Research in our lab is concerned with understanding the molecular regulation of early developmental processes in vertebrate embryos. We primarily use the chicken embryo/as a model organism, and approach research questions from the dual perspective of how individual molecules function and how their functions can be integrated into regulatory networks. Present projects are focused on mechanisms regulating epithelial-mesenchymal transition (EMT) during gastrulation, endothelial cell development, cardiac myogenesis, and developing genomic and computational tools. We also host the GEISHA high throughput in situ hybridization gene expression project.
EMT and Gastrulation:
One group of projects are concerned with understanding epithelial mesenchymal transition (EMT) during avian gastrulation. Using “whole genome” microarrays printed in our laboratory, we are developing gene expression profiles of the cell layers and structures of the early embryo. Analysis of cell layers in and near the streak show that more than 1800 genes are upgregulated, and at least 700 genes are downregualted, in the preingression epiblast immediately adjacent to the primitive streak. Many of these genes are regulated by Fgf signaling, including members of several other signaling pathways and at least three dozen transription factors. Fgf signaling therefore appears to be a key upstream regulator of EMT. Studies are investigating signaling pathways downstream of Fgf receptor activation. The MAPK pathway in particular directly regulates downstream gene transcription via activation of several transcription factors, including members of the Ets and T Box families. Studies are investigating transcriptional targets of these factors tjhat regulate cell ingression and EMT.
Another long standing research interest is the mechanisms controlling early stages of cardiac myogenesis and endothelial cell development, Bmp and Fgf signaling are well known activators of genes in the cardiogenic pathway, however relatively few direct transcriptional targets of these signaling pathways have been identified. By combining classical experimental embryological approaches, and signaling pathway perturbation with with microarray analyses, we are working to generate a comprehensive network model of the regualtory pathways controlling cardiac myogenesis. Studies are also investigating the molecular origin of endothelial cells. Despite a huge literature concerning endothelial cell biology, the regulatory pathways leading from emerging mesoderm to differentiated endothelial cells remains largelyunknown.
Recently, the lab has also begun developing tools and approaches for understanding the developmental processes described above from more a holistic perspective of gene regulatory networks. We are approaching this from a biological and machine learning perspectives.