Baker lab members
The lab
Julie Baker, PhD
Associate Professor
Se-Jin Yoon, PhD
Postdoc
I am investigating the Nodal signaling pathway including the transcriptional factor complex containing Smad2/3 and FoxH1 required for the establishment of endoderm as well as the maintenance of pluripotency in hESCs. An understanding of the Nodal pathway and its downstream targets is critical for unraveling the interlocking mechanisms underlying both pluripotency and early cell fate commitment. To identify Nodal signaling targets in hESCs and endodermal cells, I have accomplished the genome-wide screening of Smad/FoxH1 downstream targets in undifferentiated hESCs and endoderm differentiated hESCs via ChIP with ultra high throughput sequencing. The analysis of the Smad/FoxH1 transcription factor binding network in this two different cell types will provide a glimpse at the genomic mechanism behind the early stages of differentiation in human.
Postdoc
My goal is to answer the questions as to whether and how the molecular regulation of cell cycle is mechanistically coupled to cell fate decisions in hESCs and find a way to decrease the risk of tumorigenic potential if hESCs are to be used therapeutically. Currently I am characterizing the cell cycle dependent genome-wide transcriptome in undifferentiated hESCs compared with early differentiated hESCs and investigating the biological function of certain cell cycle regulators which probably function in balancing self-renewal versus differentiation in hESCs. My other role in Baker lab is to derive new hESC lines containing disease-associated mutations for the future disease research and therapies.
Postdoc
I am interested in understanding the development and evolution of the placenta, a mammalian specific organ crucial for fetal wellbeing. 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 1,000c 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 preeclampsia and preterm birth, yet very little is understood about the molecular mechanisms behind these diseases.
Postdoc
I am interested in the changes in transcriptional regulation that underlie early endoderm organogenesis. In vertebrates, the anterior endoderm gives rise to several organs, including the liver, thyroid, lung, and pancreas. What are the key changes in transcriptional profile and cell behavior that initially distinguish the progenitors of each of these organs from each other, and how deeply are these mechanisms conserved? My research currently uses the frog Xenopus tropicalis to begin to address these questions by characterizing the expression and function of transcriptional targets of the Nodal signaling pathway, an essential regulator of endoderm specification. In the future, I hope to complement work in Xenopus with studies in mice and human embryonic stem cells to better articulate the mechanisms of early endoderm organogenesis.
Rakhi Gupta
Research Assistant
Xenopus Tropicalis embryo is one of the best tools to explore gene regulatory network. Presently, my research focus is to understand signaling pathways involved in endoderm commitment. As a part of this investigation, I will be performing Chromatin Immunoprecipitation, using different transcription factors such as Smad2/3, smad4, β-catenin, Gata6, Sox17β, FoxH1 and FoxA2 at multiple time points during blastula and gastrula stages, followed by massively parallel sequencing (ChIPSeq). In addition, I will be using 3Seq technique on isolated endoderm maintaining same time point as ChIPSeq to analyze transcriptome and compare ChipSeq data with 3Seq data to have a better understanding of endoderm gene regulatory network.
PhD student, Genetics
I am investigating the evolution of the mammalian placenta, which is a recent adaptation that allowed eutherians and marsupials to give live birth. The availability of three mammalian taxa (eutherian, marsupial, monotremes) each with varying levels of placenta complexity opens a unique opportunity to examine the evolution of a novel organ. I am utilizing functional and comparative genomics to compare the placenta developmental genetic networks of eutherians and marsupials, in hopes of retracing the genomic events (novel gene evolution, duplication, co-option, etc) that gave rise to this novel organ. As a part of the project we have developed a collaboration with Marilyn Renfree of the University of Melbourne in Australia and the Kangaroo Genomics group.
PhD student, Genetics
I am interested in the epigenetic regulation of placental development, in particular the role of DNA methylation. The epigenetic profile of the placenta appears to be more flexible and dynamic than the embryo proper, as evidenced by significantly lower levels of total DNA methylation and striking loss of imprinting at many loci in extraembryonic tissues. However, knockouts or inhibition of the DNA-methylating enzymes (DNMTs) result in malformation of the placenta. I am examining the role of DNMTs in the placenta with tissue-specific knockdowns, and using high throughput sequencing techniques to clarify the extent of loss of imprinting in the placenta.
PhD student, Developmental Biology
I am interested in how major developmental pathways such as the Nodal signaling pathway diversify their downstream effects on gene activation and morphogenesis using a limited amount of effectors depending on different developmental contexts. In Xenopus, the Nodal signaling pathway is involved in specification of mesendoderm, gastrulation and left-right asymmetry. Several Nodal ligands act through type I and type II receptors, resulting in phosphorylation and activation of receptor-activated SMADs. Once activated, the SMADs enter the nucleus and associate with other binding partners such as FOXH1, E2A and HEB, which modify the affinity of the SMAD complex for different sites in the genome. Currently, I am using ChIP-Seq to assess changes in the occupancy of SMAD binding sites in the genome after individual knockdown of Nodal ligands and SMAD binding partners like E2A. Research suggests that changes in the kinetics of SMAD shuttling between cellular compartments results in differential gene expression. Along with Andrea Wills, I am planning to use GFP fusion and bimolecular fluorescence complementation experiments to study the effects or different Nodal ligands on the shuttling of SMADs and their binding partners between the cytoplasm and the nucleus.
Alumni
Siwan Kim - Postdoc
Yuqiong Pan - Postdoc
Chuba Oyolu - Bioengineering Ph.D.
Yvonne Chan - Undergrad (now: Medical student, UCLA)
Alayne Brunner - PhD (now: Postdoc, Rob West lab Stanford)
Kirstin Knox - Genetics MD/Ph.D.
Nesanet Mitiku - MD/Ph.D.
Eric Chiao - Post-Doc
Andy Hufton - Ph.D
Muriel Kmet - RA
Annette Borchers - Post-Doc
Amy Kim - Masters
Jeff Leonard - RA
Kari Dickinson - Ph.D.
Andrea Pomrhen - MD/Ph.D.
