Welcome to the Baker Lab!
The Baker laboratory examines the genomics underlying the differentiation and evolution of fetal cell types. We use multiple model systems, including frog and mouse embryos, embryonic stem cells, trophoblast stem cells and human tissues, to ask how cell types in the fetus form, how these cell types are regenerated, how particular lineages evolved and how these processes might lead to human disease.
Much of our work has focused on the establishment of the early germ layers, the ectoderm, mesoderm, endoderm and – in mammals – the trophectoderm.
Scroll down for highlights of some recent findings!
How do cells become endoderm and mesoderm?
We have discovered that the formation of mesoderm and endoderm depends on the interaction between the role of the HLH proteins, E2A and HEB, and the Nodal signaling pathway. Importantly, we have found that HEB also associates with the histone repressive mark, H3K27me3, to regulate developmental genes (Yoon et al., 2015). We also have shown that E2a is required for endoderm and mesoderm formation in the frog embryo and its role is both to activate developmental transcription factors and to repress the molecule Lefty (Wills et al., 2015).
Transposons guide evolution of trophectoderm.
In examining the genomics of trophoblast stem cells and placenta, we have been elucidating how this critical mammalian organ evolved. We find that a single transposable element has contributed 30% of the binding sites for the key transcription factors Cdx2, Eomes and Elf5 – all three being essential for establishment of the trophectodermal lineage in mammals (Chuong et al., 2013). We are continuing to examining the role of transposable elements in placentation.
The placental genome has regions of under and over amplification.
Placental cells are typically polyploid or multinucleated in all species and tolerate a significant amount of moisacism. In examining mouse polyploid placental cells, we find specific regions of under and over represented regions. Under amplified regions are highly enriched for sensory and adhesion genes whereas over represented regions are mainly placental hormones. Overall, we suggest that genomic copy number variation may be responsible for regulating specific classes of genes in the placenta (Hannibal et al., 2014).
The egg is the only cell that internalizes a foreign nucleus and efficiently and rapidly reprograms it to pluripotency. We have taken a genome wide approach to define how the egg reprograms cells. Transcriptomics and proteomics have revealed that the egg is a highly organized cell and this organization drives efficient reprogramming. Current work is focused on drawing parallels between somatic reprogramming and fertilization.
Tail regeneration in the tadpole
While pathways guiding cell fate specification in the embryo have been explored over the past 20 years, very little is known about how tissue regeneration occurs – particularly in the spinal cord. We have been examining the chromatin and transcriptome context of the regenerating spinal cord during a timeseries spanning hours post injury.
Diseases of pregnancy
We are investigating the genetics of preeclampsia in the Peruvian Altiplano and the disease accreta using genomic technologies.
Julie BakerPrincipal Investigator
Hi, my name is Julie!
Guillaume CornelisPostdoctoral Scholar
I am interested in the molecular and cellular mechanisms that can influence pace of life of organisms, as well as their evolutive history. More particularly, I am studying the impact of transposable elements (TEs) on the development of the mammalian placenta. TEs are mobile genetic elements scattered across vertebrate genomes. They have been shown to play critical roles in placentation, including as protein coding genes necessary for placental morphogenesis and as important enhancer elements that rewire the placental transcriptional circuitry. This active TE environment is entirely novel to the placental landscape as adult somatic tissues tightly repress TEs using specific epigenetic marks to specifically shut down these highly mutagenetic agents. The consequence, however, is extreme – inducing rapid evolution and potentially allowing for significant diseases associated with this organ, including cancer. My goal is to characterize the role of TEs cooptation in normal and pathological placenta, leading toward a better understanding of the development and evolution of placentation.
Outside of work, I like photography, movies and experimenting new cake recipes on my fellow labmates!
Roberta HannibalPostdoctoral Scholar
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 preeclampsia and preterm birth, yet very little is understood about the molecular mechanisms behind these diseases.
