Research Axis
Fetomaternal and Neonatal Pathologies Axis
Research Theme
Fetal development and prematurity
Address
CHUSJ - Centre de Recherche
Phone
514 345-4931 #4268
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