50 THE SCIENTIST | the-scientist.com
PROFILEHUGO GONZALEZW
hen no one in Zena Werb’s University of California,
San Francisco lab wanted to investigate whether ele-
ments of the three-dimensional web of macromole-
cules surrounding cells could communicate with those cells, she
decided to do the experiment herself.
It was the 1980s, a time when scientists saw this web,
called the extracellular matrix (ECM), as primarily a support
structure for cells. But Werb’s study showed that proteins
within the matrix are involved in signaling. Specifically, she
discovered that integrins, transmembrane molecules that help
adhere a cell to its surroundings, not only bind but respond to
ECM proteins, activating intracellular signaling pathways—
regulating, for example, the expression of genes that encode
ECM-degrading enzymes called matrix metalloproteinases
(MMPs). The extracellular matrix was more than just a scaffold,
Werb realized—a concept that became central to much of her
subsequent work.
Over the past few decades, Werb, a cell and molecular
biologist, has shown that the extracellular matrix is a dynamic
network that greatly influences health and disease. Related to
that idea, she has contributed numerous noteworthy discoveries,
including the role of MMPs in embryonic implantation, early
development, and metastasis. Her work has revealed that cells’
surroundings are important to their well-being.FROM NAZI GERMANY TO NEW YORK CITY
Werb was born to Jewish refugee parents during World War II in
March 1945. Her parents had been split up before she was born,
so when her mother was able to return to their native Poland
a month after Werb’s birth, she tried to reach Werb’s father,
with whom her mother had lost contact. When Werb’s mother
discovered Werb’s father was in Italy, she immediately made plans
to join him.
It would be half a year before Werb’s family reunited. To reach
Italy, Werb’s mother traveled with her infant both by train and on
foot, with very little money. Reaching Austria, she hit a roadblock:
Italy would not allow refugees across its border. With the help of a
guide who led her on a pathway through the Alps, Werb’s mother
managed to sneak into the country with her daughter, eventually
locating Werb’s father. The reunited family spent six months in
a displaced persons camp in northern Italy before immigrating
to Canada in 1948.
After a year in the prairie province of Saskatchewan, the
family settled in southern Ontario, where Werb’s parents boughta farm that they worked while she attended classes in a small, one-
room rural schoolhouse. “We had terrible teachers,” Werb recalls.
But her father was passionate about math and physics, which he
had studied back in Europe. “So by the age of four,” she says, “I
had learned Newton’s laws.”
Under her father’s influence, Werb’s interest in science grew,
and she went on to pursue a bachelor’s degree at the University of
Toronto. She initially developed a strong interest in geology, and
was eager to join a field course investigating geological phenomena
in the Rocky Mountains. “Since I was the top student in the class,
it should have been no problem getting into it,” Werb says. “But I
couldn’t because they didn’t [have] any facilities for women.”
The experience taught Werb a valuable lesson: “it was obvious to
me that I didn’t have a future in this area,” she says. She shifted gears
and spent the next few years studying biochemistry and biophysics,
developing a passion for those subjects that led her to a doctoral
program at Rockefeller University in New York City in 1966.THE INNER AND OUTER LIVES OF CELLS
Werb was drawn to Rockefeller in part because of the opportunity
to work on X-ray crystallography with Gerald Edelman, the
scientist who had uncovered the structure of antibody molecules.
But when she rotated through his lab, “I found out that he was
an impossible person,” Werb recalls. Taking the advice of one of
Edelman’s former students, she went to work with biologist Zanvil
Cohn, whose research focused on macrophages, massive immune
cells that stretch out and engulf foreign cells and debris. In Cohn’s
lab, Werb saw live macrophages under a microscope for the first
time. After that, “I was hooked on cell biology,” she says.
Cohn was her most important mentor, Werb says. He believed
in letting his students be independent and allowed Werb to
freely pursue the scientific questions of her choice. “We talked,
but he allowed me to be the driver [of my research].” With that
academic freedom, she conducted experiments with macrophages
that revealed the crucial role they play in regulating cholesterol
metabolism (J Exp Med, 135:21–44, 1972).
As a natural extension of this work, Werb wanted to
experiment with lipoproteins, soluble proteins that combine
with and transport fats through the circulatory system. However,
due to the technical challenges associated with obtaining and
isolating the molecules from blood, lipoproteins were hard to
come by at the time—and Werb wasn’t getting much help from
the university’s faculty. The atherosclerosis expert at Rockefeller
would only take an appointment with Werb’s thesis advisor, whoUCSF cell and molecular biologist Zena Werb unveiled a role for the breakdown of proteins
in the extracellular matrix in both healthy and pathogenic cells.BY DIANA KWONExploring the Matrix