Researcher

    Serge McGraw , Ph.D.

    serge.mcgraw@umontreal.ca
    Serge McGraw
    Research Axis
    Fetomaternal and Neonatal Pathologies Axis
    Research Theme
    Fetal development and prematurity
    Address
    CHUSJ - Centre de Recherche

    Phone
    514 345-4931 #4268

    Title

    • Head Deputy, Research Axis - Fetomaternal and Neonatal Pathologies, CHU Sainte-Justine
    • Assistant Research Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Université de Montréal

    Education

    • 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

    Career Summary

    Serge McGraw's principal research interests are focused on the harmful developmental outcomes caused by epigenetic instabilities arising from an interruption in DNA methylation maintenance during early embryogenesis. His laboratory aims at understanding how, during embryo development, perturbations in the embryo epigenetic program may be involved in the occurrence of prenatal or after birth developmental disorders.

    Epigenetic Modifications and Embryonic Development

    Epigenetic modifications are small chemical tags which can be added directly on the genome (DNA), or on proteins (histones) that package DNA within chromosomes. These various modifications provide means by which a genetic sequence may be functionally active or inactive at a specific time during cell development, without altering the DNA sequence. During early development, embryonic cells divide and grow according to a program of their own, driven by a major overhaul of epigenetic modifications. We believe that any interference occurring during the establishment of this embryonic epigenetic program may increase the vulnerability to deploy various developmental disorders.

    Epigenetic Dysregulation and Neurodevelopmental Disorders in Children

    In the past few decades, there has been an increase in neurodevelopmental disorders (ex: autism, attention deficit and learning disorders, developmental and intellectual delays) in children. According to numerous studies, exposing the embryo or fetus to harmful environmental insults (ex: poor diet, chemicals, drugs, alcohol) during pregnancy is one of the main causes of this increase. Since these insults can alter the epigenetic landscape, which are heavily reworked in the early embryo, we believe that embryonic epigenetic dysregulation caused by these insults could alter the normal developmental program of the central nervous system and lead to the upsurge of neurodevelopmental disorders. However, essential questions remain unanswered: which epigenetic modifications are likely to be dysregulated in early embryos; which epigenetic regulators, when dysfunctional, could lead to neurodevelopmental disorders; how does epigenetic dysregulation evolve from its embryonic origin to its emergence as a neurodevelopmental disorder after birth? To investigate these questions, Serge McGraw and his research team are using in vitro stem cell models as well as in vivo animal models that contain various epigenetic dysregulation events orchestrated in the embryonic epigenetic program. Through neurotoxic environmental factors and genetic manipulations, these models will provide normal and perturbed epigenetic contexts to finely dissect the epigenetic dysregulation mechanisms associated with neurodevelopmental disorders. His research will significantly deepen our understanding of how early embryonic epigenetic dysregulations of specific brain-related programs may lead to adverse outcomes in children. Understanding the nature of epigenetic dysregulation throughout brain development is crucial if we hope to someday design potent and selective epigenetic treatments for brain disorders.

    Research Topics

    • Epigenetic modifications and interactions
    • Epigenetic dysregulation
    • Embryonic and placental development
    • Embryonic stem cells
    • Prenatal Exposure to environmental insult
    • Developmental Origins of Health and Disease
    • Next-generation sequencing based approaches

    Awards and Distinctions

    • Fellowship, Team Reasearch Project, Fonds de recherche du Québec – Nature et technologies (FRQNT), 2017
    • New Collaboration Grant. Réseau Québécois en Reproduction (RQR). 2015
    • Postdoctoral Fellowship award. The Montreal Children’s Hospital Research Institute. 2007-2012
    • Postdoctoral Fellowship award. Fonds de la Recherche en Santé du Québec (FRQS). 2009-2011
    • Short-term visiting scientist award. German Cancer Research Center (DKFZ). Heidelberg, Germany. 2011
    • Postdoctoral Fellowship award. Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT). 2007-2009
    • PhD honor roll. Faculty of Graduate Studies, Laval University. 2007
    • PhD. Fellowship award. Natural Sciences and Engineering Research Council of Canada (NSERC). 2003-2005

