image: Kathleen Mulvaney (at left) and her research team, including doctoral students Blanka Bordas and Cole Simon, research scientist Kaiyuan Zheng, and undergraduate research students Diya Chhabra of the University of Virginia and Sara Yoon from Duke University, explore how protein interactions affect tumors at the molecular level at the Fralin Biomedical Research Institute’s Cancer Research Center in Washington, D.C.
Credit: John Pastor/Virginia Tech
During every moment of any living organism’s life, enzymes are at work. These crucial proteins support life through most biological processes, including metabolism, movement, respiration, and digestion.
“Enzymes’ effects in cells are part of normal physiology,” said Kathleen Mulvaney, assistant professor at Virginia Tech’s Fralin Biomedical Research Institute at VTC. When cancer cells undergo damaging genetic changes, however, their environment becomes disrupted and they may become increasingly dependent on certain enzymes to survive.
In cases like these, an enzyme once associated with a normal function may be the only thing keeping a tumor alive.
Mulvaney and a team of researchers are studying an enzyme with a heightened role in cancers with certain genetic mutations. Their work will be funded by a $1.98 million National Institutes of Health grant designed to give early career researchers the flexibility to make new discoveries.
With the grant, the team looks to better understand one particular enzyme: protein arginine methyltransferase 5, or PRMT5.
“Fifteen percent of all human cancers have a gene deletion that makes them reliant on PRMT5,” said Mulvaney, a cancer biologist whose lab is based in the institute’s Cancer Research Center — D.C. “We know from our genetics work in the field that the cells are absolutely dependent on the enzyme, but we really don’t know why.”
Because of its association with genetically modified cancers, PRMT5 is often named as a potential target for cancer treatment. Though it shows therapeutic promise, Mulvaney said more answers are needed about the enzyme’s normal functions before considering its use in drug therapies.
“Why does your cell even care about this enzyme?” asked Mulvaney, who is also an assistant professor in the Department of Biomedical Sciences and Pathobiology of the Virginia-Maryland College of Veterinary Medicine. “What does it do? That’s important information because it helps us understand its role in normal cells and avoid potential side effects when targeting it for cancer treatment. Knowing this can guide the development of safer therapies.”
Over the course of the five-year grant, Mulvaney and her team will work to find these answers. They plan to use customized genome-editing tools that allow the team to reproduce the gene mutations that lead to altered PRMT5 activity.
For a lab that’s not yet 2 years old, Mulvaney said it is incredibly helpful to have National Institutes of Health (NIH) funding.
“It provides crucial funding for research that potentially may reduce the hardship of cancer, and it helps establish our lab in the field to be an NIH-funded laboratory,” she said.
By Lena Ayuk