The Next Use for mRNA?
Ana Fiszbein hopes to treat and prevent cancer
Among the many acronyms and initialisms that the coronavirus has thrown into our lives—COVID-19, PPE—one of the most promising is mRNA. It’s shorthand for messenger ribonucleic acid, a molecule found in our cells that transmits the essential genetic instructions to build, maintain, and repair our bodies. A lab-made mRNA has been powering lifesaving COVID vaccines.
Now researchers are delving into other potential uses for the technology, such as vaccines for Zika and malaria, as well as therapies for sickle cell anemia and cystic fibrosis. Biologist Ana Fiszbein is exploring mRNA’s potential to treat—and prevent—a disease that kills more than 600,000 Americans every year: cancer.
“In my family, there’s a lot of cancer history,” says Fiszbein, an assistant professor and Innovation Career Development Professor who joined CAS in January 2021. “If I can do anything to help cancer patients, that’s what I’m for.”
In the Fiszbein Lab, she studies gene expression—how mRNA transmits genetic blueprints from the DNA in the heart of a cell, the nucleus, to its construction site, the cytoplasm, a semifluid substance that fills the cell. By deepening our knowledge of how mRNA carries directions and how they’re put to work, she hopes to better understand what happens when the genetic process goes awry.
“I focus on cancer: what is different in terms of gene expression between a normal tissue and a cancer tissue. What is wrong, what’s happening, why these molecular mechanisms change, what triggers that,” says Fiszbein, who has received funding from the Massachusetts Life Sciences Center and BU’s Rafik B. Hariri Institute for Computing and Computational Science & Engineering.
In some studies, Fiszbein and her team look at one gene in detail. In others, they use computing power and machine learning to look at what’s happening across the entire genome, a vast amount of data. “We mix experimental and computational work,” she says.
In a recent study, Fiszbein found that the journey from gene to protein doesn’t flow in just one direction. When it comes to alternative splicing, instructions can be passed back from a protein to support development elsewhere in the body. “The mRNA processing feeds back to transcription and mRNA synthesis,” she says.
“During cancer progression, there are many genes where we can change this splicing,” says Fiszbein. Eventually, it may be possible to teach the body to reject a cancer’s harmful cell differentiation instructions. “We’re trying to first understand what’s going on and then we develop strategies to manipulate that.”