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
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
- Taylor SK, Houshdaran S, Robinson JF, Gormley MJ, Kwan EY, Kapidzic M, Schilling B, Giudice LC, Fisher SJ. Cytotrophoblast extracellular vesicles enhance decidual cell secretion of immune modulators via TNFa. Development. 2020 Sep 08; 147(17).
View on PubMed - Quanquin NM, Barres LG, Aliyari SR, Day NT, Gerami H, Fisher SJ, Kakuru A, Kamya MR, Havlir DV, Feeney M, Dorsey G, Cheng G, Gaw SL. Gravidity-dependent associations between interferon response and birth weight in placental malaria. Malar J. 2020 Aug 05; 19(1):280.
View on PubMed - Varshavsky JR, Sen S, Robinson JF, Smith SC, Frankenfield J, Wang Y, Yeh G, Park JS, Fisher SJ, Woodruff TJ. Racial/ethnic and geographic differences in polybrominated diphenyl ether (PBDE) levels across maternal, placental, and fetal tissues during mid-gestation. Sci Rep. 2020 07 22; 10(1):12247.
View on PubMed - McNally L, Zhou Y, Robinson JF, Zhao G, Chen LM, Chen H, Kim MY, Kapidzic M, Gormley M, Hannibal R, Fisher SJ. Up-regulated cytotrophoblast DOCK4 contributes to over-invasion in placenta accreta spectrum. Proc Natl Acad Sci U S A. 2020 07 07; 117(27):15852-15861.
View on PubMed - Varshavsky JR, Robinson JF, Zhou Y, Puckett KA, Kwan E, Buarpung S, Aburajab R, Gaw SL, Sen S, Smith SC, Frankenfield J, Park JS, Fisher SJ, Woodruff TJ. Association of polybrominated diphenyl ether (PBDE) levels with biomarkers of placental development and disease during mid-gestation. Environ Health. 2020 06 03; 19(1):61.
View on PubMed - Sobhani NC, Avvad-Portari E, Nascimento ACM, Machado HN, Lobato DSS, Pereira JP, Esquivel MS, Vasconcelos ZC, Zin AA, Tsui I, Adachi K, Brickley EB, Fisher SJ, Nielsen-Saines K, Brasil P, Moreira ME, Gaw SL. Discordant Zika Virus Findings in Twin Pregnancies Complicated by Antenatal Zika Virus Exposure: A Prospective Cohort. J Infect Dis. 2020 May 11; 221(11):1838-1845.
View on PubMed - Leon-Martinez D, Robinson JF, Zdravkovic T, Genbacev O, Gormley M, Mcmaster M, Fisher SJ, Bianco K. Trisomy 21 is Associated with Caspase-2 Upregulation in Cytotrophoblasts at the Maternal-Fetal Interface. Reprod Sci. 2020 01; 27(1):100-109.
View on PubMed - Mahadevan U, Fisher S, Riley L, Chambers C, Jain R, Robinson C. Reply. Gastroenterology. 2019 11; 157(5):1435-1436.
View on PubMed - Silverstein J, Kidder W, Fisher S, Hope TA, Maisel S, Ng D, Van Ziffle J, Atreya CE, Van Loon K. Hormone receptor expression of colorectal cancer diagnosed during the peri-partum period. Endocr Connect. 2019 Aug; 8(8):1149-1158.
View on PubMed - Reynoso-Prieto M, Takeda M, Prakobphol A, Seidman D, Averbach S, Fisher S, Smith-McCune K. Menstrual cycle-dependent alterations in glycosylation: a roadmap for defining biomarkers of favorable and unfavorable mucus. J Assist Reprod Genet. 2019 May; 36(5):847-855.
View on PubMed - Gaw SL, Hromatka BS, Ngeleza S, Buarpung S, Ozarslan N, Tshefu A, Fisher SJ. Differential Activation of Fetal Hofbauer Cells in Primigravidas Is Associated with Decreased Birth Weight in Symptomatic Placental Malaria. Malar Res Treat. 2019; 2019:1378174.
View on PubMed - Robinson JF, Kapidzic M, Hamilton EG, Chen H, Puckett KW, Zhou Y, Ona K, Parry E, Wang Y, Park JS, Costello JF, Fisher SJ. Genomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts. Toxicol Sci. 2019 01 01; 167(1):211-226.
View on PubMed - Obimbo MM, Zhou Y, McMaster MT, Cohen CR, Qureshi Z, Ong'ech J, Ogeng'o JA, Fisher SJ. Placental Structure in Preterm Birth Among HIV-Positive Versus HIV-Negative Women in Kenya. . 2019 01 01; 80(1):94-102.
View on PubMed - Godoy PM, Bhakta NR, Barczak AJ, Cakmak H, Fisher S, MacKenzie TC, Patel T, Price RW, Smith JF, Woodruff PG, Erle DJ. Large Differences in Small RNA Composition Between Human Biofluids. Cell Rep. 2018 10 30; 25(5):1346-1358.
View on PubMed - Garrido-Gomez T, Fisher SJ, Simón C. Reply to Liu et al.: Decidualization defect in severe preeclampsia. Proc Natl Acad Sci U S A. 2018 08 14; 115(33):E7656-E7657.
View on PubMed - Nguyen TPH, Yong HEJ, Chollangi T, Brennecke SP, Fisher SJ, Wallace EM, Ebeling PR, Murthi P. Altered downstream target gene expression of the placental Vitamin D receptor in human idiopathic fetal growth restriction. . 2018; 17(2):182-190.
View on PubMed - Erlebacher A, Fisher SJ. Baby's First Organ. Sci Am. 2017 Sep 19; 317(4):46-53.
View on PubMed - Garrido-Gomez T, Dominguez F, Quiñonero A, Diaz-Gimeno P, Kapidzic M, Gormley M, Ona K, Padilla-Iserte P, McMaster M, Genbacev O, Perales A, Fisher SJ, Simón C. Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology. Proc Natl Acad Sci U S A. 2017 10 03; 114(40):E8468-E8477.
View on PubMed - Clancy AJ, Anthony DB, Fisher SJ, Leese HS, Roberts CS, Shaffer MSP. Reductive dissolution of supergrowth carbon nanotubes for tougher nanocomposites by reactive coagulation spinning. Nanoscale. 2017 Jun 29; 9(25):8764-8773.
View on PubMed - Robinson JF, Kapidzic M, Gormley M, Ona K, Dent T, Seifikar H, Hamilton EG, Fisher SJ. Transcriptional Dynamics of Cultured Human Villous Cytotrophoblasts. Endocrinology. 2017 06 01; 158(6):1581-1594.
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