Researcher

Title

• Associate Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Université de Montréal (2020)
• Researcher, Centre de recherche Azrieli du CHU Sainte-Justine (2015)
• Co-Head, Research Axis - Fetomaternal and Neonatal Pathologies.

• Postdoctoral fellow in epigenetics. Research Institute of the McGill University Health Centre at the Montreal Children's Hospital. Department of Human Genetics, McGill University. Montreal, Canada. 2007-2014
• PhD in biology of reproduction. Department of Animal Sciences, Laval University, Quebec, Canada. 2002-2007.
• MSc in biology of reproduction. Department of Animal Sciences, Laval University, Quebec, Canada. 2000-2001.
• BSc in biochemistry. Laval University, Quebec, Canada. 1997-2000
• Diploma in health sciences. Moncton University. Nouveau-Brunswick, Canada. 1994-1997

Our lab explores the role of epigenetic dysregulation in developmental and neurodevelopmental disorders.

Epigenetic modifications are chemical tags added to DNA or the proteins (histones) that compact and organize it. These modifications help regulate gene activity, turning genes on or off during specific stages of development, without altering the underlying DNA sequence. During embryonic development, cells follow complex programs controlled by dynamic changes in these epigenetic marks. Disruptions in this embryonic epigenetic programming can increase vulnerability to developmental and neurodevelopmental disorders.

Serge McGraw's research program investigates how early epigenetic disruptions lead to such disorders, with three main focus areas:

1. How inherited epigenetic errors affect early embryonic development.
2. How epigenetic errors in brain cells contribute to fetal alcohol spectrum disorder (FASD).
3. How mutations in epigenetic genes (e.g., DNMT3A) disrupt brain cell identity and function in overgrowth and neurodevelopmental disorders, such as Tatton-Brown-Rahman Syndrome (TBRS).

Using genetic and environmental models, including mouse embryos, mouse embryonic stem cells, patient-derived induced pluripotent stem cells (iPSCs), neurons, and 3D cortical organoids, as well as multi-omics sequencing and bioinformatic approaches, our work examines both normal and disrupted epigenetic processes to uncover the mechanisms underlying (neuro)developmental disorders in children. We study how early disruptions in brain-related epigenetic programs can alter cell fate, affect cellular development and function, and lead to neurodevelopmental disorders. Our research aims to pave the way for targeted epigenetic therapies to treat these brain disorders

• Developmental Origin of Health and Disease (DOHAD)
• Fetal Alcohol Spectrum Disorder (FASD)
• Tatton-Brown-Rahman Syndrome (TBRS)
• Rare epigenetic disorders
• Epigenetic modifications (DNA methylation and post-translational modifications of histones)
• Embryonic and placental development
• Embryonic stem cells
• Induced pluripotent stem cells (IPS)
• Next-generation sequencing approaches
• Bioinformatic analyses

Career Summary

Serge McGraw obtained his PhD at Laval University (Quebec), where he worked with Dr. Marc-André Sirard on the factors involved in chromatin remodeling in gametes and embryos. Subsequently, he joined the group of Dr. Jacquetta Trasler at the Research Institute of the McGill University Health Center at the Montreal Children's Hospital where he developed an expertise in developmental biology and in epigenetics. As a postdoctoral fellow, he investigated epigenetic instability associated with epigenetic disruption during embryonic development. His work highlights the importance of the continuous activity of DNMT1, involved in the maintenance of DNA methylation profiles, in the early embryonic days for the future regulation of genes necessary for the nervous system. Dr. McGraw was recruited in 2015 as a researcher at the CHU Sainte-Justine Research Centre and in the Department of Obstetrics and Gynecology at the Université de Montréal, where he is currently an associate professor.

Laboratory

Developmental Epigenetics and Neurodevelopment Lab

Awards and Distinctions

• Knowledge Transfer Award. Réseau québecois en reproduction (RQR), 2024.
• Chercheur-boursier Senior. Fonds de recherche en santé du Québec (FRQS), 2024.
• Knowledge Transfer Award. Réseau québecois en reproduction (RQR), 2022.
• ​Chercheur-boursier Junior 2. Fonds de recherche en santé du Québec (FRQS), 2020.
• Chercheur-boursier Junior 1. Fonds de recherche en santé du Québec (FRQS), 2016.

Publications

1. Elder E, Lemieux A, Legault LM, Caron M, Bertrand-Lehouillier V, Dupas T, Raynal NJM, Bourque G, Sinnett D, Gévry N, McGRAW S. Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells. bioRxiv. 2024 May 7:592204. doi: 10.1101/2024.05.07.592204.
2. Legault LM, Dupas T, Breton-Larrivée M, Filion-Bienvenue F, Lemieux A, Langford-Avelar A, McGRAW S. Sex-specific DNA methylation and gene expression changes in mouse placentas after early preimplantation alcohol exposure. Environ Int. 2024 Oct;192:109014. doi: 10.1016/j.envint.2024.109014.
3. Legault LM, Breton-Larrivée M, Langford-Avelar A, Lemieux A, McGRAW S. Sex-based disparities in DNA methylation and gene expression in late-gestation mouse placentas. Biol Sex Differ. 2024 Jan 6;15(1):2. doi: 10.1186/s13293-023-00577-w.
4. McGRAW S & Kimmins S. Inheritance of epigenetic DNA marks studied in new mouse model. Nature 2023; Mar 21. doi: 10.1038/d41586-023-00708-8
5. Breton-Larrivée M*, Elder E*, Legault LM, Langford-Avelar A, MacFarlane AJ, MCGRAW S. Mitigating the detrimental developmental impact of early fetal alcohol exposure using a maternal methyl donor-enriched diet. FASEB Journal. March 2023; 37:e22829. doi.org/10.1096/fj.202201564R
6. Dupas T, Lauzier B, MCGRAW S. O-GlcNAcylation: the sweet side of epigenetics. Epigenetics Chromatin. 2023 Dec 14;16(1):49. doi: 10.1186/s13072-023-00523-5. Review. PubMed PMID: 38093337; PubMed Central PMCID: PMC10720106.
7. Legault LM, Doiron K, Breton-Larrivée M, Langford-Avelar A, Lemieux A, Caron M, Jerome-Majewska LA, Sinnett D, McGRAW S. Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain. Clinical Epigenetics. 2021 Aug 23;13(1):164. doi: 10.1186/s13148-021-01151-0.