Susan J. Fisher, PhD

Susan J. Fisher, PhD

Professor, Dept. of Obstetrics, Gynecology and Reproductive Sciences

Phone: (415) 476-5297
Box 0665, UCSF
San Francisco, CA

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Cancer Center Membership

Program Member » Breast Oncology

Research Summary

Our group works in three areas. In the first, we are studying the mechanisms used by the trophoblast cells of the human placenta to invade the uterus during normal pregnancy. Human fetal development depends on the embryo's ability to rapidly gain access to the maternal circulation. The cytotrophoblasts that form the fetal portion of the human placenta have solved this problem by transiently exhibiting certain invasive, tumor-like properties. Our studies show that, in normal pregnancy, cytotrophoblast invasion, both in vivo and in vitro, is accompanied by a dramatic switch in the cells' expression of matrix-degrading metalloproteinases and adhesion molecules. Function-perturbation experiments suggest that cytotrophoblasts carefully regulate their invasive potential by simultaneously expressing a number of molecules that either promote or inhibit invasion. Additionally, we found that cytotrophoblasts that replace the endothelial lining of uterine blood vessels also have the amazing ability to mimic the adhesion phenotype of vascular cells. This phenomenon is likely to be a critical component of normal placentation. What controls this highly unusual differentiation process? Since cytotrophoblasts target large-bore arterioles for invasion, we reasoned that oxygen tension could play a role. Recently, we showed that oxygen controls whether cells proliferate or exit the cell cycle and differentiate; Eph/ephrin family members, transmembrane ligands and receptors, pattern invasion in terms of arterial bias. Finally, we use information about molecular aspects of cytotrophoblast function in normal pregnancy to search for defects that are associated with pregnancy complications such as preeclampsia (e.g., dangerously high blood pressure). For example, our work shows that this pregnancy complication is characterized by specific aberrations in trophoblast secretion of vasculogenic/angiogenic substances.

In parallel, our lab has begun studying the earliest stages of human development using human embryonic stem cells as a model system. Our work to date has focused on deriving additional lines using feeders formed from human placental cells. We recently made the surprising discovery that the cells exhibit apical-basal type polarization. Currently we are investigating how this highly specialized phenomenon is related to pluripotency. Our recently funded CIRM comprehensive grant is focused on constructing a fate map of the human embryo.

Finally, we are using mass spectrometry-based approaches for proteome analyses. Three projects are under way. The first is compilation of an initial draft of the salivary proteome of healthy individuals as a first step in using this body fluid for diagnosis of common diseases. The second is an analysis of the primary proteome and protein complexes of the soil organism Desulfovibrio vulgaris. The goal of the third and newest project is to formulate novel methods that enable robust mass spectrometry-based platforms for the discovery of biomarkers in body fluid for the early detection of tumors.


Hope College, Holland, Michigan, A.B., 1972, Biology, Chemistry
University of Michigan, Ann Arbor, Michigan, 1973, Anatomy
University of Kentucky, Lexington, Kentucky, Ph.D., 1977, Anatomy
University of Kentucky, Lexington, KY, Postdoc, 1977-1982, Mass Spectrometry

Professional Experience

  • 1982-1988
    Assistant Professor, Dept. of Stomatology, University of California, San Francisco (UCSF), CA
  • 1988-1994
    Associate Professor, Dept. of Stomatology, UCSF, CA
  • 1994-2008
    Professor, Dept. of Cell and Tissue Biology, UCSF, CA
  • 2003-present
    Faculty Director, UCSF Sandler-Moore Mass Spectrometry Core Facility, UCSF, CA
  • 2004-present
    Director, Human Embryonic Stem Cell Program, UCSF, CA
  • 2008-present
    Professor, Dept. of Obstetrics, Gynecology and Reproductive Sciences, UCSF, CA

