When Good Proteins Go Bad

Cancer Research with Frida E. Kleiman

Frida E. Kleiman is out to prove that the proteins p53 and BRCA1 “are really good guys” despite their bad reputation. Their unfortunate ignominy is due to the fact that when they are not functioning normally, cancer often occurs.

“They become bad when they are mutated,” explains Kleiman, an assistant professor in the Ph.D. programs in biology, chemistry and biochemistry. “When they are working properly, they are our best friends in fighting cancer.”

In fact the two proteins, when operating correctly, are significant tumor suppressors. When a cell loses its function, it can grow into a cancer cell. In a process called transcription, p53 and BRCA1 help to activate other proteins that help repair DNA when it has sustained damage. They can also control the cell growth cycle to prevent cancer from spreading or activate apoptosis, a course of action to kill the cells altogether if the damage proves to be irreparable.

“There are many wonderful things that these proteins do,” says Kleiman, who joined the chemistry department at Hunter College three years ago. “Most scientists haven’t paid as much attention to their effect on RNA processing.”

She says that most of the previous research on p53 and BRCA1 has focused on studying their role in other cellular processes, but not in RNA processing, the method by which messenger RNA carries information from the cell’s nucleus to synthesize proteins. Some of those proteins could help repair damaged cells. While she was a postdoctoral fellow at Columbia University, her research group discovered the connection between BRCA1 and RNA processing.

“It’s important in understanding how the body responds to DNA damage,” Kleiman says.
Her latest project, which she says she expects to be working on for the next five years, is funded by roughly $1 million in grants from the National Institutes of Health and from the U.S. Department of Defense. The project involves growing DNA cells in a culture by feeding them nutrients, then exposing the cells to ultraviolet light—which will cause mutations—and then purifying the cell’s nucleus to observe how different proteins interact. She compares the response to how the same proteins interact in a control cell that has not been exposed to the UV light.

“We check the cells one minute later, then two minutes later, 10 minutes later, and then several hours later,” she says. “Each step along the way we want to see how the different proteins are interacting.”

She says the study will try to identify exactly which proteins run amok when cells have been damaged and may lead to clues on how to regulate gene expression by RNA processing.
“Everyone is looking for the cure,” she says. “My work won’t necessarily help find the cure but it will possibly help us to understand how to make better drugs that help cells function properly. That’s a step.”

The Argentina-born scholar received her master’s degree and her Ph.D. in chemistry from the National University of Cordoba.

She says she originally want-ed to be an actress but her parents wouldn’t hear of it. So she fell back on a subject that she always loved in school, biochemistry. She discovered her niche when she realized that not many scientists were studying RNA. She further discovered that she would have a lot of freedom by doing what is essentially biological research in a chemistry department.

“I’m working in a very rich field,” she says. “I will have plenty to do.”