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Susan Fisher, PhD

Title: Professor
School: UCSF School of Medicine
Department: Ob/Gyn, Reproductive Sciences
Email: Susan.Fisher@ucsf.edu
profiles.ucsf.edu/susan.fisher

Overview

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.

Research Activities and Funding

THC effects on human implantation: role of trophoblast CB1
NIH/NIDA R21DA042951
Feb. 1, 2017 - Jan. 31, 2019 | Role: Principal Investigator

Dissecting gene dysregulation at the maternal-fetal interface in preeclampsia
NIH/NICHD R01HD076253
Sept. 25, 2013 - June 30, 2018 | Role: Principal Investigator

The UCSF Pregnancy Exposures to Environmental Chemicals (PEEC) Children's Center
NIH/NIEHS P01ES022841
June 15, 2013 - May 31, 2018 | Role: Co-Investigator

A Novel Model for Assessing the Effects of BPA Exposures on Human Placentation
NIH/NIEHS R21ES019944
Sept. 20, 2012 - Aug. 31, 2014 | Role: Principal Investigator

Fetal Programming and Environmental Exposures: Implications for Prenatal Care and
NIH/NIEHS R13ES021699
Aug. 7, 2012 - June 30, 2013 | Role: Co-Principal Investigator

Functional Glycomics of Human Saliva
NIH/NIDCR R01DE021041
April 1, 2011 - March 31, 2016 | Role: Principal Investigator

Molecular Mechanisms of Plasmodium Falciparum Adherence to the Human Placenta
NIH/NIAID R21AI079329
May 7, 2009 - April30, 2012 | Role: Principal Investigator

The Immune Paradox of Human Pregnancy: Fetal Trophoblasts and Maternal Leukocytes
NIH/NICHD R21HD055638
Aug. 1, 2008 - July 31, 2011 | Role: Principal Investigator

Origins and Biological Consequences of Human Infertility
NIH/NICHD P50HD055764
May 3, 2007 - March 31, 2017 | Role: Co-Investigator

Targeted and global proteomic strategies for early breast cancer detection
NIH/NCI U24CA126477
Sept. 28, 2006 - Aug. 31, 2013 | Role: Principal Investigator

Neuronal Guidance Mechanisms in Placental Development
NIH/NICHD R01HD046744
Dec. 15, 2004 - Nov. 30, 2010 | Role: Principal Investigator

Cataloguing the Human Salivary Proteome
NIH/NIDCR U01DE016274
Sept. 24, 2004 - May 31, 2010 | Role: Principal Investigator

Trophoblast Selectins and Their Uterine Mucin Ligands
NIH/NICHD U01HD042283
April 1, 2002 - March 31, 2008 | Role: Principal Investigator

GORDON RESEARCH CONFERENCE ON REPRODUCTIVE TRACT BIOLOGY
NIH/NICHD R13HD039168
May 1, 2000 - April 30, 2001 | Role: Principal Investigator

A NOVEL VASCULOGENESIS PROGRAM IN CYTOTROPHOBLASTS
NIH/NHLBI R01HL064597
March 7, 2000 - Feb. 28, 2005 | Role: Principal Investigator

Cancer Center Support Grant
NIH/NCI P30CA082103
Aug. 5, 1999 - May 31, 2018 | Role: Co-Investigator

NEW STRATEGIES FOR ENHANCING TISSUE INTEGRITY AND REPAIR
NIH/NIDCR P60DE013058
Aug. 1, 1999 - July 31, 2006 | Role: Co-Investigator

CANDIDA ADHERENCE
NIH/NIDCR R01DE011350
Sept. 30, 1994 - Sept. 29, 1997 | Role: Principal Investigator

Mechanisms of Preeclampsia: Impact of Obesity
NIH P01HD030367
April 1, 1993 - March 31, 2014 | Role: Co-Investigator

DEVELOPMENTAL BIOLOGY OF THE IMPLANTING MAMMALIAN EMBRYO
NIH/NICHD P01HD026732
Feb. 1, 1991 - Jan. 31, 2002 | Role: Co-Investigator

MECHANISMS OF TROPHOBLAST INVASION DURING PLACENTATION
NIH/NICHD R01HD022518
Feb. 1, 1988 - Jan. 31, 1991 | Role: Principal Investigator

PRENATAL DIAGNOSIS USING FETAL CELLS FROM MATERNAL BLOOD
NIH/NICHD [N01HD082903])http://grantome.com/search?q=N01HD082903)
Dec. 31, 1987 - March 31, 1992 | Role: Principal Investigator

MOLECULAR MECHANISMS—BACTERIAL ADHERENCE TO CEMENTUM
NIH/NIDCR R37DE007244
April 1, 1985 - Feb. 28, 2009 | Role: Principal Investigator

MOLECULAR MECHANISMS--BACTERIAL ADHERENCE TO CEMENTUM
NIH/NIDCR R01DE007244
April 1, 1985 - March 31, 2004 | Role: Principal Investigator

Bio-Organic Biomedical Mass Spectrometry Resource
NIH P41RR001614
March 1, 1982 - May 31, 2015 | Role: Co-Investigator