Researcher

Title

• Head, Research Axis - Immune Disorders and Cancers, CHU Sainte-Justine
• Hematologist Pediatrician, CHU Sainte-Justine
• Clinical Associate Professor, Department of Pediatrics, Université de Montréal

• Hematopoietic stem cells (HSC)
• Chromatin methylation
• Pediatric acute myeloid leukemia (AML)

Long-lived hematopoietic stem cells (HSC) sustain the constant production of all mature cell lineages in the blood system. HSC constitute the critical cellular component of transplantation procedures performed in oncology for high risk malignancies, including leukemia. Nonetheless, factors that dictate HSC fate remain poorly defined, and their isolation and ex vivo culture remain challenging, limiting their clinical applications.

Projects conducted as part of her graduate studies aimed at developing more efficient HSC expansion strategies in vitro. Then, optimisation of screening assays to identify HSC regulators using functional genetics was pursued. Multiple gene candidates could thus be tested simultaneously, using a pipeline of standardized HSC isolation, transduction and transplantation strategies, through overexpression and knockdown studies. Several HSC regulators were identified using these strategies. The main focus of the laboratory is to study the role of chromatin methylation in human HSC biology. Accessibility of the transcriptional machinery to the genetic code is mediated through the concerted actions of chromatin modifying enzymes. The Mll (Mixed Lineage Leukemia) gene, encoding for a histone methyltransferase (of lysine 4 on histone 3, or H3K4) is involved in normal HSC maintenance and mutated in >70% of infant leukemia cases. Once thought to be irreversible, histone methylation is now regarded as a highly dynamic process, since the identification of the histone demethylase LSD1 (KDM1A) in 2004. Previous work identified that JARID1B (KDM5B), an eraser of the H3K4 epigenetic mark, regulates the expression of stemness associated genes, and its knockdown leads to HSC expansion in culture (Cellot S., Hope K.J. et al, Blood 2013). The implication of histone demethylases (HDM) in HSC biology and cancer development is being unraveled, and under active pharmacological scrutiny.

Career Summary

Dr. Sonia Cellot is an assistant professor in the Department of Pediatrics at Université de Montréal and an investigator in the Viral and Immune Disorders and Cancers axis at CHU Sainte-Justine Research Center., She works as a pediatric hematologist in the Hematology-Oncology Division of CHU Sainte-Justine since 2009, where she is responsible for the pediatric acute myeloid leukemia (AML) program. Clinical duties encompass direct patient care, mainly in the HSC transplantation unit, and diagnostic test development as medical advisor in the molecular biology laboratory.

Dr. Cellot is co-investigator with Dr. Josée Hébert of the pediatric branch of the Quebec Leukemia Cell Bank, an initiative aiming to systematically preserve pediatric AML samples for research purposes. She holds a PhD degree in molecular biology from Université de Montréal, where she worked on the identification of nuclear factors that regulate HSC activity. Her research focused on the epigenetic regulators of human HSC and pediatric AML.

Fundings

• CHU Sainte-Justine Foundation
• Cole Foundation
• Fondation Centre de cancérologie Charles-Bruneau
• Fonds de recherche du Québec – Santé (FRQS)
• Terry Fox Research Institute

Presentations

• Cellot S., Hope K.J., Sauvageau M., Chagraoui J., Deneault, É. Mayotte N., MacRae T., Wilhelm B.T, Sauvageau, G. A functional in vivo RNAi screen involving JmjC domain containing candidates unravels Jarid1b as a negative modulator of hematopoietic stem cell self-renewal. American Society of Hematology (ASH) meeting, San Diego, Dec. 2011.
• Pécheux L., Teira P., Bittencourt H., Laramée L., Dormoy-Raclet V., Duval M., Hébert J., Haddad E., Cellot S. GATA2 mutations screening is recommended prior to related transplant for selected cases of pediatric myelodysplastic syndrome (MDS). Canadian Blood and Marow Transplantation Group (GBMTG) annual conferes. Winnipeg, 2013.