Department of Pathology
320 Longwood Ave.
Boston, MA 02115
We are interested in understanding how epigenetic control of the genome determines cellular differentiation and development, and how dysregulation of this process causes disease. Our current research addresses three questions regarding epigenetic control in cancer. First, what are the mechanisms involved in aberrant gene silencing in cancer? Second, can epigenetic profiling of tumors be used to uncover new pathways in tumorigenesis? Third, what are the mechanisms of epigenetic control that permit self-renewal of cancer stem cells?
Our research has demonstrated that loss of genomic methylation promotes tumorigenesis through elevated levels of chromosomal instability, however it is essential for tumor progression in cancers that utilize gene silencing. We have further shown that epigenetic changes alone can predispose to tumor formation. We are utilizing mouse and human embryonic stem cell models to globally manipulate the epigenome, and then assess consequent changes in genome organization, gene expression, developmental potency, and tumor formation in vivo.
Jackson-Grusby L, Beard C, Possemato R, Tudor M, Fambrough D, Csankovski G, Dausman J, Lee P, Wilson C Lander E, Jaenisch R. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nature Genetics (2001) 27:31-9.
Holm TM, Jackson-Grusby L, Bambrink T, Yamada Y, Rideout WM3rd, Jaenisch R. Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell (2005) 8:275-85.
Yamada Y, Jackson-Grusby L, Linhart H, Meissner A, Eden A, Lin H, Jaenisch R. Opposing effects of DNA hypomethylation on intestinal and liver carcinogenesis. ProcNatlAcadSci USA (2005) 102:13580-5.
For a complete listing of publications click here.
Last Update: 8/1/2012