What can yeast and fruit flies tell us about cancer

Professors of Biology Oliver Kerscher (left) and Matthew Wawersik have worked at William & Mary for over 20 years. Friends and colleagues, they've combined their expertise to study PINX1, a gene involved in cancer. (Photo by Stephen Salpukas)

Most people pay little attention to flies, unless they're swatting them away from their food. But for William & Mary Biology Professor Matthew Wawersik and his students, these pesky insects could hold the clues for future cancer therapies.

Along with Professor of Biology Oliver Kerscher's yeast lab, this group is using a simple organism to study one of the most complex diseases - supporting the mission of World Cancer Day.

Asking questions with model organisms

But what do flies and yeast have in common with people? As it turns out, quite a lot.

"There are over 2,000 conserved genes between yeast and humans," said Maddie Farrington '25, a graduate student in Kerscher's lab. "These genes encode for some of the same fundamental processes, allowing us to use yeast as a model organism to understand basic human biology. Think of yeast as single-celled humans."

Fruit flies, Drosophila melanogaster, also contain orthologs, genes that are believed to mimic the function of their human counterparts. Studying this insect gives scientists a more complex, but still relatively simple and tractable system in which to examine cell-cell interactions.

When it comes to disease research, model systems can be especially valuable as they provide a relatively cheap, fast and easy way to ask important questions.

"Understanding how a certain protein is involved in something like cancer is extremely complicated," said Farrington. "If you look at a diagram of protein interactions, you'll see what I'm talking about. One protein is like a tiny piece in a giant machine. Changing that piece or removing it can impact the overall function of the machine in ways we might not anticipate."

Model systems, Farrington explained, help scientists map out a protein's basic biology, including where it operates in the cell's machinery and what role it plays. These questions can be very complicated to answer using human cells.

"Because of their robust nature, many human cell lines used in research are already cancerous, which makes it hard to make inferences about how proteins in healthy cells behave," said Wawersik. "Whereas in my lab's flies, we can study healthy function and then induce cancerous behavior. This helps paint a picture of what is really going on."

In the case of their current collaboration, Wawersik and Kerscher are using flies and yeast to study PINX1, a gene implicated in cancer with a confusing twist.

Solving the puzzle of PINX1

PINX1 has a complicated relationship with cancer. In cancers like breast and colon cancer, it's known as a tumor suppressor, meaning it helps keep cancer in check.

"We know PINX1 plays an important role in keeping a cell's lifespan finite," said Kerscher. "It does this by regulating caps on the ends of our chromosomes called telomeres. Without regulation, telomeres can build up and virtually make cells immortal - one of cancer's main calling cards. So, it makes sense that you'd see decreased levels of PINX1, a gene that's helping maintain a healthy cell lifespan, in cancer."

But in other cancers, PINX1 levels are increased, suggesting this gene's role in cancer is more complex. Using flies to uncover how PINX1-like genes behave in living tissue and yeast to map their molecular interactions, Wawersik and Kerscher hope to paint a fuller picture of PINX1's function.

They're already making some intriguing discoveries.

"We actually discovered a PINX1 ortholog in fruit flies thanks to students taking Kerscher's genetic analysis lab class," said Wawersik. "We've since been able to show that when this gene, which we call Chigno, does not function properly, stem cells grow out of control and form tumor-like masses in the reproductive organs, leading to infertility."

Wawersik highlighted that this finding is especially intriguing as human PINX1 is most abundant in male reproductive cells, and certain testicular cancer cells have altered levels of PINX1. Dissecting Chigno functions in fruit fly testes, therefore, has implications for the study of human reproductive cancer and infertility.

In another unexpected finding, the team discovered that Chigno interacts with a protein called SUMO, which just happens to be a central focus of Kerscher's lab.

"SUMO is involved in the robustness of cancer, how treatment resistant it is, how fast it grows," said Kerscher. "So, it was an incredible coincidence and very exciting discovery for us to make the link between Chigno and SUMO."

Kerscher's graduate student, Farrington, has found initial evidence that yeast PINX1 levels vary during the cell cycle and that SUMO may play a role in that regulation.

"If PINX1 is involved in regulating the cell cycle, as our preliminary work suggests, it becomes an even more compelling candidate in cancer research," said Kerscher. "Small disruptions in genes that control the cell cycle can have outsized effects on how cells grow and divide."

Laying the groundwork

While this work is still far from clinical application, it is helping clarify how PINX1 functions - an essential step toward any future therapy.

"Without the basic research there is nothing to translate into clinical findings," said Kerscher. "While we're in early stages, there's a lot of hope for the advancements this work could inform."

That aspiration resonates with students working on this project, some of whom know firsthand the toll cancer can take.

"What we're doing is laying the groundwork for future therapeutics," said Carolyn Payne '26, a student in Wawersik's lab. "As someone whose family has been touched by cancer, that's really motivating. Even if I only make the smallest difference, that is worth it for me."

Training the next generation of scientists

Not only are flies and yeast ideal media for asking questions related to human health, but they are a great way to teach students research.

"In just three weeks, I can teach students everything they need to know to get started with experiments," said Kerscher. "That allows them to get down to doing research quickly and master the skills they'll need for careers in science."

That was the story of Zac Elmore M.S. '11, a former student in Kerscher's lab. Elmore is now co-founder and chief scientific officer at Lucidigm Therapeutics, a startup developing enzyme-based drugs to regulate the immune system.

"It was at William & Mary where I really learned what it takes to be a professional molecular biologist," said Elmore. "Being exposed to such a high level of expertise along with a rigorous research focus allowed me to grow more as a scientist than any other period of training in my professional career."

Learn more about the Wawersik and Kerscher research labs.

Catherine Tyson, Communications Specialist

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