University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Zena Werb, PhD

Zena Werb, PhD

Professor and Vice-Chair, Department of Anatomy, UCSF; Associate Director for Basic Science, UCSF Helen Diller Family Comprehensive Cancer Center

Cancer Center Program Memberships

Cancer Immunology

Research Summary

I have led projects on breast cancer and the environment, concentrating on puberty as the window of susceptibility for the past 12 years. My expertise in breast development, breast cancer, and the epithelial microenvironment has been developed over three decades. I have concentrated on the molecular mechanisms involved in extracellular matrix remodeling and inflammatory cell function in mammary development and breast cancer. We have developed and used a variety of new technologies and models ranging from molecular biology to genetically engineered mouse models to intravital microscopy and 3D culture models. We have published over 450 scientific papers.

My major interest is in driving the field of the extracellular microenvironment in development, inflammation, fibrosis, and tumor biology forward technically and conceptually. Another goal is to determine insights from mammary development that help explain breast stem cells, and susceptibility to cancer development and metastasis. My research program has been characterized by innovation and thoroughness. I have considerable experience in administering projects with collaborations and co-authored publications. I have also put considerable effort into mentoring young scientists and have trained more than 70 students and postdoctoral fellows.

Education

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


Professional Experience

  • 1973-1975
    Research Scientist, Strangeways Res. Lab., Cambridge, U.K.
  • 1975-1976
    Visiting Assistant Professor of Medicine, Dartmouth Medical School, Hanover, NH
  • 1976-1980
    Asst. Professor of Radiobiology, Radiology, Univ. of California, San Francisco
  • 1979-1980
    Asst. Professor of Anatomy, UCSF
  • 1980-1983
    Assoc. Professor of Anatomy and Radiology, UCSF
  • 1983-present
    Professor of Anatomy, UCSF
  • 1985-1986
    Visiting Prof. (Lab. of N.J. Proudfoot), Sir William Dunn School of Pathology, Univ. of Oxford, U.K.
  • 1998
    Visiting Professor, Institut Curie Paris
  • 1999-present
    Vice-chair, Dept of Anatomy, UCSF
  • 2006-2007
    Visiting Professor, Max-Planck Institute for Biochemistry, Martinsried, Germany

Honors & Awards

  • 1971-1973
    Fellow, Medical Research Council of Canada
  • 1982
    R.R. Bensley Memorial Lecturer of the American Association of Anatomists
  • 1985-1986
    Fellow, John Simon Guggenheim Foundation
  • 1986
    Muriel Trotter Lecturer, Washington University, St. Louis
  • 1993-1994
    Sigma Xi National Lecturer
  • 1996
    FASEB Excellence in Science Award
  • 1997
    Chitra Biswas Memorial Lecturer, Tufts Medical School
  • 1998
    Rothschild/Mayent Fellowship, Institut Curie, Paris
  • 1998
    Earl Benditt Distinguished Lecturer, University of Washington
  • 1999
    J.L. Melnick Lecturer, Baylor College of Medicine
  • 1999
    Biosciences Distinguished Lecturer, Lawrence Berkeley National Laboratory
  • 2000
    Gwendolyn J. Stewart Award, Temple University
  • 2001
    Charlotte Friend Lecturer, AACR
  • 2001
    44th Faculty Research Lecturer, UCSF
  • 2001
    H.B. Parker Lecture, Pacific Northwest National Laboratory
  • 2002
    Elected Member, Institute of Medicine
  • 2003
    Elected Fellow, American Academy of Arts and Sciences
  • 2003
    Doctor of Medicine (honoris causa), University of Copenhagen
  • 2004
    Schlessinger Lecture, Beth Israel Deaconess Medical Center, Harvard Medical School
  • 2004
    A. S. Wiener Lecture, New York Blood Center
  • 2005
    Maud L. Menten Lecturer, University of Pittsburgh
  • 2006
    Alexander von Humboldt Research Award
  • 2007
    E.B. Wilson Medal, American Society for Cell Biology
  • 2009
    Colin Thomson Memorial Medal, Association for International Cancer Research
  • 2010
    Elected Member, National Academy of Sciences
  • 2010
    American Society for Cell Biology, Women in Cell Biology Senior Award
  • 2011
    Zero Breast Cancer 2011 Community Breast Cancer Research Award

