1. Xue Y., Meehan B., Fu Z., Wang X.Q.D., Fiset P., Rieker R., Levins C., Kong T., Zhu X., Morin G., Skerritt L., Esther H., Venneti S., Martinez D., Jung S., Gonzalez A.V., Guiot M.C., Lockwood W., Spicer J., Agaimy A., Pastor W.A., Dostie J., Rak J., Foulkes W.D., Huang S. (2019) SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in non-small cell lung cancer. Nature Communications. 10(1): 557.
A collaboration with the lab of Sidong Huang (McGill University). The Huang lab had discovered that ovarian and lung cancers with null mutations of the chromatin remodeller SMARCA4 show down regulation of Cyclin D1, making these cancers vulnerable to cyclin dependent kinase inhibitors. We performed bioinformatic analysis of ATAC and ChIP-seq data to demonstrate an indirect mechanism whereby SMARCA4 upregulates the transcription factor JUN, which in turn regulates Cyclin D1, potentially by opening adjacent enhancers. This paper isn't part of our lab's main research program, but it is a good illustration of the bioinformatic techniques we use.
2. Cinkornpumin J.K., Kwon S.Y., Guo Y., Hossain I., Sirois J., Russett C.S., Tseng H., Okae H., Arima T., Duchaine T.F., Liu W., Pastor W.A. (2020) Naive Human Embryonic Stem Cells Can Give Rise to Cells with a Trophoblast-like Transcriptome and Methylome. Stem Cell Reports 15:1.
The first developmental decision that arises in mammalian embryogenesis is specification of the trophoblast (future placenta). For practical and ethical reasons, this period of development is very difficult to study, so we sought to model trophoblast specification using stem cells. In this paper, we demonstrate the we can convert specially cultured "naive" human embryonic stem cells (hESCs) into cells very similar to human trophoblast stem cells (hTSCs). We show how to purify such "transdifferentiated" hTSCs and demonstrate that they can grow and differentiate similar to real hTSCs purified from placenta. They also acquire a pattern of DNA methylation similar to what normally arises in placental development. We thus have a system to model the specification and the epigenetic patterning of placenta.
(For a list of Dr. Pastor's papers as a graduate student and postdoctoral fellow, see Google Scholar Citations)