Increasing evidence suggests that epigenetic regulation of chromatin states strongly influences gene expression and cell fate choices, and its deregulation could therefore be a critical aspect to development and disease. My research focuses on understanding how chromatin-modifying enzymes control cell fate decisions during pancreas development, and elucidating the epigenetic and transcriptional mechanisms that underlie pancreatic lesion. We utilized both mouse genetic approaches and a parallel hESC-based in vitro differentiation system which recapitulates the sequence of events observed during in vivo pancreas development, where pluripotent cells first commit to endoderm, then primitive gut tube, posterior foregut, and subsequently pancreas. Using this differentiation platform, we have begun to dissect the epigenetic events that drive pancreatic development. Additional ongoing research in my laboratory includes:
Using high-throughput sequencing and genome-editing technologies to study the DNA and histone modifications in pancreatic cancer, elucidating the role of chromatin modification enzymes in mouse models, and exploring novel anti-cancer or preventive strategies by targeting key epigenetic pathways.
In vitro differentiation of patient-specific iPS/hES cells as models of pancreatic diseases, such as diabetes mellitus