Scientific Colloquium
January 28, 2011

Epigenetics is the study of information, heritable during cell division, other than the DNA sequence itself, such as DNA methylation, a covalent modification of cytosine. DNAm is an attractive target for epidemiological study, because it is easily measured in archived samples from pre-existing large patient cohorts. It is now well established from gene-specific studies that epigenetic alterations are important in cancer, and linked to oncogene activation, tumor suppressor gene silencing, and chromosomal instability. We have been taking an integrated approach to catalyze the generalization of gene-specific to genomic epigenetics, and to advance the focus in this field from cancer to common disease generally. Doing this requires an integration of new conceptual, technological, epidemiological and statistical approaches.

Our past work on cancer epigenetics has informed these general studies in surprising ways. For example, a conundrum in common disease research is the missing heritability by GWAS studies, and yet a role for epigenetics has not been generally accepted because it has not been clear how epigenetic marks could be transmitted in a Lamarckian manner over many generations to allow selection. However, we have proposed that epigenetic variation influenced by genetic variants, both stochastic and nonrandom, could help to mediate complex traits. Consistent with this idea, we have identified developmentally important sites of stochastic epigenetic variation in the genome and shown that they are stably linked to important traits such as body mass index. This same idea of stochastic epigenetic variation has also influenced our studies of the cancer epigenome, with some surprising results regarding common mechanisms for altered DNA methylation in cancer, as well as for chromatin organization, with immediate translational implications.

Recent work from our laboratory has identified chromatin modifications that might mediate DNA damage in response to injury. This work could have direct bearing on chemoprotection and even correction of radiation damage during space flight.


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