Mathieu Lupien
Assistant Professor of Genetics
Research Areas: Epigenetics, Genetics, Regulation of Gene Expression
Genome-wide epigenetics/epigenomics of transcriptional regulation in breast cancer
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths in North America. The estrogen receptor alpha (ERα) is a transcription factor central in the development of more than two-thirds of breast tumors. Indeed, through its over-expression in tumor cells, it contributes to the altered gene expression profiles typical of the luminal breast cancer subtypes. By exploiting next-generation sequencing (NGS) technologies, it is now possible to investigate in an unbiased approach various biological processes on a genome-wide scale. Using these NGS technologies applied for ChIP-seq and ncRNA/miRNA/mRNA profiling, research in Dr. Lupien's laboratory focuses on determining how epigenetic/epigenomic events contribute to the ERα-mediated transcriptional reprogramming in breast cancer.
Epigenetic/epigenomic modifications such as DNA methylation, histone post-translational modification (phosphorylation, acetylation, methylation, etc.) as well as small RNA molecules can impact chromatin compaction. This relates directly to transcription programs because closed chromatin (heterochromatin) prevents the recruitment of the transcription machinery required for gene expression, whereas open chromatin (euchromatin) facilitates this process. Therefore, understanding the epigenetic/epigenomic of cancer development and progression offers an under-exploited avenue of research in the development of novel therapeutic interventions as well as diagnostic/prognostic tools. Previous work from Dr. Lupien has revealed specific epigenetic/epigenomic signatures defining functional regulatory elements used by the ERα pathway in breast cancer cell lines (Lupien et al. 2008. Cell). One current theme of research in the laboratory is to establish how these signatures are affected in the course of cancer development and to characterize the mechanisms responsible for their establishment. An additional interest in the laboratory is to identify and define the role of novel epigenetic/epigenomic signatures that potentiate the transcriptional response in breast cancer.
Through his Ph.D. training at McGill University and recent post-doctoral fellowship at the Dana-Farber Cancer Institute (DFCI, Harvard Medical School), Dr. Lupien has contributed to numerous peer-reviewed scientific publications as well as a book chapter on genome-wide chromatin studies. In addition, he received the highly competitive U.S. Army's Department of Defense post-doctoral fellowship for his pioneering research in breast cancer epigenetics/epigenomics at the DFCI. A selection of publications from his most recent work is presented.
Visit the Lupien Lab website.
Publications
Lupien M, Brown M. (2009). Cistromics of hormone-dependent cancer. Endocr Relat Cancer. 16:381-389
Eeckhoute J, Lupien M, Meyer CA, Verzi MP, Shivdasani RA, Liu XS, Brown M. (2009). Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers. Genome Res. 19:372-80
Lupien, M., Eeckhoute, J., Meyer, C.A., Wang, Q., Zhang, Y., Li, W., Carroll, J.S., Liu, X.S. and Brown, M. (2008). FoxA1 translates epigenetic signatures into enhancer driven lineage-specific transcription. Cell. 132: 958-970