Selected Publications

  1. Medler TR, Murugan D, Horton W, Kumar S, Cotechini T, Forsyth AM, Leyshock P, Leitenberger JJ, Kulesz-Martin M, Margolin AA, Werb Z, Coussens LM. Complement C5a Fosters Squamous Carcinogenesis and Limits T Cell Response to Chemotherapy. Cancer Cell. 2018 Oct 08; 34(4):561-578.e6.
    View on PubMed
  2. Gonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 2018 Oct 01; 32(19-20):1267-1284.
    View on PubMed
  3. Nguyen QH, Pervolarakis N, Blake K, Ma D, Davis RT, James N, Phung AT, Willey E, Kumar R, Jabart E, Driver I, Rock J, Goga A, Khan SA, Lawson DA, Werb Z, Kessenbrock K. Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity. Nat Commun. 2018 May 23; 9(1):2028.
    View on PubMed
  4. Takai K, Drain AP, Lawson DA, Littlepage LE, Karpuj M, Kessenbrock K, Le A, Inoue K, Weaver VM, Werb Z. Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers. Genes Dev. 2018 Feb 01; 32(3-4):244-257.
    View on PubMed
  5. Devignes CS, Aslan Y, Brenot A, Devillers A, Schepers K, Fabre S, Chou J, Casbon AJ, Werb Z, Provot S. HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice. Proc Natl Acad Sci U S A. 2018 Jan 16.
    View on PubMed
  6. Sun Z, Wang CY, Lawson DA, Kwek S, Velozo HG, Owyong M, Lai MD, Fong L, Wilson M, Su H, Werb Z, Cooke DL. Single-cell RNA sequencing reveals gene expression signatures of breast cancer-associated endothelial cells. Oncotarget. 2018 Feb 16; 9(13):10945-10961.
    View on PubMed
  7. Gonzalez H, Robles I, Werb Z. Innate and acquired immune surveillance in the postdissemination phase of metastasis. FEBS J. 2018 Feb; 285(4):654-664.
    View on PubMed
  8. Cooke DL, McCoy DB, Halbach VV, Hetts SW, Amans MR, Dowd CF, Higashida RT, Lawson D, Nelson J, Wang CY, Kim H, Werb Z, McCulloch C, Hashimoto T, Su H, Sun Z. Endovascular Biopsy: In Vivo Cerebral Aneurysm Endothelial Cell Sampling and Gene Expression Analysis. Transl Stroke Res. 2018 Feb; 9(1):20-33.
    View on PubMed
  9. Kessenbrock K, Smith P, Steenbeek SC, Pervolarakis N, Kumar R, Minami Y, Goga A, Hinck L, Werb Z. Diverse regulation of mammary epithelial growth and branching morphogenesis through noncanonical Wnt signaling. Proc Natl Acad Sci U S A. 2017 03 21; 114(12):3121-3126.
    View on PubMed
  10. Shahi P, Wang CY, Lawson DA, Slorach EM, Lu A, Yu Y, Lai MD, Gonzalez Velozo H, Werb Z. ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression. Proc Natl Acad Sci U S A. 2017 03 21; 114(12):3169-3174.
    View on PubMed
  11. Takai K, Le A, Weaver VM, Werb Z. Targeting the cancer-associated fibroblasts as a treatment in triple-negative breast cancer. Oncotarget. 2016 Dec 13; 7(50):82889-82901.
    View on PubMed
  12. Wang CY, Shahi P, Huang JT, Phan NN, Sun Z, Lin YC, Lai MD, Werb Z. Systematic analysis of the achaete-scute complex-like gene signature in clinical cancer patients. Mol Clin Oncol. 2017 Jan; 6(1):7-18.
    View on PubMed
  13. Horiuchi D, Camarda R, Zhou AY, Yau C, Momcilovic O, Balakrishnan S, Corella AN, Eyob H, Kessenbrock K, Lawson DA, Marsh LA, Anderton BN, Rohrberg J, Kunder R, Bazarov AV, Yaswen P, McManus MT, Rugo HS, Werb Z, Goga A. PIM1 kinase inhibition as a targeted therapy against triple-negative breast tumors with elevated MYC expression. Nat Med. 2016 11; 22(11):1321-1329.
    View on PubMed
  14. Allaoui R, Bergenfelz C, Mohlin S, Hagerling C, Salari K, Werb Z, Anderson RL, Ethier SP, Jirström K, Påhlman S, Bexell D, Tahin B, Johansson ME, Larsson C, Leandersson K. Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers. Nat Commun. 2016 Oct 11; 7:13050.
    View on PubMed
  15. Koledova Z, Zhang X, Streuli C, Clarke RB, Klein OD, Werb Z, Lu P. SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling. Proc Natl Acad Sci U S A. 2016 09 27; 113(39):E5731-40.
    View on PubMed
  16. Trivedi A, Zhang H, Ekeledo A, Lee S, Werb Z, Plant GW, Noble-Haeusslein LJ. Deficiency in matrix metalloproteinase-2 results in long-term vascular instability and regression in the injured mouse spinal cord. Exp Neurol. 2016 Oct; 284(Pt A):50-62.
    View on PubMed
  17. Chou J, Chan MF, Werb Z. Metalloproteinases: a Functional Pathway for Myeloid Cells. Microbiol Spectr. 2016 04; 4(2).
    View on PubMed
  18. Hagerling C, Werb Z. Neutrophils: Critical components in experimental animal models of cancer. Semin Immunol. 2016 04; 28(2):197-204.
    View on PubMed
  19. Williams KE, Lemieux GA, Hassis ME, Olshen AB, Fisher SJ, Werb Z. Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals. Proc Natl Acad Sci U S A. 2016 Mar 08; 113(10):E1343-51.
    View on PubMed
  20. Lawson DA, Werb Z, Zong Y, Goldstein AS. The Cleared Mammary Fat Pad Transplantation Assay for Mammary Epithelial Organogenesis. Cold Spring Harb Protoc. 2015 Dec 02; 2015(12):pdb.prot078071.
    View on PubMed

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