Current work focuses on using dietary compounds and chemical inhibitors to reverse inflammation-induced epigenetic changes and reduce tumorigenesis. 2) Inflammation-induced epigenetic alterations create and maintain an altered cellular state that has transformative properties. Colonoids derived from stem cells or crypts isolated from mouse or human colons form budding structures. They lack other cell types and therefore provide an effective approach to study effects of genetic and epigenetic changes in stem and epithelial cells. We are currently using colonoids to understand how inflammation-induced epigenetic alterations prime cells for oncogenic transformation. 3) The mechanism by which chromatin remodelers alter transcription in response to oxidative stress. Oxidative stress activates many downstream signaling pathways. Signaling pathways can alter the function of epigenetic modifiers, which can in turn modify expression of genes that affect signaling pathways. Mutations can also result in aberrant activation of these signaling pathways in cancer cells. We are exploring the connection between activation of signaling pathways, function of epigenetic modifiers, and transcriptional responses. 4) The role of DNA repair proteins and altered DNA damage responses in establishing and maintaining platinum resistance in ovarian cancer.
The overall focus of the O’Hagan lab is to determine how epigenetic factors contribute to cancer initiation, progression and therapy response. We study how the acute chromatin response to inflammation and/or DNA damage results in heritable epigenetic changes during carcinogenesis. We are also interested in how altered epigenetic states promote cancer. We approach our overall research theme from several different directions:
- The mismatch repair protein dependent epigenetic response to oxidative damage.
- Inflammation-induced epigenetic alterations create and maintain an altered cellular state that has transformative properties.
- The mechanism by which chromatin remodelers alter transcription in response to oxidative stress.
- The role of DNA repair proteins and altered DNA damage responses in establishing and maintaining platinum resistance in ovarian cancer.
- Elucidating the role of epigenetic factors in secretory cell specification in colorectal cancer.
