Levasseur, Dana, Ph.D

Embryonic stem (ES) cells are endowed with two distinguishing properties, they can regenerate themselves indefinitely (self-renewal) and simultaneously give rise to all tissues in the body (pluripotency). Broadly, the long-term objective of my laboratory is to identify and characterize transcription factors and nuclear proteins that regulate self-renewal and pluripotency. In one project, we are investigating the transcriptional and epigenetic regulation of the nuclear factors GDF3, Dppa3 and the transcription factor Nanog. This cluster of genes lie in the same genomic region, or locus, and this Nanog locus appears to constitute a functional module that is important for pluripotency. Nanog locus gene expression and chromatin structure are both highly dependent on the expression of another pluripotency transcription factor, Oct4. Both Nanog and Oct4 are essential for reprogramming adult cells to a pluripotent state. Study of these factors will be important to help us understand how the property of pluripotency can be reliably conferred upon non-pluripotent cell types. To achieve our goals, we are employing the tools of molecular biology, biochemistry and proteomics. Additionally, we are using conditional gene targeting approaches and RNA interference (RNAi) to engineer new ES cell lines and mouse models.

With less than 5 percent of the mammalian genome responsible for expressing genes, we know that many of the factors vital for pluripotency bind DNA at regulatory elements, known as enhancers, which are far away from known promoter regions. Another topic of study in the laboratory is determining how pluripotency factor bound enhancers bridge long distance interactions within the Nanog locus, and how this regulates gene expression.