Zena Werb, Ph.D.
Professor and Vice Chair, Department of Anatomy
University of California, San Francisco
513 Parnassus Avenue
HSW 1321, Box 0452,
San Francisco, CA 94143-0452
Tel: (415) 476-4622
Fax: (415) 476-0616
Cell-cell and cell-extracellular matrix (ECM) interactions provide cells with information essential for controlling morphogenesis, cell-specific fate determination, gain or loss of tissue-specific functions, cell migrations, tissue repair and cell death. Cleavage of cell surface and ECM proteins by matrix metalloproteinases and other proteolytic enzymes initiate rapid and irreversible signal transduction events that lead to altered cell behavior. The consequences of these signals are morphogenesis, cell migration, physiologic tissue remodeling or pathologic processes.
Our laboratory uses functional genomic approaches to define the role of proteolysis in controlling cell fate decisions, cell survival, vasculogenesis and angiogenesis during development and tumorigenesis. Matrix metalloproteinases play a critical role by regulating extracellular matrix and cell surface proteins, growth and angiogenic factors, cell recruitment, cell proliferation and apoptosis. We wish to determine the identity and function of the critical proteinases, how their expression and activities are regulated, what the molecular and cellular targets of the proteinases are, and how these regulate the signaling pathways.
We are studying several critical developmental processes: endochondral bone formation, placental morphogenesis, adipogenesis and branching morphogenesis in the mammary gland and lung. We are also studying the mechanisms underlying epithelial-mesenchymal communication. We are taking genetic and molecular approaches to understand what proteinases are critical cell surface molecules, and how they regulate EGF, VEGF, hedgehog and FGF receptor signaling.
Proteinases are universally upregulated during tumor progression. We are using genetic approaches to understand what role they play during initiation, progression, malignant conversion, angiogenesis and metastasis. We wish to elucidate how proteinases regulate the cellular microenvironment and what role they play in altering the host stroma and the recruitment and function of inflammatory cells and endothelial cells.
University of Toronto, Toronto, Canada, B.Sc., 1966, Biochemistry
Rockefeller University, New York, NY, Ph.D., 1971, Cell Biology
Strangeways Research. Laboratory, Cambridge, U.K., Postdoc., 1971-73, Protein Chemistry
Primary Research Interest: Developmental and Stem Cell Biology
Secondary Research Interest: Cancer Biology and Cell Signaling
Functions of the Extracellular Microenvironment in Development and Cancer