Dr. Mathieu Lupien is a Senior Scientist at the Princess Margaret Cancer Centre, an Associate Professor at the University of Toronto 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 is a world-renowned cancer scientist. His research in chromatin and epigenetics has pioneered the study of the noncoding genome and accelerated the development of chromatin and epigenetic-based precision medicine against cancer.

Among other honours, Dr. Lupien is a recipient of the Investigator Award from the OICR, the Canadian Cancer Society Bernard and Francine Dorval Award for Excellence, the Rising Star in Prostate Cancer Research award from Movember, the Mona Gauthier Award, and is a two times recipient of the Till and McCulloch Discovery of the Year award.

Genetic contributions to a given phenotype is entrusted to the chromatin, reflected in its epigenetic state. That is why our research is focused on chromatin and the epigenetics of cancer.” —Mathieu Lupien PhD, PLDA

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

In cells, DNA is packaged with proteins to form chromatin that regulates access to base pairs according to its degree of accessibility. Specifically, chromatin ranges from being “compacted” to “accessible”, the latter associated with DNA base pairs driving cell identity. Tissue and organ develop from gradual changes in chromatin accessibility occurring over different DNA base pairs in a stem cell that differentiated 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, defining their epigenetic states. These epigenetic states differ across accessible and compacted chromatin and provide information complementary to DNA. What distinguishes cells found across tissues and organs is a combination of DNA base pairs found in accessible versus compacted chromatin and their epigenetic states.

Tumours differ from normal tissues and organs because the DNA base pairs found in accessible versus compacted chromatin and their epigenetic states differ between cancer versus normal cells. This stems from mutations and/or environmental exposures, forcing cells out of their normal differentiation path. Instead, cells end in an undifferentiated, more stem-like state that enables sustained growth over time. By studying the DNA base pairs found in accessible chromatin and their epigenetic state, we can identify the drivers of oncogenesis, both for the development and the progression of cancer. This is why our research is focused on chromatin and the epigenetics of cancer.

The Lupien lab research program is founded on three themes:

1. Developing epigenetics-guided precision medicine against aggressive breast cancer
Standard therapy fails for too many women affected by breast cancer. This leads to deadly recurrent tumours. Our goal is to identify weaknesses in recurrent breast tumours based on the chromatin accessibility and 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

2. Defining which mutations are genetic drivers of oncogenesis
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 the chromatin accessibility and epigenetic state that is 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

3. Finding the chromatin determinants of stemness and tumour initiating potential
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 and epigenetic states of CSCs to identify the DNA sequences that enable 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

Related Links

For a list of Dr. Lupien's publications, please visit PubMed, Scopus or ORCID.

Associate Professor, Department of Medical Biophysics, University of Toronto
Investigator II, Ontario Institute for Cancer Research