Research Summary

Human cell functioning is determined by the genetic code as well as non-genetic factors called epigenetics that include enzymes found in the human body. Epigenetics alter cell function without changing the underlying genetic code. While a number of studies provide evidence that dietary biologically active compounds modulate function of human cells, the underlying mechanisms are unclear. My previous work demonstrates that naturally occurring, food components found in certain fruits influence enzymes in the body that are known to affect epigenetics.  Based at the Food, Nutrition and Health Program of the Faculty of Land and Food Systems at UBC, the goal of my research program is to establish whether and how biologically active compounds present in select foods change the epigenetic make-up in human cells. In our short-term goal we will focus on compounds from blueberries and grapes as they present the most robust effects in our preliminary study and studies by others. We will use molecular biology techniques, including amplification, sequencing, and gene manipulation, to visualize epigenetic modifications and track down enzymes, other proteins and signaling pathways through which these food components act to determine the epigenetic code in human cells. We will address fundamental knowledge gaps in the overarching area of nutrition science, namely epigenetic regulation of cell function in response to dietary compounds. This new knowledge will be critical for revealing distinct elements of human body chemistry that are implicated in the establishment of the epigenetic code. Our findings will benefit farmers and agribusiness leaders by boosting the value and enhancing cultivation of particular varieties of blueberries and grapes that have high content of the studied bioactive compounds. Our results will also address differences in epigenetic effects of compounds with different chemical structure which may be fundamental for the development of analogs with more potent biological activity and indirectly benefit design of preventive and potentially therapeutic compounds for diseases associated with epigenetic aberrations.

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 proteincomplexes 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 dietary exposure to bioactive compounds?

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.

Find more information at http://epigenetics.wixsite.com/stefanskalab

Projects

1) Epigenetic regulation of the NOTCH oncogenic pathway in response to polyphenols from blueberries and grapes (stilbenoids: pterostilbene, piceatannol, resveratrol).

2) Epigenetic mechanisms of polyphenols in prevention of inflammation in a mouse model of colitis and colon cancer.

3) Epigenetic biomarkers of exposure to dietary bioactive compounds.

Collaborations

Building collaborations with the epigenetic community at UBC, including Dr. Lorincz, Dr. Brown and Dr. Kobor Labs. We have already an ongoing collaboration with Dr. Brown on CRISPR technology.

Bio

Education
McGill University, Montreal, Canada, 2013, Postdoctoral Fellow, Cancer Epigenetics
Medical University of Lodz, Lodz, Poland, 2008, PhD, Biomedical Sciences (Nutritional Epigenetics)
Medical University of Lodz, Lodz, Poland, 2003, MPH, Public Health

 

I am an Assistant Professor in Food, Nutrition and Health Program in the Faculty of Land and Food Systems at UBC. I have joined UBC in July this year from Purdue University where I was an Assistant Professor in the Department of Nutrition Science. My area of expertise is nutritional epigenomics and cancer epigenetics. I completed a Master’s in public health and a PhD in nutritional epigenetics at Medical University of Lodz, Poland followed by a postdoctoral training in the Department of Pharmacology and Therapeutics at McGill University in Montreal, Canada. During my doctoral and postdoctoral studies, I explored epigenetic effects of bioactive food components in cancer prevention and support of chemotherapy, and was the first who established the patterns of DNA methylation and gene expression in liver cancer patients and a functional role of DNA methylation differences observed between tumor and normal tissues. My research determined a set of novel cancer candidate genes and potential diagnostic DNA methylation biomarkers. Epigenetic modifications play a significant role in normal development and genome stability and constitute a mechanism of genome adaptation to external stimuli. My laboratory current research interests focus on how diet can lead to health outcomes through modulating the epigenome. My research group investigates the link between bioactive food components, epigenetic alterations and carcinogenesis, and establishes epigenetic biomarkers of exposure to dietary compounds.

Awards

2016: Best Presentation Award, 18th International Conference on Human Genetics and Genomics, December 8-9, 2016, Rome, Italy. Identification of a panel of epigenetic biomarkers for early detection of hepatocellular carcinoma in blood of individuals with liver cirrhosis.

2015: Invited Speaker, Institute of Reproductive and Developmental Biology (IRDB)/Oncology Seminar Series, October 29, 2015, Imperial College London, London, UK. Epigenetic effects of berry polyphenols on oncogenic signalling in breast cancer.

2014: Invited Speaker, 4th International Breast Cancer Prevention Symposium (IBCN), October 16-18, 2014, Purdue University, West Lafayette, IN. Epigenetic mechanisms of dietary polyphenols in cancer prevention.

