Mathieu Lupien

At A Glance

• Research in the Lupien lab focuses on the Epigenetics of cancer, with an emphasis on comprehensive data analytics and mid to high-throughput biological assays.
• The laboratory provides a unique environment where both wet laboratory scientists and computational biologists thrive.
• Data generation relies on next-generation sequencing based assays and new mid to high-throughput profiling technologies
• Data analytics relies on existing software and on in-house algorithmic and software development 

Short Bio

Dr. Mathieu Lupien is a Senior Scientist at the Princess Margaret Cancer Centre (PM), a Professor at the University of Toronto (Canada) and holds a cross-appointment with the Ontario Institute for Cancer Research (OICR). He serves on the Senior Advisory Group and the Research Council on Oncology to the Princess Margaret Cancer Centre.

Dr. Lupien’s research in chromatin & epigenetics has pioneered the study of the non-coding genome to identify determinants of oncogenesis and accelerated the development of chromatin & epigenetic-based precision medicine against cancer.

Dr. Lupien earned his Ph.D. in experimental medicine at McGill University under the leadership of Dr. Sylvie Mader and carried out postdoctoral training in medical oncology as an Era of Hope Fellow at the Dana-Farber Cancer Institute under the mentorship of Dr. Myles Brown followed by an executive education at Harvard Business School Alumni. He joined the Princess Margaret Cancer Centre and the University of Toronto in 2012.

Among other honours, Dr. Lupien is a recipient of the Canadian Cancer Society Bernard and Francine Dorval Award for Excellence, is a two times recipient of the Till and McCulloch Discovery of the Year award, the Investigator Award from the OICR and the Allan Slaight Collaborator of the Year Award.

Research Synopsis

A human consists of trillions of cells with different functions to form different tissues & organs. While genetic differences account for the phenotypic traits unique to individuals, cells from different tissues & organs isolated from one individual each carry a copy of the same genome, a sequence of 6 billion DNA base pairs. Cells across tissues & organs appear and function very differently from one another because each uses different sections of the 6 billion DNA base pairs they carry.

In cells, DNA is packaged with proteins to form chromatin. Chromatin ranges from being “compacted” to “accessible”, the latter associated with sections of the genome driving cell identity. Tissues & organs develop from gradual changes in chromatin accessibility occurring over different DNA base pairs in a stem cell that differentiates into one of many mature cell types. While some DNA base pairs fall in compacted chromatin, others will lie in accessible chromatin to serve as templates for biological functions. Along the way, changes to chromatin accessibility are bookmarked with hundreds of different chemical modifications, such as DNA methylation. These chemical modifications are commonly referred to as “epigenetic” marks. Different combinations of these epigenetic marks over sections of DNA define epigenetic states. Epigenetic states differ across accessible and compacted chromatin and provide information complementary to DNA sequences. DNA base pairs that transition between chromatin accessibility or epigenetic states over development correspond to chromatin variants. Identifying chromatin variants specific to a cell type can therefore identify the genetic basis of a cell’s phenotype.

Cancer is a disease of the chromatin because it arises when a patient’s normal cell acquires the wrong chromatin variants, such as when a normal cell loses control over which sections of the genome are in accessible versus compacted chromatin. Such chromatin variants can originate from inherited or acquired genetic variants, including risk-associated single nucleotide polymorphism (SNPs) or somatic mutations respectively. They can also originate from environmental stresses, such as metabolic stress. Cancer-specific chromatin variants reveal which misused DNA sequences contribute to oncogenesis. Understanding the nature of DNA sequences found in cancer-specific chromatin variants reveals genetic dependencies to oncogenesis and by extension the Achilles heel of cancer needed to guide precise treatment decisions. This is why our research is focused on chromatin and the epigenetics of cancer.

For more information, please visit the Lupien Lab website. 

