The biological systems we routinely use include differentiation of pluripotent stem cells (PSCs) including human PSC and mouse ES cells (mES). The approaches we use including gene editing, epigenomic profiling, RNA (mRNA and noncoding RNA) profiling, bioinformatic analysis, biochemistry, and cell biology approaches. Our research focuses on the following three areas.

1. Basic research aimed to provide insights for fundamental epigenetic questions such as mechanisms regulating locus-specific epigenetic modifications. Although we are using pluripotent stem cells and tractable metabolic cell types including hepatocytes and pancreatic beta cells to study maturation and its epigenetic basis, our quest for the basic mechanisms regulating pluripotency and tissue maturation could be applicable to other cell types.

2. Applications in disease research. Our research is relevant to common human disease, and the insight from epigenetic change could be adopted to discovery of new medicines to address pressing problems including metabolic diseases and cancer. Many human diseases are associated with epigenetic silencing of critical genes, or expression of ectopic genes that escapes epigenetic silencing. Patients’ iPS based disease modeling could contribute to identification of treatment approaches.

3. Technology platform development in several areas: new differentiation to generate functionally mature cell types from PSCs as a renewable source; molecular biological reagents to regulate gene expression and epigenetic landscape in disease-relevant cell types; advanced sequencing approaches, analytical methods to probe gene expression, and epigenetic properties during development, normal physiology, and in disease.