Susan J. Fisher, PhD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Susan J. Fisher, PhD

Professor, Dept. of Obstetrics, Gynecology and Reproductive Sciences

sfisher@cgl.ucsf.edu

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

UCSF Profiles | Fisher Lab

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.

Education

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. Bianco K, Gormley M, Farrell J, Zhou Y, Oliverio O, Tilden H, McMaster M, Fisher SJ. Placental transcriptomes in the common aneuploidies reveal critical regions on the trisomic chromosomes and genome-wide effects. Prenat Diagn. 2016 Sep; 36(9):812-22.
    View on PubMed
  2. Lorenzon-Ojea AR, Guzzo CR, Kapidzic M, Fisher SJ, Bevilacqua E. Stromal Cell-Derived Factor 2: A Novel Protein that Interferes in Endoplasmic Reticulum Stress Pathway in Human Placental Cells. Biol Reprod. 2016 Aug; 95(2):41.
    View on PubMed
  3. Genbacev O, Larocque N, Ona K, Prakobphol A, Garrido-Gomez T, Kapidzic M, Bárcena A, Gormley M, Fisher SJ. Integrin a4-positive human trophoblast progenitors: functional characterization and transcriptional regulation. Hum Reprod. 2016 Jun; 31(6):1300-14.
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  4. Ponder KL, Bárcena A, Bos FL, Gormley M, Zhou Y, Ona K, Kapidzic M, Zovein AC, Fisher SJ. Preeclampsia and Inflammatory Preterm Labor Alter the Human Placental Hematopoietic Niche. Reprod Sci. 2016 Mar 3.
    View on PubMed
  5. 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 8; 113(10):E1343-51.
    View on PubMed
  6. Shatsky M, Allen S, Gold BL, Liu NL, Juba TR, Reveco SA, Elias DA, Prathapam R, He J, Yang W, Szakal ED, Liu H, Singer ME, Geller JT, Lam BR, Saini A, Trotter VV, Hall SC, Fisher SJ, Brenner SE, Chhabra SR, Hazen TC, Wall JD, Witkowska HE, Biggin MD, Chandonia JM, Butland G. Bacterial Interactomes: Interacting Protein Partners Share Similar Function and Are Validated in Independent Assays More Frequently Than Previously Reported. Mol Cell Proteomics. 2016 May; 15(5):1539-55.
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  7. Robinson JF, Gormley MJ, Fisher SJ. A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity. Reprod Toxicol. 2016 Apr; 60:1-10.
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  8. Albertolle ME, Hassis ME, Ng CJ, Cuison S, Williams K, Prakobphol A, Dykstra AB, Hall SC, Niles RK, Ewa Witkowska H, Fisher SJ. Mass spectrometry-based analyses showing the effects of secretor and blood group status on salivary N-glycosylation. Clin Proteomics. 2015; 12:29.
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  9. Zdravkovic T, Nazor KL, Larocque N, Gormley M, Donne M, Hunkapillar N, Giritharan 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, Fisher SJ. Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification. Development. 2015 Dec 1; 142(23):4010-25.
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  10. Maltepe E, Fisher SJ. Placenta: The Forgotten Organ. Annu Rev Cell Dev Biol. 2015 Nov 13; 31:523-52.
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  11. Fisher SJ. Why is placentation abnormal in preeclampsia? Am J Obstet Gynecol. 2015 Oct; 213(4 Suppl):S115-22.
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  12. 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.
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  13. Hassis ME, Niles RK, Braten MN, Albertolle ME, Ewa Witkowska H, Hubel CA, Fisher SJ, Williams KE. Evaluating the effects of preanalytical variables on the stability of the human plasma proteome. Anal Biochem. 2015 Jun 1; 478:14-22.
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  14. Integrative analysis of 111 reference human epigenomes. Nature. 2015 Feb 19; 518(7539):317-30.
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  15. Abbatiello SE, Schilling B, Mani DR, Zimmerman LJ, Hall SC, MacLean B, Albertolle M, Allen S, Burgess M, Cusack MP, Gosh M, Hedrick V, Held JM, Inerowicz HD, Jackson A, Keshishian H, Kinsinger CR, Lyssand J, Makowski L, Mesri M, Rodriguez H, Rudnick P, Sadowski P, Sedransk N, Shaddox K, Skates SJ, Kuhn E, Smith D, Whiteaker JR, Whitwell C, Zhang S, Borchers CH, Fisher SJ, Gibson BW, Liebler DC, MacCoss MJ, Neubert TA, Paulovich AG, Regnier FE, Tempst P, Carr SA. Large-Scale Interlaboratory Study to Develop, Analytically Validate and Apply Highly Multiplexed, Quantitative Peptide Assays to Measure Cancer-Relevant Proteins in Plasma. Mol Cell Proteomics. 2015 Sep; 14(9):2357-74.
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  16. 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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  17. Fisher SJ, Blakeley MP, Howard EI, Petit-Haertlein I, Haertlein M, Mitschler A, Cousido-Siah A, Salvay AG, Popov A, Muller-Dieckmann C, Petrova T, Podjarny A. Perdeuteration: improved visualization of solvent structure in neutron macromolecular crystallography. Acta Crystallogr D Biol Crystallogr. 2014 Dec 1; 70(Pt 12):3266-72.
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  18. Williams KE, Miroshnychenko O, Johansen EB, Niles RK, Sundaram R, Kannan K, Albertolle M, Zhou Y, Prasad N, Drake PM, Giudice LC, Hall SC, Witkowska HE, Buck Louis GM, Fisher SJ. Urine, peritoneal fluid and omental fat proteomes of reproductive age women: Endometriosis-related changes and associations with endocrine disrupting chemicals. J Proteomics. 2015 Jan 15; 113:194-205.
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  19. Robinson JF, Fisher SJ. Rbpj links uterine transformation and embryo orientation. Cell Res. 2014 Sep; 24(9):1031-2.
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  20. Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science. 2014 Aug 15; 345(6198):760-5.
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