIT’s Office of Graduate Education as a Graduate Community Fellow in January 2022, where he worked on supporting various affinity groups across the Institute. This included helping groups out with logistics, funding applications, community outreach and cross-group collaborations. He also spent part of last summer as a pod leader for the MIT Summer Research Program, which works to prepare underrepresented students for graduate education and research.
He’s also leveraged his personal interests to volunteer with various community organizations in Cambridge and Boston. Despite his numerous commitments, he’s an avid marathon runner, and ran the 2022 Boston Marathon while raising nearly $8000 for Boston Scores, a program that provides educational and athletic opportunities for students in the Boston Public Schools system.
After graduation, Molina plans on joining a startup in Boston’s biotech scene while learning more about the venture capital firms that fund their research. Wherever he ends up, he plans on continuing to apply the core truths that brought him where he is now.
“I want to be at the forefront of creating therapies. I really like science. I really like helping others. I really like the ability to create things that are impactful,” he says. “Now it’s time to take that and find my way to what’s next.”
