FEATURE — Spring 2009
   

 
(Photo: David Kilper)

To Control Cancer’s Spread
Medical Professor Helen Piwnica-Worms’ discoveries on how cells divide and pass on genetic material are proving central to cancer research. Colleagues are now testing ways to stop damaged cells from dividing.

by Janni L. Simner

Helen Piwnica-Worms cares passionately about science—and has since being a child. “Most little girls go to the store with their mother hoping to get a doll or candy,” she says, “but I asked for a science book every time.” Even so, it wasn’t until she reached graduate school that Piwnica-Worms realized she wanted to be a scientist.

“Growing up, I never knew any female scientists, so I thought I’d be a teacher,” she explains. Yet the nagging feeling that she hadn’t learned enough led her to more and more advanced studies. Finally, she entered graduate school in biomedicine. “When I conducted my first laboratory experiment—coming up with a hypothesis, testing it, and getting an answer—it was an endorphin-releasing experience,” Piwnica-Worms says. And she’s been hooked on research ever since.

As the Gerty T. Cori Professor of Cell Biology and Physiology in the School of Medicine, Piwnica-Worms uses her passion for research to answer fundamental questions about how cells divide—and about why they sometimes don’t stop dividing. Her work may one day provide valuable new tools for fighting cancer and other diseases. “Helen is a leader in cell cycle work at a very basic level, and she’s well-known internationally for her work,” says Philip Stahl, the Edward C. Mallinckrodt, Jr. Professor and head of the Department of Cell Biology and Physiology. “She’s also one of a few select scientists who can navigate between basic science and translational research.”

Helen Piwnica-Worms, the Gerty T. Cori Professor, is an expert in cell cycle controls and cancer cell proliferation. In her lab, she collaborates with many researchers, including Yuchi Honaker, a sixth-year doctoral student studying molecular cell biology. (Photo: David Kilper)

Piwnica-Worms has spent the last two decades studying the complex biochemical processes by which cells—the building blocks of nearly all living things—divide and pass on their genetic material. As a result, she’s discovered an important checkpoint moment where the cell stops, takes stock, and examines its DNA before giving the “all clear” for cell division to proceed.

When a dividing cell detects damage at a checkpoint, Piwnica-Worms says, that “all clear” signal never comes. Instead, the cell activates a protein called CHK1 (pronounced “check one”). CHK1 acts to get rid of another molecule in the cell, the CDC25A phosphatase. Since CDC25A is required for cells to divide, by removing it, CHK1 effectively stops division from taking place—and keeps damaged DNA from being passed on to daughter cells. When the checkpoint process breaks down, however, and cells fail to put the brakes on cell division, diseases such as cancer can result.

Because of these findings, Piwnica-Worms’ work shifted into the clinic, where colleagues now test ways to use CHK1 inhibitors to stop damaged cells from dividing—and thus control cancer’s spread. Preliminary clinical trials show particularly promising results with triple negative breast cancer—the disease’s progress has been slowed—and further trials are currently under way.

“It’s very exciting to take basic science from the laboratory into clinical trials, and to potentially be able to do some good,” Piwnica-Worms says. “That makes me want to get up and come to work every day.”

Piwnica-Worms is quick to emphasize, however, that her research—and science in general—is valuable for more than its clinical applications. She remains committed to the importance of scientific inquiry as an end in itself, and she points out that Nobel Prize–winning biochemist Gerty T. Cori, for whom her professorship is named, was a basic scientist as well. “It’s vital to understand how significant basic research is,” Piwnica-Worms says. “You have to let scientists ask important questions. That’s the base of the pyramid upon which scientific progress builds.”

She adds that no one can determine what research will have clinical applications down the road. “I had an interest in understanding what drives cells to divide,” she says. “That this now has clinical relevance is the icing on the cake. But it’s not why I did it. I love the basic mechanistic understanding of the science. Ultimately, I feel it all will be relevant at some point.”

Piwnica-Worms’ University colleagues agree that her research is top-notch. “She’s a tenacious and focused researcher,” says Andrey Shaw, the Emil R. Unanue Professor of Immunobiology and a sometime collaborator with Piwnica-Worms. “She has extremely high standards, asks tough questions, and is a very clear thinker.”

