Year 2

Our laboratory is known for its discovery of the family of nuclear hormone receptors (NHRs) that use hormones to control genes and thereby regulate embryonic development, cell growth, physiology and metabolism. Our goal is to explore how NHRs activate gene networks to produce human induced pluripotent stem cells (hiPSCs). We will determine the specific sites on the genome where NHRs and the reprogramming factor (Oct4) bind and determine how binding results in “epigenetic” modifications. One of our main goals is a massive project to compile all of the gene expression changes in adipose- and keratinocyte-derived hiPSCs, embryonic stem cells, and parental somatic cells. Gene expression differences between somatic, embryonic stem and hiPSC cell types may influence their differentiation capabilities. We are currently performing experiments to map the sites of histone modifications and will correlate these sites with the previously identified DNA methylation sites and the gene expression changes. We are currently on track to complete the stated milestones and goals of the funded project.