Assistant Professor, Food, Nutrition and Health
FNH 248, 2205 East Mall
McGill University, 2013, Post-Doc, Cancer Epigenetics
Medical University of Lodz, Poland, 2008, PhD, Biomedical Sciences (Nutritional Epigenetics)
Medical University of Lodz, Poland, 2003, MPH, Public Health
Epigenetics refers to the molecular events controlling gene expression that are independent of changes in the underlying DNA sequence. These events include DNA methylation, covalent histone modifications, and non-coding RNA-related mechanisms. Epigenetic modifications of DNA, namely DNA methylation, have been shown to contribute to the etiology of chronic diseases with cancer at the forefront. DNA methylation is dynamic and serves as an adaptive mechanism to a wide variety of environmental factors including diet.
My laboratory is focused on addressing the following scientific questions:
- 1) Do dietary bioactive compounds act through epigenetic mechanisms to prevent cancer and exert beneficial effects in adjuvant therapy?
Our hypothesis is that dietary polyphenols (e.g., resveratrol, pterostilbene, piceatannol, and coffee polyphenols) 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.
- 2) Do dietary bioactive compounds reverse epigenetic aberrations underlying initiation of inflammation and inflammation-driven cancer?
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 can prevent cancer development by targeting those changes in the DNA methylation patterns.
- 3) Do changes in epigenetic marks reflect exposure to bioactive compounds and constitute tools of cancer risk prediction and early detection?
We hypothesize that exposure to dietary polyphenols may leave stable marks in human body by inducing changes in DNA methylation patterns. Such molecular markers in easily accessible specimens are needed and should reflect long-term exposures. This will deliver quantitative tools for measuring the intake of bioactive food components in clinical and epidemiological studies.
Please find more information at epigenetics.wixsite.com/stefanskalab
- FNH 351: Vitamins, Minerals, and Health
- FNH 477: Nutrition and Disease Prevention
Megan Beetch, PhD program in Human Nutrition
See Google Scholar for a full list of publications.
Devarshi PP, Jones AD, Taylor EM, Stefanska B, Henagan TM. Quercetin and quercetin-rich red onion extract alter Pgc1α promoter methylation and splice 6 variant expression. PPAR Res 2017; 2017:3235693. (PMID: 28191013)
Stefanska B, MacEwan DJ. Epigenetics and gene expression in cancer, inflammatory and immune diseases. Methods in Pharmacology and Toxicology book series, Springer, January 2017 (Editor).
Choudhury SR, Cui Y, Lubecka K, Stefanska B*, Irudayaraj J*. CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter. Oncotarget 2016; 7: 46545-46556 (*co-senior authorship). (PMID: 27356740)
Lubecka K, Kurzava L, Flower K, Buvala H, Zhang H, Teegarden D, Camarillo I, Suderman M, Kuang S, Andrisani O, Flanagan JM, Stefanska B. Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity. Carcinogenesis 2016; 37: 656-668 (senior author).
Cheishvili D*, Stefanska B*, Yi C, Li CC, Yu P, Arakelian A, Tanvir I, Khan HA, Rabbani SA, Szyf M. A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness. Oncotarget 2015; 6: 33253-33268. (*equal contribution)
- Best Presentation Award, 18th International Conference on Human Genetics and Genomics , 2016
- Invited Speaker, Institute of Reproductive and Developmental Biology (IRDB)/Oncology Seminar Series , 2015
- Invited Speaker, 4th International Breast Cancer Prevention Symposium (IBCN) , 2014
- Invited Speaker, Mead Johnson Pediatric Nutrition Institute Scientific Lecture Series , 2014
- Invited Speaker, IUNS 20th International Congress of Nutrition , 2013
- Principal’s Award for Research Excellence, Medical University of Lodz , 2013
- McGill MedStar Award for Research Excellence, Faculty of Medicine, McGill University , 2012