In our lab
We are interested in mechanisms of cell fate decisions in the early mouse embryo and their application to the maintenance and differentiation of embryo-derived stem cells.
We combine tools of genetic manipulation, live imaging, proteomics and single cell expression analysis to explore the fundamental aspects of lineage development. For example, we are investigating epigenetic and regulatory differences between pluripotency and the extraembryonic stem cell state, since this is the key switch that marks loss of totipotency. We are also applying our developmental knowledge to the differentiation of human iPS cells into cell types suitable for exploring new aspects of human biology and disease.
We recently developed a CRISPR/Cas9-based genome editing method that allows for highly efficient, precise insertion of large DNA fragments into the mouse embryo genome. Two-cell homologous recombination (2C-HR)-CRISPR, is based on introducing CRISPR reagents into embryos at the two-cell stage, taking advantage of the open chromatin structure and the likely increase in homologous-recombination efficiency during the long G2 phase. We are currently exploiting this method to generate a number of mouse lines carrying fluorescent reporters, inducible protein degradation systems, optogenetic constructs and other synthetic biology tools.