Two George Washington University Integrated Biomedical Sciences PhD candidates, Trace Walker and Kevin Nestler, are pushing forward ovarian cancer research while navigating the early stages of their scientific careers. Working under the mentorship of Katherine Chiappinelli, PhD, associate professor of microbiology, immunology, and tropical medicine, both researchers recently earned highly competitive early career awards that promise to fuel their work and shape their next steps.
Both Walker and Nestler point to the same source of steady guidance.
“Kate is an incredible mentor,” said Walker. “She leads with both rigor and compassion, reminding us that science is about persistence as much as precision. Science is tricky, and it’s messy. What matters most is doing high-quality work that genuinely pushes the field forward.”
Although their projects unfold in the same lab space, the budding researchers travel different routes through the biology that allows ovarian cancer to spread and evade the immune system.
Tracing Hidden Genetic Signals
Earlier this year, Trace Walker received a six-year National Institutes of Health F99/K00 grant for his study, “Transposable Element Regulation and Expression During Cancer Progression.” The grant program spans the late stages of doctoral training through postdoctoral work, supporting young scientists as they navigate a critical career transition.
“This is the first time the F99/K00 grant from the National Cancer Institute (NCI) has been awarded to someone at GW, which makes it even more exciting,” Walker said. “It’s a big step toward independence; having my own funding means I can bring my own ideas to my next lab and begin developing them into long-term projects.”
Walker’s project emerges from DNA’s quieter corners. “DNA has large ‘hidden’ regions that can produce RNA sequences resembling viruses,” he explains. These transposable elements (TE) usually lie dormant. When activated, he explained, they can “trick the cell into thinking it’s infected.”
“When that happens, the immune system can be alerted to destroy the affected cells,” Walker said. “My research looks at how cancer cells keep these viral-like sequences turned off, and what happens when they don’t.”
Walker focuses his research on the protein p53, often referred to as the ‘guardian of the genome.’
“I’m studying how it can both activate and silence transposable elements,” he said. “The big question is: how do cancer cells use this mechanism to stay under the immune system’s radar, and how can we turn that invisibility off?”
The p53 gene helps regulate cell division and trigger cell death when DNA damage emerges, but in ovarian cancer, p53 frequently mutates.
“Mutations in p53,” explained Walker, “lead to major changes in which transposable elements get turned on.”
Instead of triggering an immune alarm, the response weakens. Walker believes this gives tumor cells an advantage. “We’re still figuring out whether that’s a direct effect of how p53 binds DNA, or if it’s acting through other genes. Either way, it’s clear that mutant p53 helps create a kind of ‘stealth mode’ for cancer cells.”
Rewriting Cancer’s Molecular Messages
While Walker studies how tumors stay hidden, Kevin Nestler looking for ways to expose them. Nestler received an F31 award for his project, “Role of RNA Methylation in the Regulation of Viral Mimicry in Ovarian Cancer.” The two-year Ruth L. Kirschstein National Research Service Award supports predoctoral researchers with stipends, tuition support, and funding for research materials and travel.
Nestler aims to understand why the immune system fails to recognize ovarian tumor cells. He investigates a process called viral mimicry, in which cancer cells create an illusion of viral infection. When this illusion works, killer T-cells move in and destroy the affected cells.
About half the human genome consists of transposable elements (TE), explained Nestler, “ancient, virus-like fragments of DNA” that usually stay silent. Epigenetic therapies can reactivate RNA from these TEs, prompting immune system alarm bells to sound.
“The goal,” he said, “is to flip a cold tumor, one that hides from the immune system, into a hot tumor that’s full of immune activity.”
Many tumors already contain TE RNA but still manage to evade detection. Nestler suspects RNA modifications hold the answer. Chemical marks, known as the epitranscriptome, shape how cells interpret RNA. He describes these marks with an editorial metaphor: “Writers,” enzymes that add marks; “readers,” proteins that interpret them; and “erasers,” which remove them.
Nestler focuses on N6-methyladenosine (m6A). “We think the presence of m6A on RNA derived from these transposable elements might actually stop them from forming RNA that causes an immune response,” he says. “That would prevent the immune system from recognizing and attacking the tumor.”
His project tests whether blocking the writers that add m6A might help unmask tumors. By combining the m6A inhibitor with epigenetic therapies that activate transposable elements, Nestler hopes to generate a more sustained immune response. “If we can remove the cancer’s ability to hide, we might make other immunotherapies like checkpoint inhibitors more effective,” he says.
A Lab Built on Curiosity and Steady Guidance
In the Chiappinelli Lab, both researchers develop their ideas in an environment grounded in rigor and support. Their work tackles different layers of ovarian cancer biology such as mechanical stress, genetic regulation, RNA editing, but their paths converge in their mentor’s office.
Their discoveries aim to reveal what cancer hides and to show the immune system what it has been missing. In doing so, they carry forward a shared commitment to careful inquiry, patient experimentation, and the slow, deliberate uncovering of what drives disease.
Their awards mark a step forward, but their ongoing investigations mark something deeper: a lab steadily shaping new ways to see, and disrupt, the molecular strategies cancer uses to survive.