Honors & Awards

  • 1972-73
    NIH Training Grant
  • 1978-81
    NIH National Research Service Award HD05687
  • 1987
    UCSF Academic Senate Distinguished Teaching Award
  • 1988
    Pew Foundation Faculty Development Award
  • 1994
    Achievement Award in Women's Health (Warner-Lambert Co., National Health Council, Journal of Women's Health)
  • 2000
    Sadler Award from NICHD
  • 2000
    NIH MERIT Award (DE07244)
  • 2002
    UCSF Graduate Association Outstanding Mentor Award
  • 2004
    UCSF School of Dentistry Faculty Research Award
  • 2006
    Dean's Distinguished Lecturer (U of Colorado)
  • 2013
    Frontiers in Reproduction Research Program Pioneer Award (NIH, MBL and Burroughs Welcome)
  • 2013
    NICHD MERIT Award (HD076253)
  • 2014
    NIH State of the Art Lecture, International Federation of Placenta Associations

Selected Publications

  1. Fisher SJ. Why is placentation abnormal in preeclampsia? Am J Obstet Gynecol. 2015 Oct; 213(4 Suppl):S115-22.
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  2. Zdravkovic T, Nazor KL, Larocque N, Gormley M, Donne M, Hunkapiller N, Gnanaratnam G, Bernstein HS, Wei G, Hebrok M, Zeng X, Genbacev O, Mattis A, McMaster MT, Krtolica A, Valbuena D, Simón C, Laurent LC, Loring JF, and Fisher SJ. Human Stem Cells from Single Blastomeres Reveal Pathways of Embryonic or Trophoblast Fate Specification (in Press). Development. 2015.
    View on PubMed
  3. Integrative analysis of 111 reference human epigenomes. Nature. 2015 Feb 19; 518(7539):317-30.
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  4. Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ, Amin V, Whitaker JW, Schultz MD, Ward LD, Sarkar A, Quon G, Sandstrom RS, Eaton ML, Wu YC, Pfenning AR, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris RA, Shoresh N, Epstein CB, Gjoneska E, Leung D, Xie W, Hawkins RD, Lister R, Hong C, Gascard P, Mungall AJ, Moore R, Chuah E, Tam A, Canfield TK, Hansen RS, Kaul R, Sabo PJ, Bansal MS, Carles A, Dixon JR, Farh KH, Feizi S, Karlic R, Kim AR, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer TR, Neph SJ, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari RC, Siebenthall KT, Sinnott-Armstrong NA, Stevens M, Thurman RE, Wu J, Zhang B, Zhou X, Beaudet AE, Boyer LA, De Jager PL, Farnham PJ, Fisher SJ, Haussler D, Jones SJ, Li W, Marra MA, McManus MT, Sunyaev S, Thomson JA, Tlsty TD, Tsai LH, Wang W, Waterland RA, Zhang MQ, Chadwick LH, Bernstein BE, Costello JF, Ecker JR, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA, Wang T, Kellis M. . Roadmay Epigenomics Consortium: Integrative Analysis of 111 Reference Human Epigenomes. Nature. 2015; 518(19):317-330.
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  5. Fisher SJ, Giudice LC. Retrospective. Robert G. Edwards (1925-2013). Science. 2013 May 17; 340(6134):825.
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  6. Drake PM, Schilling B, Niles RK, Prakobphol A, Li B, Jung K, Cho W, Braten M, Inerowicz HD, Williams K, Albertolle M, Held JM, Iacovides D, Sorensen DJ, Griffith OL, Johansen E, Zawadzka AM, Cusack MP, Allen S, Gormley M, Hall SC, Witkowska HE, Gray JW, Regnier F, Gibson BW, Fisher SJ. Lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers. J Proteome Res. 2012 Apr 6; 11(4):2508-20.
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  7. Aghajanova L, Shen S, Rojas AM, Fisher SJ, Irwin JC, Giudice LC. Comparative transcriptome analysis of human trophectoderm and embryonic stem cell-derived trophoblasts reveal key participants in early implantation. Biol Reprod. 2012 Jan; 86(1):1-21.
