MUSC student earns prestigious NCI fellowship for cancer research

When Thomas Blouin found out he received a highly competitive fellowship from the National Institute of Health (NIH), he was stunned.

“I never really thought I’d get it,” he said. “It was definitely unexpected.”

Blouin, a graduate student at MUSC, earned an F31 fellowship from the NIH’s National Cancer Institute (NCI). The NCI fellowship, which is awarded to fewer than 100 applicants each year, provides up to five years of funding to support predoctoral scientists in the field of cancer research. Receiving the fellowship signifies both current scientific excellence and strong potential as a future cancer researcher.

Under the mentorship of MUSC Hollings Cancer Center researcher Natalie Saini, Ph.D., Blouin will explore a deceptively simple question: How can a chemical that does not seem to change DNA directly still cause cancer?

The formaldehyde puzzle

The chemical Blouin and Saini will examine is formaldehyde – a common chemical we are all exposed to in small amounts. This exposure comes from the environment we live in, the products we use and even our own bodies.

“It's been a struggle reconciling this contradiction. Formaldehyde is associated with causing cancer, but it doesn't seem especially mutagenic. We thought maybe that’s because it’s harmful only to very specific regions of the genome.”

Thomas Blouin

However, exposure to high levels of formaldehyde can be harmful. It has been shown to damage DNA in several ways, and it is thought to be mutagenic, meaning it causes changes, or mutations, in DNA. These mutations are not always harmful – but they can be – contributing to diseases like cancer if the damage goes unrepaired. Formaldehyde has been linked to several cancers in humans and is even labeled as a Class I carcinogen by the International Agency for Research on Cancer.

Despite evidence of its cancer link, researchers have been stumped by a puzzling finding: Lab experiments often show that formaldehyde does not cause mutations in DNA, at least not under typical conditions. That paradox was the motivation for Blouin’s award-winning project.

“It's been a struggle reconciling this contradiction. Formaldehyde is associated with causing cancer, but it doesn't seem especially mutagenic,” he said. “We thought maybe that’s because it’s harmful only to very specific regions of the genome.”

Blouin and Saini hypothesized that the region might be single-stranded DNA, and formaldehyde contributes to cancer risk by damaging this vulnerable region.

DNA typically exists as a tightly wound double helix, with one strand protecting the other. But during certain events, like DNA replication, the strands separate, exposing their reactive bases. Blouin’s research will target these single-stranded moments when the genome is more vulnerable – and potentially more susceptible – to damage from formaldehyde.

A vulnerable genome

Luckily, Blouin is going in with strong evidence to support this research. His previous work in Saini’s lab demonstrated that formaldehyde is highly mutagenic in these regions. In the early experiments, exposing cells to formaldehyde led to a dramatic increase in the number of mutations they had – but only where single-stranded DNA was exposed.

“The promising results we already found gave us the confidence to keep pursuing this work.”

Blouin’s NCI-funded project builds on the strong foundation he has built by exploring how formaldehyde interacts with single-stranded DNA during replication. Replication is the process of cells making an exact copy of their DNA before dividing. It ensures that the next generation of cells has the correct genetic instructions. But, if errors are introduced during this process, cells can grow out of control – a hallmark of cancer.

Using yeast as a model system, Blouin already found signs of mutation clusters around replication sites. Now, he will look at whether similar patterns emerge in human cell lines when he disrupts replication by exposing the cells to formaldehyde.

Basic science with big implications

A key question driving the research is whether mutations are more likely to occur in single-stranded DNA seen during replication when that DNA is exposed to formaldehyde. If so, that could explain how a common chemical contributes to cancer, even though it does not cause widespread damage everywhere in the genome.

 

“If problems occur during replication – when cells are actively copying and multiplying –those cells can accumulate single-stranded DNA. We think that’s when formaldehyde does the most damage,” he explained. “Our goal is to understand how dysregulated replication forks might serve as hotspots for mutagenesis.”

Although the research is just beginning, its potential implications are broad. For instance, it could help to explain why people with certain inherited disorders involving mutations in replication or repair machinery are particularly vulnerable to formaldehyde (and related chemicals) and how that influences their risk for developing cancer.

Down the line, Blouin’s work could also shed light on how cancer cells survive a common treatment: chemotherapy. Chemotherapy damages DNA with the hope that cancer cells cannot replicate. But if cells find a way around that damage, they can survive and continue growing. Understanding how that bypass occurs could point to more effective treatments.

Powered by mentorship

Importantly, the F31 fellowship is not only about funding a project – it is about supporting a comprehensive training environment. Mentorship is an essential component, and mentors must demonstrate that they can help students grow scientifically and professionally, positioning them for a long-term career in cancer research.

Blouin is quick to point out how instrumental mentorship was to him receiving the grant and making this science a reality. His mentor Saini played a critical role, guiding him through the research process and motivating him during the many steps of the grant application. Also integral was David Long, Ph.D., whose veteran status as a graduate advisor at Hollings allowed him to offer invaluable insights and practical tips for crafting the application.

“Without their support and belief in me as a student, I would have never even applied for the fellowship,” he said.

Blouin’s research exemplifies the power of student science to have a real-world impact. With support from NIH and mentorship at Hollings, he hopes to help unravel a long-standing cancer mystery – and in doing so, open new doors for prevention and discovery.

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