Recent Publications

1. Hawley JR, Zhou S, Arlidge C, Grillo G, Kron KJ, Hugh-White R, van der Kwast TH, Fraser M, Boutros PC, Bristow RG, Lupien M. (2021). Reorganization of the 3D genome pinpoints non-coding drivers of primary prostate tumors. Cancer Res. 2021 Oct 12:canres.CAN-21-2056-E.2021. doi: 10.1158/0008-5472.CAN-21-2056. Online ahead of print. PMID: 34642184. Senior Responsible Author
2. Takayama N, Murison A, Takayanagi SI, Arlidge C, Zhou S, Garcia-Prat L, Chan-Seng-Yue M, Zandi S, Gan OI, Boutzen H, Kaufmann KB, Trotman-Grant A, Schoof E, Kron K, Díaz N, Lee JJY, Medina T, De Carvalho DD, Taylor MD, Vaquerizas JM, Xie SZ, Dick JE, Lupien M. (2021). The Transition from Quiescent to Activated States in Human Hematopoietic Stem Cells Is Governed by Dynamic 3D Genome Reorganization. Cell Stem Cell, 28(3), 488-501.e10. doi: 10.1016/j.stem.2020.11.001. PMID: 33242413. Senior Responsible Author
3. Deblois G, Madani Tonekaboni SA, Grillo G,  Martinez C, Kao TI,  Tai F,  Ettayebi I,  Fortier A-M,  Savage P,  Fedor AN,  Liu X,  Guilhamon P, Lima Fernandes E, Murison A,  Kuasne H,  Ba-alawi W,  Cescon DW,  Arrowsmith CH, De Carvalho DD, Haibe-Kains B,  Locasale JW, Park M and Lupien M. Epigenetic switch-induced viral mimicry evasion in chemotherapy resistant breast cancer. (2020). Cancer Discovery. doi: 10.1158/2159-8290.CD-19-1493. PMID: 32546577. Senior Responsible Author
4. Michealraj KA , Kumar  SA, Kim LJY, Cavalli FMG, Przelicki D, Wojcik JB, Delaidelli A, Bajic A, Saulnier O, MacLeod G, Vellanki RN, Vladoiu MC, Guilhamon P, Ong W, Lee JJY, Jiang Y, Holgado BL, Rasnitsyn A, Malik AA, Tsai R, Richman CM, Juraschka K, Haapasalo J, Wang EY, De Antonellis P, Suzuki H, Farooq H, Balin P, Kharas K, Van Ommeren R, Sirbu O, Rastan A, Krumholtz SL, Ly M, Ahmadi M, Deblois G, Srikanthan D, Luu B, Loukides J, Wu X, Garzia L, Ramaswamy V, Kanshin E, Sánchez-Osuna M, El-Hamamy I, Coutinho FJ, Prinos P, Singh S, Donovan LK, Daniels C, Schramek D, Tyers M, Weiss S, Stein LD, Lupien M, Wouters BG, Garcia BA, Arrowsmith CH, Sorensen PH, Angers S, Jabado N, Dirks PB, Mack SC, Agnihotri S, Rich JN and Taylor MD. (2020). Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma. Cell. doi: 10.1016/j.cell.2020.04.047. PMID: 32445698.
5. Zhou S, Hawley JR, Soares F, Grillo G, Teng M, Madani Tonekaboni SA, Hua JT, Kron KJ, Mazrooei P, Ahmed M, Arlidge C, Yun HY, Livingstone J, Huang V, Yamaguchi TN, Espiritu SMG, Zhu Y, Severson TM, Murison A, Cameron S, Zwart W, van der Kwast T, Pugh TJ, Fraser M, Boutros PC, Bristow RG, He HH, Lupien M. (2020). Noncoding mutations target cis-regulatory elements of the FOXA1 plexus in prostate cancer. Nat Commun. 11(1):441.  doi: 10.1038/s41467-020-14318-9. PMID: 31974375. Senior Responsible Author
6. Morton AR, Dogan-Artun N, Faber ZJ, MacLeod G, Bartels CF, Piazza MS, Allan KC, Mack SC, Wang X, Gimple RC, Wu Q, Rubin BP, Shetty S, Angers S, Dirks PB, Sallari RC, Lupien M, Rich JN, Scacheri PC. (2019). Functional enhancers shape extrachromosomal oncogene amplification. Cell. 179: 1330-1341. doi: 10.1016/j.cell.2019.10.039. PMID: 31761532.
7. Mazrooei P, Kron KJ, Zhu Y, Zhou S, Grillo G, Mehdi T, Ahmed M, Severson TM, Guilhamon P, Sinnott-Armstrong N, Huang V, Yamaguchi TN, Fraser M, van der Kwast T, Boutros PC, He HH, Bergman AM, Bristow RG, Zwart W and Lupien M. (2019) Cistrome partitioning reveals convergence of somatic mutations and risk variants on master transcription regulators in primary prostate tumors. Cancer Cell. 36:674-689. doi: https: //doi.org/10.1016/j.ccell.2019.10.005. PMID: 31735626. Senior Responsible Author

Graduate Students

Shalini Bahl
Sarah Benamara
Jocelyn Chen
Tina Keshavarzian
Chufan Zhang