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McDonald Lab

Metabolic Reprogramming of Malignant Chromatin

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Investigator / Contact Person Oliver G. McDonald, M.D., Ph.D.

Research Focus

My laboratory investigates how pro-tumorigenic metabolic reactions regulate neoplastic epigenetic outputs in human cancers, especially metastatic pancreatic cancer. We hypothesize that unique metabolic adaptations and epigenetic programs are synergistically co-selected during clonal evolution to promote or even accelerate malignant progression (Franco Torres et al. Cancer and Metastasis Reviews 2023). This hypothesis is supported by our discovery of unusual glucose-fueled biosynthetic reactions (Bechard et al. Oncogene 2018) that reprogram the pancreatic cancer epigenome into a chromatin state that is globally permissive for activation of the metastatic transcriptome (McDonald et al. Nature Genetics 2017). These adaptive metaboloepigenetic programs are self-maintained by positive feedback rather than genetic mutations (Bechard et al. Nature Communications 2020). As such, they are reversible and therefore therapeutically targetable (Smalling et al. Oncogene 2022).

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