Laurie Jackson-Grusby

Research in the Jackson-Grusby laboratory is aimed at understanding the epigenetic basis of disease. In contrast to gene mutations, epigenetic changes refer to the stable silencing of gene expression without a change in the DNA sequence. Gene silencing occurs as a part of normal development, but can also occur abnormally causing cancer and perhaps other age related diseases. Abnormal DNA methylation is also involved in childhood diseases including mental retardation and metabolic disease.

Silencing of genes is associated with a small chemical modification to DNA termed DNA methylation, as well as other chemical modifications to proteins that bind to DNA and affect the packaging of DNA in the nucleus. We have developed mouse models in which the DNA methylation is erased to varying degrees as tools to uncover genes that depend on DNA methylation for proper regulation. One of our near-term goals is to define the set of imprinted genes, those that are normally expressed from a single chromosome determined by the parental inheritance. Using imprinted gene regulation as an assay, we are performing genetic screens to uncover the pathway for maintaining proper regulation of imprinted genes. Loss of imprinting (LOI) is a hallmark of many human cancers, and our LOI mouse model recapitulates a tumor predisposition phenotype. We are additionally studying a mouse brain tumor model to ask whether gene silencing contributes to tumorigenesis in the brain, and whether these effects are exerted in the cancer stem cell compartment of the tumor.