Chromatin · Transcription · DNA damage
O'Hagan Laboratory
Indiana University School of MedicineWelcome to our lab
Mechanisms connecting transcription, DNA damage response and epigenetic change
The O'Hagan laboratory studies how acute chromatin responses to DNA damage and inflammation can become stably inherited epigenetic changes that alter cell identity, promote tumorigenesis and modulate therapy response.
Principal investigator
Heather M. O'Hagan, PhD
Associate Professor, Medical & Molecular Genetics
My group seeks mechanistic links between transcriptional stress, DNA damage responses and epigenetic regulation in cancer.
Full profile →Programmes
Four integrated lines of investigation
01
Transcriptional stress, coupled repair and p53 activation
How does transcriptional blockage and stalled RNA polymerase link DNA damage sensing to p53 activation and cell fate decisions?
02
Damage-induced recruitment of chromatin modifiers and onset of DNA methylation
What molecular events at sites of double-strand breaks or oxidative lesions recruit silencing complexes and how can these lead to de novo DNA methylation at promoters?
03
Inflammation, mismatch repair and initiation of epigenetic changes during tumourigenesis
How do inflammatory exposures cause targeted, heritable epigenetic alterations that predispose to cancer?
04
Epigenetic drivers of therapy resistance and lineage plasticity
Which chromatin regulators and methylation changes sustain therapy‑resistant cell states and permit lineage switching in cancer?
Selected publications
Recent and defining work
2021↗2021↗2011↗2008↗2017↗
LSD1 and aberrant DNA methylation mediate persistence of enteroendocrine progenitors that support BRAF mutant colorectal cancer
Cancer Research
Bacterial-driven inflammation and mutant BRAF expression combine to promote murine colon tumorigenesis that is sensitive to immune checkpoint therapy
Cancer Discovery
Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG islands
Cancer Cell
Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island
PLoS Genetics
Mismatch repair proteins initiate epigenetic alterations during inflammation-driven tumorigenesis
Cancer Research
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