Christine ReidPostdoctoral Scholar
I’m originally from Southern California, and I went to University of Pennsylvania in Philadelphia for my PhD. I came to Stanford as a postdoc in the Baker Lab in late 2012, where I began work on reprogramming somatic cells using the Xenopus laevis oocyte. The oocyte reprograms cells efficiently and rapidly, but little is know about the factors that reprogram foreign nuclei. To define how the oocyte reprograms nuclei, I have characterized both proteins and transcripts within the oocyte. Current work is focused on profiling the chromatin state of the oocyte and the nuclei being reprogrammed. When I’m not in lab, I like hiking in the redwoods, hanging out at the beach and bike riding with my family.
Andrea WillsPostdoctoral Scholar
I spend a lot of my time puzzling over some big questions. Why do humans have such limited regeneration capacities, when other vertebrates like amphibians are readily able to regenerate structures like the heart, spinal cord, or limbs? Is regeneration of these tissues in amphibians basically a recapitulation of embryonic patterning events? What are the events in early embryogenesis that ultimately govern whether a cell will differentiate into one tissue like liver, while neighboring cells instead become another tissue like heart? I tackle these questions using a combination of genomics and embryology in the frog Xenopus tropicalis. I have been using genomics and transcriptomics approaches to identify how transcription factors interface with chromatin modifications during early embryogenesis to drive cell differentiation. More recently, I have applied these approaches to understand how chromatin and gene expression are remodeled during regeneration, and how these processes compare to early embryogenesis.
Outside of these puzzles, I spend my time running, reading old science fiction, and honing my toddler-wrangling skills.
Keyla Badillo-RiveraGraduate Student
I am interested in how different aspects of gene regulation alter placental tissue differentiation and function, and how that affects fetal development and puts the mother in risk. For this, I’m studying both mouse models and human cohorts. Right now, I am particularly looking at factors that affect the invasiveness of the placenta, such as endoreplication in trophoblast giant cells in mice, and previous uterine damage in humans.
Outside of lab, I mainly enjoy staying active. I’ve been dancing salsa for 6 years, and I am currently the director of Los Salseros de Stanford. I recently found a new hobby in rock climbing, and I love just being outdoors and enjoying the sun.
Jessica ChangGraduate Student
Since my time in the Baker Lab, I have been deeply engrossed in the remarkable capacity for Xenopus tropicalis tadpoles to regenerate. I am broadly interested in understanding how collections of genes interact over such a developmental time series. As such, I have been involved in utilizing large scale sequencing approaches to systematically identify and characterize patterns of activity that may characterize key biological processes involved in regeneration.
Outside of lab, I’m a huge fan of photography, tennis, and
really incredible reality television!
Eduardo Gonzalez-MaldonadoGraduate Student
Hi, I’m Eduardo!
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.
Michael GuernseyGraduate Student
I am interested in the genetic and developmental basis of adaptation in vertebrates. The placenta makes a fascinating case study in this context as this single organ displays a stunning amount of diversity in both form and function among mammals. Since joining the Baker lab I have been working on understanding the gene expression dynamics that underlie the maintenance of the Tamar wallaby placenta, a unique short-lived marsupial placenta.
What most people don’t realize is that the placenta is not an adaptation unique to mammals, but is also present in many fish and reptile species. Among these species the fish genus Poeciliopsis is particularly exciting because the placenta has evolved multiple times independently in this lineage. This allows us to ask whether the genes required for placenta establishment are the same or similar, implying molecular convergence, or whether evolution can use many different molecular mechanisms to achieve a similar adaptation. This is not possible in mammals where the placenta has evolved a single time. As we learn more I hope to understand whether the molecular phenomenon that shape mammalian placenta biology are also present in fish placentas (i.e. transposable elements, genomic imprinting, and variable ploidy).
Chris KaelinBarsh Lab Member
Hi, I’m Chris!
Hermie ManuelBarsh Lab Member
Hi, I’m Hermie!
Kelly McGowanBarsh Lab Member
Hi, I’m Kelly!