Medical Sciences Seminar. Dr. Heather O'Hagan, Johns Hopkins University School of Medicine. "Oxidative Damage-Induced Epigenetic Changes"
In cancer, aberrant increases in promoter DNA methylation result in the transcriptional silencing of many
genes. However, the mechanism behind the initiation and targeting of such epigenetic silencing events is
unknown. My research focuses on studying how exposure to oxidative stress, a key contributor to
carcinogenesis, can initiate genome-wide epigenetic changes. Previously, I have demonstrated that
exposure to the reactive oxygen species, hydrogen peroxide, results in the formation of a large
epigenetic silencing complex that relocalizes from GC-poor to GC-rich regions of the genome.
Enrichment of this complex at promoter CpG islands results in changes in histone marks, transcription
levels, and, for low expression genes, DNA methylation. My current work encompasses both in vitro
approaches that are more mechanistic and an in vivo model of inflammation-induced tumorigenesis. To
further understand how the epigenetic silencing proteins are recruited to chromatin and form a complex
after exposure to oxidative damage, I am investigating the DNA repair pathway responsible for this
recruitment and protein modifications that may play a role in complex formation and/or function.
Additionally, I utilize a mouse model of inflammation-induced tumorigenesis to study the molecular
progression from acute oxidative-induced epigenetic changes to permanent epigenetic silencing events
during tumorigenesis. Understanding the mechanism of initiation and the timing of cancer-specific
epigenetic changes will allow for the rational development of treatments that reverse epigenetic changes
after exposure to oxidative damage and therefore prevent disease.
- Monday January 28, 2013 04:00 PM
- Monday January 28, 2013 05:00 PM
- Jordan Hall 009
- Medical Sciences
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