Welcome to the Baker Lab!
The Baker lab examines genetic and developmental aspects of placental biology, ranging from differentiation to disease. We use multiple model systems, including murine embryos, stem cells, and human tissues, to ask and answer questions about how cell types are formed, how they communicate in a rapidly changing environment, how they’ve evolved, and how all of this might contribute to disease.
Scroll down for highlights of what’s happening in the lab!
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.