Susan J. Fisher, PhD
Professor, Dept. of Obstetrics, Gynecology and Reproductive Sciences
Cancer Center Program Memberships
Affiliate MemberResearch 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
- Hall SC, Hassis ME, Williams KE, Albertolle ME, Prakobphol A, Dykstra AB, Laurance M, Ona K, Niles RK, Prasad N, Gormley M, Shiboski C, Criswell LA, Witkowska HE, Fisher SJ. Alterations in the Salivary Proteome and N-Glycome of Sjögren's Syndrome Patients. J Proteome Res. 2017 Apr 07; 16(4):1693-1705.
View on PubMed - Robinson JF, Kapidzic M, Gormley M, Ona K, Dent T, Seifikar H, Hamilton EG, Fisher SJ. Research Resource: Transcriptional Dynamics of Cultured Human Villous Cytotrophoblasts. Endocrinology. 2017 Mar 08.
View on PubMed - Slabodnick MM, Ruby JG, Reiff SB, Swart EC, Gosai S, Prabakaran S, Witkowska E, Larue GE, Fisher S, Freeman RM, Gunawardena J, Chu W, Stover NA, Gregory BD, Nowacki M, Derisi J, Roy SW, Marshall WF, Sood P. The Macronuclear Genome of Stentor coeruleus Reveals Tiny Introns in a Giant Cell. Curr Biol. 2017 Feb 08.
View on PubMed - 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 - 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 - 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.
View on PubMed - Bensing BA, Khedri Z, Deng L, Yu H, Prakobphol A, Fisher SJ, Chen X, Iverson TM, Varki A, Sullam PM. Novel aspects of sialoglycan recognition by the Siglec-like domains of streptococcal SRR glycoproteins. Glycobiology. 2016 Apr 1.
View on PubMed - 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 - 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 - 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.
View on PubMed - Robinson JF, Gormley MJ, Fisher SJ. A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity. Reprod Toxicol. 2016 Apr; 60:1-10.
View on PubMed - 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.
View on PubMed - Maltepe E, Fisher SJ. Placenta: The Forgotten Organ. Annu Rev Cell Dev Biol. 2015 Nov 13; 31:523-52.
View on PubMed - Fisher SJ. Why is placentation abnormal in preeclampsia? Am J Obstet Gynecol. 2015 Oct; 213(4 Suppl):S115-22.
View on PubMed - 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 - 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.
View on PubMed - Integrative analysis of 111 reference human epigenomes. Nature. 2015 Feb 19; 518(7539):317-30.
View on PubMed - 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.
View on PubMed - 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.
View on PubMed - 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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