Photo: Fred Hutch file
Two of Fred Hutchinson Cancer Research Center’s preeminent researchers tomorrow will be inducted into the Washington Life Science Hall of Fame at the Life Science Innovation Northwest conference in Seattle. The awards recognize the achievements of Hutch President and Director Emeritus Dr. Leland "Lee" Hartwell, who shared the 2001 Nobel Prize in physiology or medicine for discoveries on regulation of the cell cycle; and Dr. Denise Galloway, director of the Hutch’s Pathogen-Associated Malignancies Integrated Research Center, whose research helped pave the way for the HPV vaccine.
Galloway and Hartwell join previous Hutch inductees Dr. E Donnall Thomas and Dottie Thomas, the husband-and-wife research team who pioneered the development of bone marrow transplantation as a cure for blood cancers. Established in 2016, the Washington Life Science Hall of Fame honors “innovative leaders and industry pioneers in Washington state who have made significant contributions to the life sciences.”
The careers of both Hartwell and Galloway highlight the power of basic research and partnerships to drive advances in human health. Hartwell’s work provided insights into how all cancers run amok, while Galloway’s studies on cancer-causing viruses contributed to a cancer-preventive vaccine and lifesaving clinical tests.
Denise Galloway: studying how viruses cause cancer
Human health advances rely on basic research. The HPV vaccine, which protects against the cervical cancer–causing human papillomavirus, has already made enormous impacts on human health — including nearly eliminating cervical cancer in Australia — and it was made possible by basic laboratory studies.
“You never know where the next discovery is going to come from,” said Galloway, who has always done basic research with an eye to human health.
Her own research helped lay the foundation for the cancer-preventive HPV vaccine. Using a key HPV protein, Galloway’s group created vaccine-like particles, in which a single viral protein folds up to look like the real virus. Because virus-like particles can trigger a long-lasting, protective immune response similar to that of real viruses, they can form the basis of a vaccine. The technique Galloway used was pioneered by a researcher working on viruses that infect mice.
The scientist wasn’t interested in vaccines, just virus structure, she said. “It was a basic discovery about how a virus can form that led to the ability to do the same thing with HPV.”
Galloway’s initial focus had not been vaccines, either. After uniting with epidemiologists in Fred Hutch’s Public Health Sciences Division and at the University of Washington, she and her team created the virus-like particles while developing a blood test to assess whether someone who did not currently have detectable HPV had previously ever been infected.
This relationship grew into the Seattle HPV Team, a Fred Hutch and UW collaboration led by Galloway. In 2011, the group received the Team Science Award from the American Association for Cancer Research.
The team showed that nearly every case of cervical cancer arises from HPV infection. They studied how long HPV persists, the immune response to HPV infection, and how many infected people go on to get the disease — all important things to know when designing a vaccine trial. The Seattle HPV team also performed the first proof-of-principle clinical trial showing that, indeed, an HPV vaccine can protect against HPV infection.
Now Galloway focuses on the best way to administer the HPV vaccine. It was first rolled out with a three-dose schedule, but she and her team have shown that two doses are just as effective as three when it comes to stimulating a long-lasting immune response.
She also studies Merkel cell polyomavirus (MCPyV), which can cause Merkel cell carcinoma, or MCC, a rare skin cancer. The link between MCPyV and MCC was only made in 2008, but when she heard of the association, Galloway wasted no time in reaching out to Hutch and UW colleague — and MCC expert — Dr. Paul Nghiem.
Galloway and Nghiem developed a test that can detect MCC recurrence much earlier than standard imaging. It sprang from a scientific whim: Galloway wanted to know whether the MCPyV protein that drives MCC formation triggered a detectable immune response.
It turns out that the protein does trigger an immune response, which falls and rises as tumors shrink and grow. Galloway and Nghiem were able to use immune responses to this single MCPyV protein to help identify which patients might be experiencing a recurrence — and need to undergo imaging — and which patients remained cancer-free and could avoid unnecessary scans.
