Decoding Cancer Through Epigenetics

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Vision

Our laboratory is committed to bringing the best tailored therapy to cancer patients through its innovative discoveries and methodologies in chromatin & epigenetic-based research.


Our five strategic priorities


Our culture

We embrace diversity as our greatest asset. It spurs our creativity, galvanizes our collaborations and drives our innovations.

Our four organizational pillars

"De notre multitude naît notre richesse."

- Elisapie

Why chromatin & epigenetics

“Cancer is a disease of the chromatin, because the genetic contributions to phenotypes are entrusted to the chromatin.” - Mathieu Lupien Ph.D.

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.

Developing epigenetics guided precision medicine against aggressive breast 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

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 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

Finding the epigenetic 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 & 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

"Le merveilleux est la source de l’imaginaire"

Software

Lupien lab github

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Publications

“We embrace diversity as our greatest asset. It spurs our creativity, galvanizes our collaborations and drives our innovations.”

Team


Dr. Mathieu Lupien

"I commit to creating an environment that gets the genius out of the box of those around me and lays the foundation of their professional advancement."

  • Post-doctoral fellow – Dana-Farber Cancer Institute/Harvard Medical School, Dr. Myles Brown alumnus
  • PhD – McGill University, Experimental Medicine, Dr. Sylvie Mader alumnus
  • PLDA – Harvard Business School, Program in Leadership Development 30

Dr. Mathieu Lupien is a Senior Scientist at the Princess Margaret Cancer Centre (PM), an Associate 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. He joined the Princess Margaret Cancer Centre and the University of Toronto in 2012.

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 and is a two times recipient of the Till and McCulloch Discovery of the Year award.

Email: mlupien(at)uhnresearch.ca

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Lab diversity


Lab Members


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Natalia Mukhina

Administrative Assistant

Email: Natalia.Mukhina(at)uhnresearch.ca

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Kip Arlidge

Research Technician

Research interest: Single cell assay development, biotechnology.

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Bansri Patel

Research Technician

Research interest: Assay development, biotechnology.

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Tina Keshavarzian

MSc student (2020/09-present)

Research interest: Epigenetics, Breast cancer, and Computational biology

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Shalini Bahl

MSc student (2020/01-present)

Research interest: Triple-negative breast cancer, GBM, and chemoresistance.

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Jocelyn Chen

PhD Candidate (2019/01-present)

Research interest: Triple-negative breast cancer, chemoresistance.

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James Hawley

PhD Candidate (2017/01-present)

Research interest: Chromatin topology and statistical genomics

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Dr. Giacomo Grillo

Post-doctoral fellow (2018/01-present)

Research interest: Transposable elements in physiology and cancer.

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Dr. Sarina Cameron

Post-doctoral fellow (2017/01-present)

Research interest: Prostate cancer, hypoxia and CRPC.

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Dr. med. Kira Kornienko

Visiting Post-doctoral fellow (2020/11-present)

Research interest: Urooncology, Prostate cancer, Precision medicine, Epigenetics

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Ankita Nand

Bioinformatician (2020/02-present)

Research interest: Data analysis and pipeline development.

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Alumni


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Stanley Zhou

PhD Candidate (2016/01-2020/05)
Current: Arsenal Bio

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Seyed Ali Madani Tonekaboni

PhD Candidate (2016/01-2020/03)
Current: Cyclica

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Parisa Mazrooei

PhD Candidate (2014-2019/09)
Current: Genentech

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Ingrid Kao

MSc student (2015-2017)
Current: Law student

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Aislinn Treloar

MSc student (2013-2016)
Current: Exopharm Ltd, Australia

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Kinjal Desai

PhD Candidate (2011-2016)
Current: Post-doctoral fellow, SickKids

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Surbhi Goel-Bhattacharya

PhD Candidate (2010-2012)
Current: Intellia Therapeutics

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Xiaoyang Zhang

PhD Candidate (2009-2013)
Current: Assistant Professor, Huntsman Cancer Centre, University of Utah, USA

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Richard Sallari

PhD Candidate (2009-2012)
Current: Retired… for now


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Dr. Qin Wu

Post-doctoral fellow (2016/03-2020/12)
Current: Assistant Professor, Tianjin University, China

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Dr. Nergiz Dogan Artun

Post-doctoral fellow (2016/11-2020/10)

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Dr. Bettina Nadorp

Post-doctoral fellow (2019/01-2020/01)
Current: Post-doctoral fellow, New York University

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Dr. Aditi Qamra

Post-doctoral fellow (2018/01-2019/04)
Current: Roche

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Dr. Genevieve Deblois

Post-doctoral fellow (2015/01-2018/11)
Current: Assistant Professor, Université de Montréal

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Dr. Paul Guilhamon

Post-doctoral fellow (2015/01-2018/08)
Current: Post-doctoral fellow, SickKids

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Dr. Alexander Murison

Post-doctoral fellow (2014/09-2018/04)
Current: Post-doctoral fellow, UHN

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Dr. Ken Kron

Post-doctoral fellow (2013/01-2018/06)
Current: Deep Genomics

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Dr. Swneke D. Bailey

Post-doctoral fellow (2012/01-2016/12)
Current: Assistant Professor, McGill University

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Dr. Marco Gallo

Post-doctoral fellow (2012-2015)
Current: Assistant Professor, University of Calgary

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Dr. Nadia M. Penrod

Post-doctoral fellow (2013-2015)
Current: Post-doctoral fellow, University of Pennsylvania

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Dr. Xue Wu

Post-doctoral fellow (2013-2014)
Current: CEO at Geneseeq

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Dr. Luca Magnani

Post-doctoral fellow (2009-2013)
Current: Professor, Imperial College London

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Join us



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.

Outreach

     

     

     


Lupien lab YouTube channel

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Lupien lab playlist

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Collaborators



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Contact

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,
Toronto, ON,
M5G 1L7, Canada
Email: mlupien(at)uhnresearch.ca
Email: Natalia.Mukhina(at)uhnresearch.ca

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