Research Axis
Fetomaternal and Neonatal Pathologies Axis
Research Theme
Fetal development and prematurity
Address
CHUSJ - Centre de Recherche
Phone
514 345-4931 ext.4268
Epigenetic dysregulations in developmental and neurodevelopmental disorders.
Epigenetic modifications are small chemical groups that can be affixed directly to the genome (DNA), or even to the proteins (histones) involved in the structure and compaction of chromatin. These various modifications provide a means by which a gene can be functionally turned on or off at a specific time during cell development, without altering its DNA sequence. During embryonic development, cells divide and develop according to their own program, a program dictated by a profound reorganization of epigenetic modifications. We believe that any impediment occurring during the establishment of this embryonic epigenetic program may accentuate the vulnerability to unfold various developmental and neurodevelopmental disorders.
Serge McGraw’s research program is focused on studying epigenetic dysregulation in early embryonic development leading to developmental and neurodevelopmental disorders. Specifically, his research is divided into three main areas:
1) Mechanisms of hereditary epigenetic deregulation in early embryonic development.
2) Implication of early embryonic epigenetic dysregulation associated with fetal alcohol spectrum disorder (FASD).
3) Implication of DNMT3A mutations on development and cell specification associated with Tatton-Brown-Rahman syndrome (TBRS).
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. Serge McGraw’s 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.
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.
By combining in vitro models of mouse stem cells and patient-derived pluripotent stem cells, as well as in vivo mouse models, with multi-omics and bioinformatics sequencing approaches, his main research aims to understand how disruptions in the embryonic epigenetic program can alter cell fate and lead to abnormal development and neurodevelopmental disorders.
Laboratory
The Developmental Epigenetics and Neurodevelopment Lab