New cancer biologist targets ‘Achilles heel’ in deadly brain cancers

Cancer biologist Kathleen Mulvaney is bringing the hope of personalized medicine and early drug discovery to Virginia Tech and the Fralin Biomedical Research Institute at VTC, where she joins the faculty as an assistant professor on Oct. 1.

Her lab will be in Washington, D.C., on the Children’s National Research & Innovation Campus as part of a partnership between Virginia Tech and Children’s National. Both Kathleen Mulvaney and Jia-Ray Yu, an assistant professor in the research institute, will pursue treatments for childhood cancers in this new collaborative program.

Mulvaney knows intimately the pain of loss from the disease – and the promise of science to combat it.

She was always drawn to science. But in high school, Mulvaney’s father died of glioblastoma, a highly lethal brain cancer. Later, her mother survived an aggressive breast cancer thanks to a targeted cancer drug cocktail that didn’t exist a few years earlier.

“That really was a big push into the field,” she said. “It is personal. You see that in five or 10 years, there can be a new drug, and maybe we can make a difference in someone else’s family and in our lifetime. It's hard not to realize that what we're doing matters and that it works.”

Mulvaney saw Fralin Biomedical Research Institute creating a culture ideal for her and her research aims.

“I was impressed by the enthusiasm of the whole team,” Mulvaney said. “They are coming at the problem from a multi-pronged approach in ways that people don't often explore, so I saw a great opportunity to collaborate with people thinking outside the box in terms of how to treat brain cancers.”

The research institute’s relationships with clinical and research partners Carilion Clinic and Children’s National also was attractive, said Mulvaney, also an assistant professor in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine.

Mulvaney joins Virginia Tech following work as a postdoctoral associate with the Broad Institute of the Massachusetts Institute of Technology and Harvard University as well as the Dana-Farber Cancer Institute. She seeks to exploit a potential Achilles heel or genetic dependency in two rare but lethal cancers that afflict children: glioblastoma and malignant peripheral nerve sheath tumor.

Cancer is difficult to target with drugs because it’s a disease of mutations in previously normal cells. Mulvaney’s research aims to identify these genetic mutations and develop drugs to target them. Previous research from the laboratory where Mulvaney was a postdoctoral fellow lab has identified a key gene loss that is common in many cancers, especially in the two cancer types Mulvaney is targeting. In those cancers, loss of those two genes (CDKN2A/MTAP) correlates with poor survival rates.

“We really need to find ways to treat these tumors,” Mulvaney said.

The challenge, she said, is to develop a therapy that targets only the cancer cells while leaving normal cells healthy and intact.

Mulvaney hopes to develop a drug that targets a particular enzyme, PRMT5, that is crucial to a tumor’s survival and growth. Her aim is to inhibit that enzyme selectively in the tumor.

She plans to collaborate with Yu, her Virginia Tech colleague at the Children’s National Research & Innovation Campus. Yu’s research focuses on a different pediatric brain cancer, diffuse intrinsic pontine glioma, and their hope is together and in parallel to develop therapeutic approaches that can treat a range of pediatric brain cancers.

“I'm very passionate about this work leading to clinical trials that improve treatments of brain cancers in our lifetime,” Mulvaney said, “And I really do think that because of the tools that we have here at the Fralin Biomedical Research Institute and Virginia Tech, and the collaborations with Carilion Clinic and Children's National, this is the right place to get this done.”