The genome is not merely a passive repository of genetic information. Chromosomes are dynamic entities undergoing structural changes that underlie development and cellular differentiation. We are interested in how developmental and environmental cues induce heritable variation in chromatin structure and how these variations regulate developmental potency, cell-fate and gene expression.
The development of the fertilized zygote into a complex organism has traditionally been understood as a unidirectional process, with cells in the embryo becoming gradually more committed to a specific tissue type. However, nuclear transfer experiments have demonstrated that the mammalian egg can relieve the constraints imposed by cellular differentiation and return the nucleus of an adult cell to a totipotent embryonic state. This process has been termed nuclear reprogramming. The primary research focus of our group is to understand the mechanisms by which reprogramming occurs. In particular, we wish to determine the nature of epigenetic information that is reprogrammed (i.e., aspects of DNA methylation and chromatin structure), the times at which reprogramming events occur and the identities of the molecular machinery that accomplish reprogramming.
In addition, we are using nuclear transfer and other approaches to develop human embryonic stem cell lines that carry the genes responsible for human neurodegenerative disease. It is our hope that these cell lines will provide valuable model systems for the in vitro study of these diseases.