Doctor of Philosophy, University of California Berkeley (2010)
Bachelor of Arts, University of Chicago, Biology (2004)
Julie Baker, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
I am interested in understanding the development and evolution of the placenta, a mammalian specific organ crucial for fetal well-being. A key feature of the placenta are polyploid trophoblast cells that invade and remodel the mother’s uterus in order to promote blood flow and nutrient delivery to the fetus. In rodents, these cells are called trophoblast giant cells (TGCs) and have up to 1,000N DNA content due to endoreplication. As recent work has shown that TGC endoreplication is essential for fetal health, my research uses mouse knock-outs and genomics to elucidate the function of endopolyploidy. In addition, I am studying human trophoblast cells, as defects in these cells have drastic consequences for both fetal and maternal health, including accreta, preeclampsia and preterm birth, yet very little is understood about the molecular mechanisms behind these diseases.
Selective Amplification of the Genome Surrounding Key Placental Genes in Trophoblast Giant Cells
2016; 26 (2): 230-236
While most cells maintain a diploid state, polyploid cells exist in many organisms and are particularly prevalent within the mammalian placenta , where they can generate more than 900 copies of the genome . Polyploidy is thought to be an efficient method of increasing the content of the genome by avoiding the costly and slow process of cytokinesis [1, 3, 4]. Polyploidy can also affect gene regulation by amplifying a subset of genomic regions required for specific cellular function [1, 3, 4]. This mechanism is found in the fruit fly Drosophila melanogaster, where polyploid ovarian follicle cells amplify genomic regions containing chorion genes, which facilitate secretion of eggshell proteins . Here, we report that genomic amplification also occurs in mammals at selective regions of the genome in parietal trophoblast giant cells (p-TGCs) of the mouse placenta. Using whole-genome sequencing (WGS) and digital droplet PCR (ddPCR) of mouse p-TGCs, we identified five amplified regions, each containing a gene family known to be involved in mammalian placentation: the prolactins (two clusters), serpins, cathepsins, and the natural killer (NK)/C-type lectin (CLEC) complex [6-12]. We report here the first description of amplification at selective genomic regions in mammals and present evidence that this is an important mode of genome regulation in placental TGCs.
View details for DOI 10.1016/j.cub.2015.11.060
View details for Web of Science ID 000368972300026
View details for PubMedID 26774788
Copy number variation is a fundamental aspect of the placental genome.
2014; 10 (5)
Discovery of lineage-specific somatic copy number variation (CNV) in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal, and even essential, aspect of cell biology. We show that 1,000 N polyploid trophoblast giant cells (TGCs) of the mouse placenta contain 47 regions, totaling 138 Megabases, where genomic copies are underrepresented (UR). UR domains originate from a subset of late-replicating heterochromatic regions containing gene deserts and genes involved in cell adhesion and neurogenesis. While lineage-specific CNVs have been identified in mammalian cells, classically in the immune system where V(D)J recombination occurs, we demonstrate that CNVs form during gestation in the placenta by an underreplication mechanism, not by recombination nor deletion. Our results reveal that large scale CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during embryogenesis and are propagated by a mechanism of underreplication.
View details for DOI 10.1371/journal.pgen.1004290
View details for PubMedID 24785991
Evolutionary perspectives into placental biology and disease
Applied & Translational Genomics
2013; 2: 64-69
View details for DOI 10.1016/j.atg.2013.07.001