Joe Gray | Seeing molecules and mechanisms
Joe Gray has a very personal motivation for advancing cancer research. When he was 24, he lost his father to lung cancer. Later his wife developed breast cancer, and both he and his son have had skin cancer. “I’ve dealt with the disease firsthand,” he says. “I’ve seen the limitations of current treatments. That gap in our knowledge has a profound effect on people’s lives.”
Today, Gray is creating what he calls the “Google Earth” view of cancer cells and tissues: a way of zooming in and out on the disease in the body. “We want to be able to see, at a higher level, how the tissues are organized,” the biomechanical engineer explains, “and at a lower level how the cells are organized, and at a lower level still, how molecular complexes that make up cells are organized—and how all of this works together.” To that end, his new lab will house as many as six high-powered electron microscopes built by Hillsboro’s FEI, the industry leader. One, the Titan Krios, sells for as much as $6 million depending on how it’s configured; in 2010, scientists at UCLA used the same model to capture images of individual atoms in a frozen virus, a feat previously considered impossible. FEI is both footing part of the bill for the necessary instruments and planning to embed its own scientists in Gray’s lab. The instruments include electron microscopes so powerful, they allow researchers to see individual genes on cancer cells, as well as a groundbreaking model that lets scientists switch between big-picture views—a bunch of cancer cells, for example—and even more infinitesimally small features, like chromosomes within one of those cells.
As a pioneer in the imaging of very small things—he developed microscope techniques now widely used to detect breast cancer mutations—Gray aims to usher in a new understanding of cancer’s basic workings. “We need to understand how cancer cells function, how they grow, how they die, how they move, how they make new blood vessels,” he says. To do this, Gray and his colleagues will observe cancerous cells in various locations throughout the body in a way that no one has been able to do before.
“It’s the difference between seeing the parts and seeing the parts all working together,” Druker says.
Just as astronomers stitch together composite views of the sky with different types of telescopes, Gray says his microscopes will together make possible a picture of how genomic abnormalities drive different cancers in individual patients. “I think it’s going to be very clear that cancer differs from person to person,” he says, “and that’s going to have a fundamental impact on how the individual cancer patient will respond.”
Lisa Coussens | Rewiring rogue immune cells
“It took about one second,” says Lisa Coussens about convincing the researchers in her lab at the University of California–San Francisco to make the move with her to OHSU late last year. Three of them jumped at the chance to work with Druker, whose goal is to turn lab results into treatments for living, breathing human beings.
“Brian has assembled a team of people that think about that path and what’s needed,” she says, “and not only from an ‘interesting science’ point of view.” In addition to those specialists, her deal with OHSU also provides funding to hire 10 cancer biologists. Each of their labs will have 10 to 15 people working within them. “It’s a tremendous boon to the scientific community,” she says, “but also a tremendous boon to the Portland economy.”
Coussens has spent the past 20 years battling cancer’s most insidious move: hijacking the body’s immune system. Ordinarily, immune cells help to maintain tissue and organ health and ward off infections. “Clearly without them we’d be a mess,” Coussens says. Tumors, however, take advantage of immune cells’ protection to thwart normal cell death and boost their own abnormal growth. Researchers still don’t know exactly how all this works. But Coussens recently discovered that when she used targeted drugs to eliminate compromised immune cells in and around tumors in lab mice, the cancer cells became more vulnerable to chemo and radiation. What’s more, when she eliminated the co-opted immune cells, healthy immune cells stepped in and did their job, killing off malignant growths.
In hot pursuit of these insights, Coussens is now overseeing the first-ever human trial to combine chemotherapy with a drug that targets rogue immune cells.
Eventually, Coussens wants to reprogram these compromised immune cells to make them keep tumors in check rather than helping them to grow. Immune cells also appear to help tumors get oxygen and nutrients, in ways not yet understood. Thus, changing how such cells function could put cancer in a double bind. As Coussens puts it: “One rock, two birds.”