Zena Werb

University of California, San Francisco

Election Year: 2010
Primary Section: 42, Medical Physiology and Metabolism
Secondary Section: 22, Cellular and Developmental Biology
Membership Type: Member

Research Interests

As a cell biologist, I have been interested in elucidating the molecular and cellular bases of the extracellular microenvironment of cells and tissues and their roles in the normal functioning and pathogenesis. My approach was to use normal development and tissue repair paradigms to give insights into processes such as tumorigenesis. Starting with my discovery that fibroblasts were a source of matrix metalloproteinases (MMPs), we learned that MMPs required activation by a proteinase cascade, a fundamental process in vivo. We then linked the cytoskeleton to ECM through integrins and discovered that integrins signal. A recurring research theme has been the biology and function of inflammatory cells. The two themes came together when we discovered that macrophages were important sources of MMPs that functioned in vivo for healing wounds and angiogenesis. Concentrating on the role of MMPs in development and cancer, we discovered that recruitment of inflammatory cells was the key event in the angiogenic switch, which precedes progression to invasive tumors. This compelling evidence that innate inflammatory cells contribute to tumorigenesis fostered a paradigm shift to highlight the central importance of the cellular microenvironment in normal development and in the progression of tumors, which we are still studying

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