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  8. Marchand M, Horcajadas JA, Esteban FJ, McElroy SL, Fisher SJ, Giudice LC. Transcriptomic signature of trophoblast differentiation in a human embryonic stem cell model. Biol Reprod. 2011 Jun; 84(6):1258-71.
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  9. Winn VD, Gormley M, Fisher SJ. The Impact of Preeclampsia on Gene Expression at the Maternal-Fetal Interface. Pregnancy Hypertens. 2011 Jan 1; 1(1):100-8.
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  10. Roberts RM, Fisher SJ. Trophoblast stem cells. Biol Reprod. 2011 Mar; 84(3):412-21.
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  11. Chung Y, Klimanskaya I, Becker S, Li T, Maserati M, Lu SJ, Zdravkovic T, Ilic D, Genbacev O, Fisher S, Krtolica A, Lanza R. Human embryonic stem cell lines generated without embryo destruction. Cell Stem Cell. 2008 Feb 7; 2(2):113-7.
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  12. Genbacev-Krtolica O. Highlight for phenols, quinolines, indoles, benzene and 2-cyclopenten-1-ones are oviduct toxicants in cigarette smoke, by Prue Talbot, Karen Riveles, and Ryan Rosa: list of tobacco-smoke constituents that are harmful for reproduction grows--passive smokers may be at risk. Toxicol Sci. 2005 Jul; 86(1):4-5.
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  13. Simón C, Escobedo C, Valbuena D, Genbacev O, Galan A, Krtolica A, Asensi A, Sánchez E, Esplugues J, Fisher S, Pellicer A. First derivation in Spain of human embryonic stem cell lines: use of long-term cryopreserved embryos and animal-free conditions. Fertil Steril. 2005 Jan; 83(1):246-9.
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  14. Fisher SJ. The placental problem: linking abnormal cytotrophoblast differentiation to the maternal symptoms of preeclampsia. Reprod Biol Endocrinol. 2004 Jul 5; 2:53.
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  15. Maidji E, Percivalle E, Gerna G, Fisher S, Pereira L. Transmission of human cytomegalovirus from infected uterine microvascular endothelial cells to differentiating/invasive placental cytotrophoblasts. Virology. 2002 Dec 5; 304(1):53-69.
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  16. Fisher SJ, Zhou Y, Huang L, Winn VD. When is seeing believing? The use of color Doppler ultrasound to diagnose placenta accreta in the first trimester of pregnancy. Ultrasound Obstet Gynecol. 2002 Jun; 19(6):540-2.
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  17. Paul P, Rouas-Freiss N, Moreau P, Cabestre FA, Menier C, Khalil-Daher I, Pangault C, Onno M, Fauchet R, Martinez-Laso J, Morales P, Villena AA, Giacomini P, Natali PG, Frumento G, Ferrara GB, McMaster M, Fisher S, Schust D, Ferrone S, Dausset J, Geraghty D, Carosella ED. HLA-G, -E, -F preworkshop: tools and protocols for analysis of non-classical class I genes transcription and protein expression. Hum Immunol. 2000 Nov; 61(11):1177-95.
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  18. Fisher S, Genbacev O, Maidji E, Pereira L. Human cytomegalovirus infection of placental cytotrophoblasts in vitro and in utero: implications for transmission and pathogenesis. J Virol. 2000 Aug; 74(15):6808-20.
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  19. Goldman-Wohl DS, Ariel I, Greenfield C, Hochner-Celnikier D, Cross J, Fisher S, Yagel S. Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia. Mol Hum Reprod. 2000 Jan; 6(1):88-95.
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  20. Rohde LH, Janatpore MJ, McMaster MT, Fisher S, Zhou Y, Lim KH, French M, Hoke D, Julian J, Carson DD. Complementary expression of HIP, a cell-surface heparan sulfate binding protein, and perlecan at the human fetal-maternal interface. Biol Reprod. 1998 Apr; 58(4):1075-83.
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