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

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

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
  • 2018
    AACR Distinguished Lectureship in Breast Cancer Research
  • 2019
    2019 Fellow of the AACR Academy

Selected Publications

  1. Hagerling C, Owyong M, Sitarama V, Wang CY, Lin C, van den Bijgaart RJE, Koopman CD, Brenot A, Nanjaraj A, Wärnberg F, Jirström K, Klein OD, Werb Z, Plaks V. LGR5 in breast cancer and ductal carcinoma in situ: a diagnostic and prognostic biomarker and a therapeutic target. BMC Cancer. 2020 Jun 10; 20(1):542.
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  2. Davis RT, Blake K, Ma D, Gabra MBI, Hernandez GA, Phung AT, Yang Y, Maurer D, Lefebvre AEYT, Alshetaiwi H, Xiao Z, Liu J, Locasale JW, Digman MA, Mjolsness E, Kong M, Werb Z, Lawson DA. Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing. Nat Cell Biol. 2020 03; 22(3):310-320.
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  3. Marsh T, Kenific CM, Suresh D, Gonzalez H, Shamir ER, Mei W, Tankka A, Leidal AM, Kalavacherla S, Woo K, Werb Z, Debnath J. Autophagic Degradation of NBR1 Restricts Metastatic Outgrowth during Mammary Tumor Progression. Dev Cell. 2020 Mar 09; 52(5):591-604.e6.
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  4. Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, Fearon D, Greten FR, Hingorani SR, Hunter T, Hynes RO, Jain RK, Janowitz T, Jorgensen C, Kimmelman AC, Kolonin MG, Maki RG, Powers RS, Puré E, Ramirez DC, Scherz-Shouval R, Sherman MH, Stewart S, Tlsty TD, Tuveson DA, Watt FM, Weaver V, Weeraratna AT, Werb Z. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020 03; 20(3):174-186.
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  5. Owyong M, Chou J, van den Bijgaart RJ, Kong N, Efe G, Maynard C, Talmi-Frank D, Solomonov I, Koopman C, Hadler-Olsen E, Headley M, Lin C, Wang CY, Sagi I, Werb Z, Plaks V. MMP9 modulates the metastatic cascade and immune landscape for breast cancer anti-metastatic therapy. Life Sci Alliance. 2019 12; 2(6).
    View on PubMed
  6. Hagerling C, Gonzalez H, Salari K, Wang CY, Lin C, Robles I, van Gogh M, Dejmek A, Jirström K, Werb Z. Immune effector monocyte-neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer. Proc Natl Acad Sci U S A. 2019 10 22; 116(43):21704-21714.
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  7. McGinnis CS, Patterson DM, Winkler J, Conrad DN, Hein MY, Srivastava V, Hu JL, Murrow LM, Weissman JS, Werb Z, Chow ED, Gartner ZJ. MULTI-seq: sample multiplexing for single-cell RNA sequencing using lipid-tagged indices. Nat Methods. 2019 07; 16(7):619-626.
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  8. Lawson DA, Kessenbrock K, Davis RT, Pervolarakis N, Werb Z. Tumour heterogeneity and metastasis at single-cell resolution. Nat Cell Biol. 2018 12; 20(12):1349-1360.
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  9. 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 10 08; 34(4):561-578.e6.
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  10. Gonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 2018 10 01; 32(19-20):1267-1284.
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  11. 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 05 23; 9(1):2028.
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  12. 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 02 01; 32(3-4):244-257.
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  13. 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 01 30; 115(5):E992-E1001.
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  14. 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.
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  15. Gonzalez H, Robles I, Werb Z. Innate and acquired immune surveillance in the postdissemination phase of metastasis. FEBS J. 2018 02; 285(4):654-664.
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  16. 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 02; 9(1):20-33.
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  17. Shahi P, Wang CY, Chou J, Hagerling C, Gonzalez Velozo H, Ruderisch A, Yu Y, Lai MD, Werb Z. GATA3 targets semaphorin 3B in mammary epithelial cells to suppress breast cancer progression and metastasis. Oncogene. 2017 10 05; 36(40):5567-5575.
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  18. 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.
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  19. 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.
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  20. 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

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