2014: Invited Speaker, Mead Johnson Pediatric Nutrition Institute Scientific Lecture Series, March 12, 2014, Evansville, IN, USA. Epigenomics: a new bridge between environmental exposures in prenatal/early life and disease onset later in life.

2013:  Invited Speaker, IUNS 20th International Congress of Nutrition, September 15-20, 2013, Granada, Spain. Parallel Symposium (PS4-41): Public health genomics in individualized nutrition.

2013: Principal’s Award for Research Excellence, Medical University of Lodz

2012: McGill MedStar Award for Research Excellence, Faculty of Medicine, McGill University

Publications

Selected Publications

  1. 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)
  2. 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).
  3. 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)
  4. 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).
  5. 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)
  6. Lubecka-Pietruszewska K, Kaufman-Szymczyk A, Stefanska B, Cebula-Obrzut B, Smolewski P, Fabianowska-Majewska K. Sulforaphane alone and in combination with clofarabine epigenetically regulates expression of DNA methylation-silenced tumour suppressor genes in human breast cancer cells. J Nutrigenet Nutrigenomics 2015; 8: 91-101.
  7. Remely M, Stefanska B, Lovrecic L, Magnet U, Haslberger AG. Nutriepigenomics: the role of nutrition in epigenetic control of human diseases. Curr Opin Clin Nutr Metab Care 2015; 18: 328-333. (PMID: 26001651)
  8. Stefanska B, MacEwan DJ. Epigenetics and pharmacology. Br J Pharmacol 2015; 172: 2701-2704. (PMID: 25966315)
  9. Shukeir N*, Stefanska B*, Parashar S, Chik F, Arakelian A, Szyf M, Rabbani SA. Pharmacological methyl group donors block skeletal metastasis in vitro and in vivo. Br J Pharmacol 2015; 172: 2769-2781 (*equal contribution).
  10. Henagan TM, Stefanska B, Fang Z, Navard AM, Ye J, Lenard NR, Devarshi PP. Sodium butyrate epigenetically modulates high fat diet-induced skeletal muscle mitochondrial adaptation, obesity and insulin resistance through nucleosome positioning. Br J Pharmacol 2015; 172: 2782-2798.
  11. Stefanska B, Cheishvili D, Suderman M, Arakelian A, Huang J, Hallett M, Han ZG, Al-Mahtab M, Akbar SMF, Khan WA, Raqib R, Tanvir I, Khan HA, Rabbani SA, Szyf M. Genome-wide study of hypomethylated and induced genes in liver cancer patients unravels novel anticancer targets. Clin Cancer Res 2014; 20: 3118-3132.
  12. Lubecka-Pietruszewska K, Kaufman-Szymczyk A, Stefanska B, Cebula-Obrzut B, Smolewski P, Fabianowska-Majewska K. Clofarabine, a novel adenosine analogue, reactivates DNA methylation-silenced tumour suppressor genes and inhibits cell growth in breast cancer cells. Eur J Pharmacol 2014; 723: 276-87.
  13. Stefanska B, Suderman M, Machnes Z, Bhattacharyya B, Hallet M, Szyf M. Transcription onset of genes critical in liver carcinogenesis and metastasis is epigenetically regulated by methylated DNA binding protein MBD2. Carcinogenesis 2013; 34: 2738-2749.
  14. Stefanska B, Bouzelmat A, Huang J, Suderman M, Hallett M, Han ZG, Al-Mahtab M, Akbar MF, Raqib R, Szyf M. Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes. PLoS One 2013; 8: e68439.
  15. Stefanska B, Karlic H, Varga F, Fabianowska-Majewska K, Haslberger AG. Epigenetic mechanisms in anti-cancer actions of bioactive food components – the implications in cancer prevention. Br J Pharmacol 2012; 167: 279-297. (PMID: 22536923)
  16. Stefanska B, Salamé P, Bednarek A, Fabianowska-Majewska K. Comparative effects of retinoic acid, vitamin D and resveratrol alone and in combination with adenosine analogues on methylation and expression of PTEN tumour suppressor gene in breast cancer cells. Brit J Nutr 2012; 107: 781-790.
  17. Stefanska B, Huang J, Bhattacharyya B, Suderman M, Hallet M, Han ZG, Szyf M. Definition of the landscape of promoter DNA hypomethylation in liver cancer. Cancer Res 2011; 71: 5891-5903.
Office Phone
work phone: 6048222524
Office
248, 2205 East Mall