    Presentations

    • Chronologie et évolution de perturbations épigénétiques induites pendant le développement embryonnaire précoce: Modélisation de troubles développementaux. Axe de Recherche Pathologies Fœtomaternelles et Néonatales. Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine. Montréal. 2015
    • Implication des Dérèglements Épigénétiques prénataux dans l'émergence de Troubles Développementaux. Département d'Obstétrique-Gynécologie, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine. Montréal. 2014
    • Transient DNMT1 suppression reveals hidden heritable marks in the genome 2nd Canadian Conference on Epigenetics: Epigenetics, Eh! London. 2014
    • Transient DNMT1 suppression reveals hidden heritable marks in the genome. Breakthroughs in Reproduction and Development Research Day. Université McGill. 2014
    • Le dérèglement épigénétique et l'origine développementale de la santé et des maladies. Axe de Recherche Pathologies Fœtomaternelles et Néonatales. Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine. Montréal. 2014
    • Sustained loss of DNA methylation at imprinted-like loci following transient Dnmt1 deficiency in mouse ES cells. Breakthroughs in Reproduction and Development Research Day. Université McGill. 2013
    • L'interdépendance des facteurs épigénétiques: implication durant le développement embryonnaire et la santé reproductive. Département d’Obstétrique-Gynécologie. Centre Hospitalier de l'Université Laval. 2013
    • Epigenetic instability following perturbation of DNA methylation patterns. Hot Topics in Reproduction. Université McGill. 2012
    • Transient Dnmt1 deficiency in mouse embryonic stem cells results in aberrant DNA methylation patterns at imprinted and non-imprinted loci 4e Symposium du Réseau Québécois en Reproduction. Montréal.. 2011
    • Epigenetic instability following perturbation of DNA methylation patterns. Epigenomics and Cancer Risk Factors Division. German Cancer Research Center (DKFZ). Allemagne. 2011
    • Loss of Dnmt1o disrupts imprinted X-chromosome inactivation and placental integrity in females. Journée de la Recherche Postdoctorale. Université McGill. 2011
    • DNMT1o and the role of the early embryo in maintaining and transmitting epigenetic patterns to the progeny. Hot Topics in Reproduction. Université McGill. 2011
    • Deficiency in maternal DNMT1o disrupts global DNA methylation and imprinted X chromosome inactivation in extra-embryonic tissues. Breakthroughs in Reproduction and Development Research Day of the Centre for the Study of Reproduction at McGill. Université McGill, Montréal. 2010
    • L’épigénome et les fonctions reproductrices. 17e Rencontre Hivernale des Biologistes en Reproduction du Québec. Centre de Recherche en Reproduction. 2009
    • Études de facteurs impliqués dans le remodelage de la chromatine chez les gamètes et les embryons bovins. Défense de thèse. Université Laval. 2007
    • Chromatin remodeling in gametes and embryos. Département des Sciences de l’Agriculture et Nutrition. Université de l’Alberta. 2006
    • Le remodelage de la chromatine dans les gamètes. Département de Biologie. Université de Moncton. 2006
    • Le secret le plus précieux de l’ovule: la recette de la totipotence.13e Rencontre Hivernale des Biologistes en Reproduction du Québec. Centre de Recherche en Reproduction. 2005
    • Caractérisation de H1FOO dans l’ovule et l’embryon bovin. 72e Rencontre annuelle de l’Association Francophone pour le Savoir (ACFAS). Université du Québec à Montréal. 2004
    • Quantification of histone acetyltransferase transcripts in early bovine embryo development. Rencontre Roche Canadienne des Utilisateurs de Light Cycler. Montréal. 2002

    Publications

    • McGraw S, Zhang JX, Farag M, Chan D, Caron M, Konermann C, Oakes CC, Mohan KN, Plass C, Pastinen T, Bourque G, Chaillet JR, Trasler JM. 2015. Transient DNMT1 suppression reveals hidden heritable marks in the genome. Nucleic acids research. 43(3): 1485-97.
    • Fortier AL, McGraw S (co-first), Lopes FL, Niles KM, Landry M, Trasler JM. 2014. Modulation of imprinted gene expression following superovulation. Mol Cell Endocrinol. May 5;388(1-2):51-7.
    • McGraw S, Shojaei Saadi HA, Robert C. 2013. Meeting the methodological challenges of studying the embryonic epigenome. Mol Hum Reproduction. Dec;19(12):809-27.
    • McGraw S, Oakes CC, Martel J, Cirio MC, de Zeeuw P, Mak W, Barlolomei MS, Chaillet JR, Trasler JM. 2013. Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females. Plos Genetics. Nov;9(11):e100387.
    • McGraw S & Trasler JM. 2013. Oocyte epigenetics and the risks for imprinting disorders associated with assisted reproduction. Biology & Pathology of the Oocyte 2nd Edition. Cambridge University Press. Online Publication October 10th.
 

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