Zena Werb, PhD, was born in 1945 to Polish-Jewish parents in the Nazi concentration camp at Bergen-Belsen in Germany. After being freed from the camp at the end of the war, Werb’s mother carried her across the Alps to reunite with her father in Italy. From there, the family emigrated to Canada as refugees, settling first in Saskatchewan, and then on a farm in Ontario. Werb showed a passion for math and science from a young age, an interest encouraged by her father. As a student at the University of Toronto, Werb was attracted to geology, but ultimately chose to study biochemistry instead, after learning women could not participate in critical summer fieldwork in geology.

As a graduate student with Zanvil A. Cohn, MD, at Rockefeller University, Werb’s research demonstrated a new role for the immune system’s macrophage cells in helping cells to eliminate excess cholesterol. This work led to an abiding interest in how cells and proteins communicate. Later, as a postdoctoral researcher at Strangeways Research Laboratory in Cambridge, England, Werb studied fibroblasts, collagen-producing cells responsible for building the extracellular matrix (ECM) that holds together all our tissues. Werb’s research revealed that fibroblasts also produce enzymes called matrix metalloproteases (MMPs), which can take the extracellular matrix apart.

After a brief stint at Dartmouth Medical School, Werb took a faculty position at UCSF in 1976 and has been at the University ever since, eventually becoming vice-chair of the Department of Anatomy, a position in which she served for many years. At UCSF, Werb’s continued interest in interactions between cells and proteins led to the fundamental discovery that the ECM is not just a passive scaffold for our tissues, but also communicates directly with cells via intermediary proteins called integrins. Her lab also showed that MMPs’ ability to reshape the ECM gave these little-studied molecules important roles in biological functions as diverse as embryonic implantation, development, and blood-vessel formation.

These discoveries led to seminal work in the 1980s with Mina Bissell, PhD, at Lawrence Berkeley National Laboratory, which revealed that some MMPs can promote tumor formation and play a role in metastasis by releasing tumors from the constraints of the ECM. “These insights led a lot of people to try to develop MMP inhibitors to fight cancer, but Zena argued that the biology was more complicated: some MMPs would likely promote cancer while others would protect against malignancy,” Weaver said. “This didn’t make her very popular in some quarters, but Zena understood that cancer is complex, a consequence of the beautiful orchestration of tissue development gone awry. When MMP inhibitors failed, it hurt Zena’s ability to get funding and high-level publications in this area. But she wasn’t one to be daunted – she just carried on and continued doing the work.”

Werb’s early interest in the immune system also came full circle in a long-standing collaboration with Lisa Coussens, PhD, at Oregon Health and Science University beginning in the 1990s, which identified inflammation as a key feature of cancer. Another indicator of the importance of the tumor “microenvironment” on cancer outcomes, this work has helped inform the recent development of cancer immunotherapies.

Werb’s work has continued to focus on understanding breast cancer metastasis in the context of normal breast development and cancer’s local environment, including developing new approaches to identifying metastatic cancers and potentially halting their spread. Werb showed clear parallels between how the innate immune system regulates the growth of the mammary glands during adolescence and how these immune cells contribute to either inhibiting or promoting breast cancer malignancy, which Werb saw as a kind of perversion of normal development.

Werb’s foundational work on MMPs, the extracellular matrix, mammary gland development, and breast cancer has made her one of the most cited researchers in the world, and has led to numerous awards and honors, including membership in the National Academy of Sciences’ Institute of Medicine and past presidency of the American Society of Cell Biology. Werb was also an elected Fellow of the American Association of Cancer Research, of the American Society for Cell Biology, and the American Academy of Arts and Sciences. She was a recipient of the E.B. Wilson Medal from the American Society for Cell Biology, and a Lifetime Achievement Award from Women in Cell Biology, an ASCB subgroup.