After earning a Ph.D. in microbiology from Duke University, Piwnica-Worms and her husband, David Piwnica-Worms (who is now professor of radiology and developmental biology at the University’s Mallinckrodt Institute of Radiology), initially moved to Boston, where Helen Piwnica-Worms did her postdoctoral work at the Dana-Farber Cancer Institute. She accepted her first faculty position at the Tufts University School of Medicine and then moved to Harvard Medical School a few years later. She and her husband originally planned to remain in Boston, but in 1994 Washington University’s Department of Cell Biology and Physiology contacted Helen Piwnica-Worms, looking for a faculty member with expertise in cell cycle control.

“My husband and I had a great appreciation for the Midwest and what it could offer, especially in terms of family life and raising children,” Piwnica-Worms says. When she was deemed the top candidate for the cell biology position, and when her husband was also offered a position at the Mallinckrodt Institute, they both accepted and moved to St. Louis with their young son and daughter. Those children are now themselves college students, and their daughter is a senior in Washington University’s College of Arts & Sciences, studying pre-med and English literature.

Piwnica-Worms says she loves the University’s atmosphere, which encourages collaboration among researchers. “No matter where your science takes you here, there’s always someone with expertise who can help you,” she says. “It’s imperative for researchers to interact. Science is becoming so complex that one laboratory can’t have all the technology necessary to solve a problem.”

“It’s imperative for researchers to interact. Science is becoming so complex that one laboratory can’t have all the technology necessary to solve a problem,” says Piwnica-Worms.

 

“It’s great fun to collaborate with her, because she truly loves and is enthusiastic about science,” Shaw says, adding that Piwnica-Worms is generous with her time and expertise. “Colleagues like Helen are what make Washington U. such a great environment in which to do science.”

Piwnica-Worms actively encourages collaboration among departments through her work at the Siteman Cancer Center, where she oversees the cell proliferation program. In that role, she runs a seminar series that invites students and faculty throughout the University to meet and share their cell-cycle-related research.

In her own department, Piwnica-Worms gives several lectures each year on cell cycle control and cell proliferation. She also mentors graduate students and postdoctoral researchers in her lab, where she enjoys watching students get the same endorphin rush she experienced as a young researcher. “They’ll come running into my office to show me something, and that’s so exciting,” she says. “It’s very rewarding to work with students and to see them develop into young scientists ready to launch out on their own.”

She advises young people considering a science career to follow their passions as she did. “If you feel that endorphin release when you do an experiment, then I’d say this is the profession for you. Follow your heart and follow your biological questions, and the rest will all fall into place.”

Piwnica-Worms repeatedly has been recognized, nationally and internationally, for her work. She’s a Howard Hughes Medical Institute Investigator and a Fellow of the American Association for the Advancement of Science. She’s received a Spirit of Health Award for Cancer Research from the American Cancer Society and was elected to the board of directors of the American Association for Cancer Research. In 2007, she received the Carl and Gerty Cori Faculty Achievement Award from Washington U., and in 2008, she was named the University’s first Gerty T. Cori Professor.

The endowed professorship is part of the University’s BioMed 21 initiative, which was created to encourage the use of research discoveries to diagnose and treat patients. “She is a national leader in research, a terrific teacher, a leader in developing the careers of young scientists, and a wonderful colleague,” Stahl says.

Piwnica-Worms looks forward to continuing to understand cell cycle control and cell machinery in the decades ahead. She hopes to bring her work—much of which has been done on strains of cells cultured in the lab—to whole organisms. New noninvasive imaging techniques are making it easier to work with animals, and, along the way, those techniques have brought Piwnica-Worms a new collaborator: She now works with her husband at the Mallinckrodt Institute. “That’s really been a lot of fun,” she says, adding that it’s the first time their work is overlapping.

Wherever her future work takes her, Piwnica-Worms says her focus on fundamental research will remain. “I’ll always be interested in the basic mechanisms of cell cycles and how they’re turned on and off,” she says. “We still have a lot to learn.”

Janni L. Simner, A.B. ’89, A.B. ’89, is a freelance writer based in Tucson, Arizona.