Vision
Conquer cancer by treating it as an epigenetic/chromatin disease.
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"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.
Finding the determinants of cancer cell states from chromatin variants
Tumours are composed of cancer cells in different states, that differ in their ability to propagate. 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
Defining how chromatin state impact the function of mutations in cancer
Cancer is commonly conceived to be a genetic disease, with mutations taking centre stage. However, not all mutations drive cancer development. Our goal is to identify cancer driver DNA elements, taking into account the mutational load within chromatin state defined DNA elements, such as regulatory elements, gene regulatory plexus or cistromes. This work is required to find mutations that can guide precision medicine based on genetic markers.
Cancer types: Prostate and Breast Cancer
Developing chromatin-guided targeted therapy against aggressive forms of cancer
Standard therapy fails for too many cancer patients and leads to deadly recurrent tumours. Our goal is to identify weaknesses in recurrent tumours based on chromatin variants and characterize their epigenetic and genetic composition. Based on their composition, we then identify weaknesses to therapies by repurposing existing drugs or guiding the design of new agents.
Cancer types: Triple-Negative (TNBC) and Proliferative ER-positive Breast Cancer
