52 THE SCIENTIST | the-scientist.com
PROFILEShe did, however, initially face challenges in growing her
income. Around a year and a half after Werb arrived at the
university, the director of the radiobiology lab, Harvey Patt, was
diagnosed with an aggressive form of cancer and passed aw ay. The
person who took his place “was another male chauvinist,” Werb
recalls. “He’d give the male junior faculty increases in salary, but
when I [asked] he said, ‘Oh, we don’t have the money.’”But Werb never let herself be discouraged. “I’ve always been
someone who, when things don’t work out, I remember them,
but I don’t dwell on them,” Werb says. “I look for how to go
beyond that.” Eventually, Werb received a cross-appointment in
the anatomy department—where she was treated equitably—and
moved there full-time after the radiobiology lab lost its funding.MICROENVIRONMENT AND MENTORSHIP
As she continued her work on MMPs, Werb and her colleagues
revealed that the enzymes were critical regulators of the
extracellular microenvironment. As such, the researchers learned,
MMPs participate in a variety of processes, including developmentand cancer. “She has done seminal work in the area of the tumor
microenvironment,” says Rakesh Jain, a cancer biologist at
Massachusetts General Hospital. “Breast cancer is where she
focused most of her research, and her work is just phenomenal.”
Werb collaborated with Mina Bissell at the Lawrence Berkeley
National Laboratory for much of her early work on breast cancer.
When the pair met in the 1980s, Bissell’s lab was investigating
the roles different proteins and hormones played in mammary
glands. Together, Werb’s and Bissell’s labs demonstrated that not
only were MMPs expressed in cancer, but that the overproduction
of these enzymes could promote tumor formation and drive
malignancy (Cell, 98:137–46, 1999).
Another of Werb’s key scientific contributions was linking
inflammation to cancer. She conducted several of the early studies
in this area with Lisa Coussens, a cancer biologist at Oregon
Health & Science University. Werb met the young researcher in
the 1990s, when Coussens was a postdoc in biologist Douglas
Hanahan’s lab at UCSF. Due to Coussens’s interest in immune
cells, she ended up working closely with Werb. Their work laid the
foundation for establishing inflammation as a hallmark of cancer.
A review that Werb and Coussens coauthored has been cited more
than 10,000 times (Nature, 420:860–7, 2002).Coussens says that the direction of her career can be traced to
her collaboration with Werb. “It was really Zena’s encouragement
that led me into studying early inflammation,” Coussens says.
“She’s been the most profoundly influencing senior scientist that
I’ve had as a mentor in my life.”
Coussens is not alone. Over the years, Werb has mentored
countless budding scientists. “She birthed an entire generation
of [researchers],” Coussens tells The Scientist. “Many of us lead
in our fields, but none of us could have done that without Zena.”
Andrew Ewald, a cell biologist at Johns Hopkins University
and one of Werb’s former postdocs, says that grad students and
senior faculty alike often sought Werb’s guidance. “She was open
to any idea... [but] also very critical,” Ewald adds. “Her advice
was treasured by a huge range of people... because she’d tell you
whether you had a good idea or a bad one.”
Now in her 70s, Werb continues to be actively involved in
research and is trying to determine why only some tumors end up
metastasizing, even though all cancers have the potential to. One
reason, she and colleagues recently reported, might be because
some components of the innate immune system can actually
prevent cancer’s spread. “There’s something generic or universal
about the problem [of metastasis],” Werb says, “and I want to
understand it.” gShe has done seminal work in the area of the
tumor microenvironment.... Breast cancer is
where she focused most of her research, and
her work is just phenomenal.
—Rakesh Jain, Massachusetts General HospitalVICKI PLAKS; PETER DIJKGRAAF; BRYAN WELMMAMMARY MATRIX: To learn how cancer develops in the mammary glands
of mice, Werb has studied hyperplasia in MMTV-neu tumors (top), the
growth of epithelial cells (marked with GFP or RFP, lower left), and how the
overproduction of matrix metalloproteinase-3 affects the tissue (lower right).