But there is more to be learned about HPV and MCPyV that could help researchers develop better ways to treat and prevent the infections and their associated cancers, and Galloway intends to learn everything she can. She recently received an Outstanding Investigator Award from the National Cancer Institute to support this work.
Galloway also was appointed director of the recently launched Pathogen-Associated Malignancies Integrated Research Center. The PAM IRC aims to leverage research findings to reduce the worldwide burden of cancers linked to pathogens. The team is exploring partnerships in public and private sectors to bring research advances to the patients who need them.
Photo: Fred Hutch file
Lee Hartwell: yeast studies shed light on cancer
Hartwell won a Nobel Prize for his insights into how cells regulate their growth and division. In order to divide, a cell must copy its DNA, separate its chromosomes (long DNA molecules) and pinch itself into two new cells, each carrying the right amount of DNA. Hartwell discovered that cells have built several “checkpoints” into this process.
Cell cycle checkpoints ensure quality control. Healthy cells can’t move past specific checkpoints if they’ve failed to complete previous steps, such as properly replicating DNA, or evenly parceling chromosomes. Instead, checkpoints force healthy cells to pause and repair damage before proceeding. Unlike normal cells, cancer cells divide wildly — often by finding ways to bypass these very same checkpoints.
Hartwell studied yeast, not human cells. Many biologists at the time expected that untangling the yeast cell cycle would lead nowhere important — certainly not to insights with profound implications for understanding human disease. But Hartwell’s work not only illuminated normal cellular functions, it also helped explain what was occurring in cancer cells that had jettisoned normal function for unfettered growth.
Many scientists have followed up on Hartwell’s insights into the cell cycle to begin developing cancer therapeutics that target cell cycle checkpoints. Several of these therapeutics are showing promise in clinical trials, particularly in breast cancer, melanoma, small-cell lung cancer and head and neck cancer. One cell cycle inhibitor was recently approved, in combination with a standard chemotherapy, as a first-line treatment for a specific type of breast cancer.
Hartwell was also the first to theorize that the many genetic alterations that pile up in cancer cells might leave them reliant on proteins for which healthy cells can compensate. The idea is known as synthetic lethality, and it now forms the basis for drug discovery methods that seek to identify cancer therapeutics that can take down cancer cells while sparing healthy cells. At the Hutch, the approach led to the discovery that certain head and neck tumors rely heavily on a checkpoint protein known as Wee1 (discovered by Dr. Paul Nurse, who shared the Nobel Prize with Hartwell). The discovery led Hutch researchers to open a Phase 1 clinical trial combining a Wee1-targeting drug with standard chemotherapy for head and neck cancer patients.
Though he began his career illuminating the inner workings of yeast cells, Hartwell’s interests quickly expanded. In 1996, shortly before stepping into the role of president and director at Fred Hutch, he helped launch biotech startup Rosetta Inpharmatics to use patterns in gene-expression profiles to identify new targets for cancer drugs. Not long after going public in 2000, Rosetta was acquired by Merck.
During Hartwell’s 13 years as Hutch president, 14 biotech companies sprang from the center's research, several putting down roots in the South Lake Union neighborhood. Hartwell was instrumental in helping position SLU as a biotech hub. Under his leadership, Fred Hutch consolidated its several campuses to one campus in the then-relatively empty SLU area. Since then, many more biotech outfits have sprung up around the lake. Additionally, Hartwell oversaw formation of Fred Hutch's clinical care partner, Seattle Cancer Care Alliance.
As scientists glean more information from normal and diseased cells, Hartwell has turned his attention to harnessing this wealth of information to deliver on the promise of individualized diagnostics and treatments for cancer patients. He currently directs the Pathfinder Center in The Biodesign Institute at Arizona State University, which seeks to promote sustainability education to inspire the next generation of sustainability scientists.
Galloway and Hartwell will be honored at a luncheon tomorrow during Life Science Innovation Northwest.