Epigenetic regulation in development and disease

During embryonic development patterns of gene expression are established that determine each cell type in the body. It is critically important that once genes are switched off, this repressive state is maintained throughout life, as dysregulation of this process can have severe developmental effects and lead to diseases such as cancer. Gene silencing is linked to the three-dimensional packaging of genomic DNA into chromatin which can be regulated through epigenetic mechanisms. In the lab we use cutting edge cell biology and bioinformatics approaches to study epigenetic regulation during development and how these processes are disrupted in cancer and neurodevelopmental disorders. Using human induced pluripotent stem cells (iPSCs) coupled with CRISPR-Cas9 genome modification strategies and cutting-edge epigenetic profiling techniques we can gain a deeper understanding of the mechanisms that govern gene expression during early development. We are also using pioneering structural biology approaches (cryo-electron tomography; Cryo-ET) to image chromatin at high resolution in cells. Crucially, this provides insight into how chromatin and epigenetic processes are dysregulated in disease and ultimately can be leveraged to develop new therapeutic strategies.