Epigenetic modifications play a significant role in normal development and genome stability and constitute a mechanism of genome adaptation to external stimuli. Dr. Stefanska’s laboratory current research interest is to study how the environment (e.g., diet) impacts cell biology through epigenetic mechanisms. As part of the exposome research, the Stefanska Lab focuses on the functional roles of epigenetic enzymes and chromatin-modifying proteins in the effects on cell biology exerted by dietary polyphenols with different chemical structures. The Stefanska Lab has recently provided the first evidence on mechanisms involved in epigenetic effects of stilbenoid polyphenols in a comprehensive omics study of abnormal human mammary epithelial cells.

 

The Stefanska lab is focused on addressing the following scientific questions:

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1. What are the functional roles of epigenetic enzymes and chromatin-modifying proteins in the effects on cell biology exerted by two distinct dietary polyphenols with known estrogenic activity (phytoestrogens) and uniquely different chemical structures?

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Our goal is to understand how the environment (e.g., diet) impacts cell biology through epigenetic mechanisms. We are addressing the following objectives: a) Determine the functional roles of DNMTs in differential DNA methylation in response to dietary phytoestrogens; b) Establish the interaction between DNA and chromatin-modifying proteins in response to dietary phytoestrogens; c) Determine the mechanistic roles of chromatin-modifying proteins in the epigenetic regulation of transcription in response to dietary phytoestrogens. This will further our understanding of the connection between epigenetic regulation of gene transcription and the phenotype in response to environmental cues (e.g., diet). As nearly all biological processes have an epigenetically regulated component, our findings will broadly impact numerous disciplines in natural sciences, including chemistry and biology.

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2.    Do dietary bioactive compounds reverse epigenetic aberrations underlying inflammation?

 

Existing evidence suggests that at sites of inflammation the release of reactive oxygen species causes DNA damage that induces re-localization of epigenetic proteins and results in DNA methylation changes of associated genes during tumorigenesis. We hypothesize that bioactive compounds target those changes in the DNA methylation patterns, preventing further progression to disease (e.g., cancer).

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3.   Do dietary bioactive compounds act through epigenetic mechanisms to prevent/attenuate  cancer and exert beneficial effects in adjuvant therapy?

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Our hypothesis is that dietary polyphenols (e.g., pterostilbene) impact DNA methylation patterns and thereby gene transcription via modulation of expression and activity of epigenetic enzymes such as TETs and DNMTs. Changes in these enzymes, alter the occupancy of specific protein complexes in gene regulatory regions which determines chromatin structure and as a result gene transcription. Through this mode of action, polyphenols reverse cancer-specific patterns of DNA methylation; they lead to the activation of methylation-silenced tumour suppressor genes and concomitant suppression of demethylation-activated oncogenes and prometastatic genes. We are also exploring if epigenetic mechanisms regulated by polyphenols can sensitize cancer cells to traditional anti-cancer therapeutics.