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IU-MSI STEM Initiative

Heather M. O'Hagan

bloomington.medicine.iu.edu/research/heather-o-hagan-lab/

Our lab studies the role of oxidative DNA damage in initiating cancer-specific epigenetic changes.

Inflammation has been linked to cancer formation and progression in part because having a chronic inflammatory disease increases a person's risk of developing cancer. Recent work has demonstrated that inflammation causes alterations in DNA methylation, microRNA expression, and, on a global level, histone marks. Since by definition these epigenetic changes are mitotically heritable and affect gene expression, they likely play a role in establishing disease phenotypes. Changes in DNA methylation, which have been the focus of most studies of the epigenetic responses to inflammation to date, are thought to be a final stage of epigenetic modification. During carcinogenesis, aberrant gains in promoter DNA methylation transcriptionally silence tumor suppressor genes, linking DNA methylation directly to tumorigenesis. However, it is unknown what the mechanisms of targeting and initiation are for these stable cancer-specific epigenetic marks. At sites of inflammation, there are high levels of reactive oxygen species (ROS) that can create oxidative damage. To understand the mechanism of initiation of epigenetic changes, we use both in vitro and in vivo models to link oxidative DNA damage to acute changes in the interaction of epigenetic silencing proteins with each other and the chromatin. Our research findings suggest that one role of oxidative damage in disease may be to initiate epigenetic changes. However, these findings still do not directly link inflammation to epigenetic changes, nor to more permanent disease-specific epigenetic changes. Ongoing projects in my lab address the link between inflammation/oxidative damage and epigenetic changes. Our long-term goal is to gain a better understanding of the mechanism and molecular progression of inflammation-induced epigenetic changes to be able to develop treatments that reverse these epigenetic changes after exposure and therefore prevent disease formation.

Revised: September 20, 2016

Sarah Larson
Program Coordinator
IU-MSI STEM Initiative
Indiana University
set9@indiana.edu
812-855-7463