Broadening the Search for Cancer Drivers with Chromatin Variants

Mathieu Lupien, PhD
Professor
Department of Medical Biophysics
University of Toronto

Senior Scientist
Princess Margaret Cancer Centre
Ontario Institute for Cancer Research

This conference is hosted by Martin Sauvageau, PhD. This conference is part of the 2024-2025 IRCM conference calendar.

About this conference
The pace of progress in precision medicine for treating cancer patients, which initially centered on using genetic variants such as mutations to identify cancer drivers and match them with effective drug treatments, is now reaching a plateau. To drive precision medicine into a new era of success, alternative strategies must be considered.

Efforts have traditionally focused on genetic variants because DNA is considered the blueprint of cellular identity, being replicated and segregating in a Mendelian manner during division to maintain cell identity. However, this perspective overlooks a crucial aspect: DNA replication occurs alongside chromatin replication, with both the DNA sequence and the associated chromatin states being “passed” to daughter cells. Chromatin, composed of DNA and histone proteins, is the heritable material that undergoes Mendelian segregation, ensuring the fidelity of cellular identity across cell divisions. Chromatin variants play a key role in guiding normal cell state transitions by regulating gene expression and other DNA-templated processes, but they can also drive cellular transformation when they occur at inappropriate locations in the genome.

Thus, a new era of precision medicine involves expanding the focus beyond DNA to include chromatin. In this presentation, you will be introduced to approaches for identifying and characterizing chromatin variants in tumors. We will explore how to analyze these variants to uncover novel cancer drivers, including those outside protein-coding genes, particularly within repetitive DNA sequences. Additionally, you will learn about chromatin editing technologies and how to use them to alter the function of cancer drivers reported from chromatin variants by modifying their chromatin states.

By broadening the scope to include the influence of chromatin variants in identifying cancer drivers, we hope to deepen our understanding of the heritable basis of cancer and pave the way for a new wave of tailored therapies.

About Mathieu Lupien
Dr. Mathieu Lupien is a Senior Scientist at the Princess Margaret Cancer Centre and a Professor at the University of Toronto, with a cross-appointment at the Ontario Institute for Cancer Research. He serves on both the Research Executive and the Research Council on Oncology at the Princess Margaret Cancer Centre.

Dr. Lupien’s research posits that cancer is fundamentally a disease of the chromatin. Among his 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 has also demonstrated that cancer-specific chromatin variants can promote oncogenesis independently of genetic mutations. Furthermore, Dr. Lupien’s research highlights the efficacy of epigenetic therapies targeting chromatin variants to inhibit cancer development and progression.

In recognition of his contributions, Dr. Lupien has received numerous honors, including the Allan Slaight Collaborator Award, the Mona Gauthier Award, and the Canadian Cancer Society Bernard and Francine Dorval Award for Excellence. He is a three-time recipient of the Investigator Award from the Ontario Institute for Cancer Research, a two-time recipient of the Till and McCulloch Discovery of the Year Award, and a co-founder of CoBE. Additionally, Dr. Lupien is a Fellow of the Royal Society of Canada.

Dr. Lupien earned his PhD in Experimental Medicine at McGill University under the mentorship of Dr. Sylvie Mader. He completed postdoctoral training in Medical Oncology as an Era of Hope Fellow at the Dana-Farber Cancer Institute/Harvard Medical School, under the guidance of Dr. Myles Brown, and he has completed executive education (PLDA) at Harvard Business School. Dr. Lupien joined the Princess Margaret Cancer Centre and the University of Toronto in 2012.

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