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Toshio “Toshi” Tsukiyama, PhD, DVM, professor and associate director of the Basic Sciences Division at Fred Hutch Cancer Center, has received the inaugural David and Deborah Lycette Endowed Chair for Cancer Research.
The new endowed chair, established by a couple who have been involved with Fred Hutch since its earliest days, will advance precision oncology by supporting Tsukiyama’s research into how cells package, store and use genetic material.
With a gift to endow a faculty chair, visionary donors empower scientists to pursue transformative ideas. Generous supporters have endowed 55 chairs at Fred Hutch to date, honoring faculty members and giving them flexible funding for innovative research. Endowment gifts are critical to long-term sustainability and a cornerstone of the Campaign for Fred Hutch, which is bringing the community together to increase the pace and scale of discovery.
“Dr. Tsukiyama is changing the way we think about fundamental aspects of biology,” said Fred Hutch President and Director Thomas J. Lynch Jr., MD, holder of the Raisbeck Endowed Chair. “He is cracking the code that controls how cells turn genes on and off, which is essential for knowing what goes wrong in cancer and what to do about it.”
“Receiving this endowed chair is a game changer for my lab — it will help with every aspect of our research,” said Tsukiyama, who trained as a veterinarian in Japan before discovering a passion for microbiology. He went on to earn a PhD before coming to the U.S. for a postdoctoral fellowship at the National Institutes of Health in Bethesda, Maryland.
The power of sleeping cells
Since joining Fred Hutch in 1997, Tsukiyama has focused on chromatin, the molecular scaffolding that makes it possible for a seven-foot strand of DNA to precisely tuck, fold and wrap itself into a microscopic bundle that fits into the nucleus of a cell. Chromatin arranges DNA to make genes accessible when they’re needed. And it plays a critical role in cell division, ensuring DNA is divvied up correctly in the new daughter cells.
Tsukiyama’s research has revealed that chromatin is also vitally important when cells are not dividing but are in a dormant phase, called quiescence.
“For a long time, researchers weren’t interested in quiescent cells because they didn’t seem to be doing anything,” said Tsukiyama. “But it turns out that these sleeping cells are important, both for normal life and for cancer biology. For me, this field has been a research gold mine.”
For example, quiescence may explain how some cancers evade drugs, recur and spread. Because many drugs target rapidly dividing cells, cancer cells can avoid detection by going to sleep — and they can stay asleep for months or years before becoming active again. Quiescent cells may also move stealthily from one part of the body to another, helping cancer spread.
“If we can find a way to detect these cells and wake them up artificially, we can make them more sensitive to drugs,” Tsukiyama said. “But we don’t know how to do that yet. First, we need to understand how cells stay dormant for that long and what’s special about them during quiescence that we can change to make them more active.”
This knowledge, which can only be gained through fundamental research, will lay the groundwork for better therapies.
His lab’s focus on sleeping cells, he said, started “in the most Fred Hutch way imaginable” — a hallway conversation with a colleague. That’s where geneticist Linda Breeden, PhD, who is now retired, floated the idea of leveraging Tsukiyama’s molecular biology expertise to deepen her genetics-focused research on cell dormancy. Their collaboration started in 2012 with a pilot project. But soon “it got so interesting that now the entire lab studies different aspects of dormancy,” Tsukiyama said.
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As technologies have become more sophisticated, so have the questions his team can ask and answer about the underlying processes triggered by chromatin remodeling, the shape-shifting maneuvers that make DNA available for whatever purpose it’s needed — whether that is to transcribe proteins, replicate, go to sleep or wake up.
Not long ago, the nuclei of the yeast cells Tsukiyama studies looked like fuzzy dots through his microscope. By contrast, today’s super-resolution microscopy is so sharp, he can see the texture of DNA inside the nucleus. “This was something we could only dream about just a few years ago,” he said. Soon, he predicts, scientists will be able to watch genetic changes in live cells in real time.
Linking their legacy to a trusted organization
Tsukiyama’s research is precisely the type of fundamental discovery David and Deborah Lycette aim to advance — with the ultimate goal of preventing and treating cancer.
The couple, who are retired attorneys, have been involved with Fred Hutch since it was a mere idea. David Lycette joined the Board of Trustees at its very first meeting in January 1972 and served on the board for more than 30 years.
In the early days, the Lycettes hosted dinners at Fred Hutch’s original location to introduce the fledgling center to local business and civic leaders, and lab tours with scientists were the highlight.
“It was marvelous to hear researchers talk about what they were doing and why it was important,” Deborah Lycette said. It still is, she added.
While the Lycettes have stepped back from day-to-day involvement at Fred Hutch, they are avid supporters. When they learned about the Anniversary Challenge — and the goal of matching gifts of $1 million to create 25 new endowed chairs in six areas of scientific focus — they jumped at the opportunity to link their legacy with the organization they have trusted for so long.
“We hope Toshi’s research will result in new information about cancer causes and treatments,” David Lycette said. “Along the line, we know some things you look into won’t work, and that’s important, too.”
Optimism and technology drive progress
As a scientist, Tsukiyama can guarantee that some things won’t work out. “Most principal investigators are unbelievably optimistic,” he said. “We have to be, because 90% of what we do is troubleshooting — an experiment doesn’t work, or equipment fails, or a grant doesn’t get funded. These things happen all the time.”
His innate optimism helps him reframe these setbacks as building blocks for new ideas.
“There are so many questions to be answered,” Tsukiyama said, and the endowed chair will enable him to follow where the science leads.
