Our laboratory is committed to bringing the best tailored therapy to cancer patients through its innovative discoveries and methodologies in chromatin & epigenetic-based research.
Conduct research on clinically relevant needs and applications.
Identify chromatin & epigenetic determinants of cancer states.
Drive precision medicine using chromatin & epigenetics-informed therapies.
Provide impactful and simple chromatin & epigenetics-based computational and biological methodologies.
Convert our discoveries and methodologies into needed clinical applications.
The research team consists of highly qualified trainees with expertise in computational sciences and in experimental oncology engaged in the design and implementation of state-of-the-art software as well as the adoption and development of the latest chromatin & epigenetic technologies.
We collaborate with national and international clinician-scientists to address the most pressing needs for cancer patients. We partner with scientists across diverse disciplines to conduct research at the leading edge of innovation and transform tomorrow’s care.
The Princess Margaret Cancer Centre is one of the top 5 cancer research centres in the world, and Canada’s largest cancer research and treatment centre. Its infrastructure and resources enable research at the forefront of clinical transformation by accelerating the conversion of basic and translational discoveries into the clinical setting.
Toronto is the fourth largest city in North America and one of the world's most multicultural cities. With a committed discovery district and a growing reputation as the global home of Artificial Intelligence, Toronto is home to the fastest growing tech ecosystem in North America and provides unique opportunities for the commercialization of discoveries. Toronto is the city on hyperdrive, the land of multitude that opens your curiosity and broadens your horizons.
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.
Standard therapy fails for too many breast cancer women. This leads to deadly recurrent tumours. Our goal is to identify weaknesses in recurrent breast tumours based on the chromatin accessibility & epigenetic states of their genome. We then work towards converting those weaknesses into new therapeutic opportunities, inclusive of epigenetic therapy (i.e. drugs specifically designed to change epigenetic states and chromatin accessibility).
Cancer types: Triple-Negative (TNBC) and Proliferative ER-positive Breast Cancer
Cancer is commonly conceived to be a genetic disease. However, not all mutations drive cancer development. Our goal is to discriminate drivers from passenger mutations according to the context of their chromatin accessibility and epigenetic state unique to each tumour. This work is required to find mutations that can guide precision medicine based on genetic markers.
Cancer types: Prostate and Breast Cancer
Tumours are composed of different types of cancer cells that differ in their ability to fuel tumour growth. Cancer stem cells (CSCs), also known as Tumour Initiating Cells are the most dangerous type because of their ability to self-renew and seed new or recurrent tumours. Our goal is to study the chromatin & epigenetic states of CSCs to identify the DNA sequences that allow for self-renewal and tumour initiation. From these DNA sequences we can find the determinants of cancer stemness and use this information to guide the development of new therapies specifically aimed at eliminating the seeding cells.
Cancer types: Leukemia, Glioblastoma, Breast and Prostate Cancer
Dr. Mathieu Lupien is a Senior Scientist at the Princess Margaret Cancer Centre, a Professor at the University of Toronto and holds a cross-appointment with the Ontario Institute for Cancer Research. He serves on the Research Executive and the Research Council on Oncology to the Princess Margaret Cancer Centre.
Dr. Lupien’s research is demonstrating that cancer is a disease of the chromatin. Amongst key discoveries, Dr. Lupien’s research revealed a new type of genomic variation, known as chromatin variants, to pioneer the identification of cancer drivers in the non-coding cancer genome. His work also showed that cancer-specific chromatin variants could support oncogenesis independently of genetic variants (mutations). Finally, Dr. Lupien’s research showed the efficacy of epigenetic therapy that targets chromatin variants to block cancer development and progression. Among other honours, Dr. Lupien is a recipient of the Allan Slaight Collaborator Award, the Mona Gauthier Award, the Canadian Cancer Society Bernard and Francine Dorval Award for Excellence, a three-time recipient of the Investigator Award from the Ontario Institute for Cancer Research, is a two times recipient of the Till and McCulloch Discovery of the Year award and co-founder of CoBE.
Dr. Lupien earned his PhD 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/Harvard Medical School under the mentorship of Dr. Myles Brown followed by a PLDA at Harvard Business School. Dr. Lupien joined the Princess Margaret Cancer Centre and the University of Toronto in 2012.
The Lupien Lab offers a multi-disciplinary team setting. The lab brings together enthusiastic scientists with diverse backgrounds, providing a wide range of perspectives to each research project. This translates into the ideal research environment to push the boundaries of our imagination. Prospective post-doctoral fellows should send their C.V. along with three references to Dr. Mathieu Lupien by email at mlupien(at)uhnresearch.ca
Prospective graduate students (MSc or PhD candidates) interested in joining the Lupien Lab first need to register through the Department of Medical Biophysics, part of the Temerty Faculty of Medicine at the University of Toronto.
Mathieu Lupien Research Laboratory
Princess Margaret Cancer Centre
University Health Network
University of Toronto,
Department of Medical Biophysics
The MaRS Center, PMCRT room 11-706
101 College Street,
M5G 1L7, Canada