Researchers

Researchers

To come

To come...

Or visit his page on the RQR website

SGirard 

Sylvie Girard, PhD

Professeur-Chercheur

Université de Montréal

Centre de recherche du CHU Ste-Justine

Département d'Obstétrique-Gynécologie

3175, chemin de la Côte Sainte-Catherine
Montréal (Québec)  H3T 1C5

email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Phone: 514 345-4931, poste 2448

Research interests:

Premature birth and intrauterine growth restriction are important pathologies of pregnancy associated with abnormal function of the placenta and having negative effects on the fetus, affecting primarily brain development. My laboratory is interested in understanding the role of inflammation/infection on the maternal-fetal interface, particularly the placenta, leading to these pathological pregnancies and increasing the incidence of neurodevelopmental disorders. Our work focuses on non-pathogenic inflammatory mediators (namely alarmins or damage-associated molecular pattern, DAMPs), the central goal being to determine their role at the maternal-fetal interface and the long-term impact on child development following prenatal exposure to alarmins and inflammation. Globally, our objective is to get a better understanding of the mechanisms linking prenatal inflammation, placental dysfunction and pathological pregnancies in order to develop new diagnostic and therapeutic strategies targeting the placenta to protect the newborn.

Recent results:

We study the possibility to use alarmines, alone or combined with other inflammatory mediators, as diagnostic markers to facilitate the identification of pregnancy at high-risk of pathologies (such as intrauterine growth retardation or premature labor). We recently reported that the levels of several alarmins are elevated in the maternal circulation during pregnancies presenting with at least one of these pathologies, which demonstrate the potential of using alarmins as markers to identify high-risk pregnancies. Alongside this work, we study the effects of alarmins on the placenta since, aside from being potential markers, alarmins can also affects cell function and are a plausible cause of placental dysfunction. Using in vitro/ex vivo technics on the human placenta, we investigated the impact of alarmins on the trophoblast (the main cell type of the placenta) and Hofbauer cells (placental resident fetal macrophage). We determined that alarmins induced inflammation and modulated cell function, primarily in the trophoblast, leading to effects similar to those observed in human pathological pregnancies (ex. decreased hormones production, cell death, etc.). We also use animal models in order to evaluate the long-term effects of prenatal exposure to alarmins and inflammation, with a special interest for neurodevelopmental disorders such as autism and cerebral palsy. The combined use of animal and human models is also use to test new therapeutic strategies, targeting inflammation, to minimise the impact on the placenta and fetus.

Lab members: 

Name

Grade

Email address

Ines Boufaied

Research assistant

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Marie-Eve Brien

MSc student 

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Julia Palacios

MSc student

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Agnes Ditisheim

MSc student

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Co-direction

 

Mathieu Nadeau-Vallée

PhD student This email address is being protected from spambots. You need JavaScript enabled to view it.

Publication list:

Selected publications

Nadeau-Vallée M, Obari D, Quiniou C, Olson D, Girard S, Chemtob S. A critical role of interleukin-1 in preterm labor, Cytokine and Growth Factor Reviews, In press.

Girard S, Sebire G. Transplacental transfer of interleukin-1 receptor agonist and antagonist following maternal immune activation. Am J Reprod Immunol, 2016; 75(1):8-12.

Nadeau-Vallée M, Quiniou C, Palacios J, Hou X, Sanchez M, Madaan A, Leimert K, Boudreault A, Erfani A, Duhamel F, Rivera JC, Olson D, Girard S, Chemtob S. Novel non-competitive interleukin-1 receptor biased ligand prevents infection- and inflammation-induced preterm birth, J Immunol, 2015; 195(7):3402-3415.

Girard S, Heazell AEP, Derricott H, Allan SM, Sibley CP, Abrahams VM, Jones RL. Circulating cytokines and alarmins associated with placental inflammation in high-risk pregnancies. American Journal of Reproductive Immunology, 2014; 72(4):422-434.

Girard S, Murray KN, Rothwell NJ, Metz GAS, Allan SM. Long-term functional recovery and compensation after brain injury. Behavioural Brain Research, 2014; 270:18-28.

Potter JA, Garg M, Girard S, Abrahams VM. Viral ssRNA induces a trophoblast pro-inflammatory and antiviral response in a TLR8-dependent and –independent manner. Biology of Reproduction, In press.

Murray KN, Girard S, Holmes WM, Parkes LM, Williams SR, Parry-Jones AR, Allan SM. Systemic inflammation impairs cerebrovascular function through endothelin-dependent mechanisms in cerebral ischemia. Stroke, 2014; 45(11): 3412-3419.

Girard S, Brough D, Lopez-Castejon G, Giles J, Rothwell NJ, Allan SM. Microglia and macrophages differentially modulate cell death after brain injury caused by oxygen-glucose deprivation in organotypic brain slices. GLIA, 2013; 61(5):813-24.

Girard S, Sebire H, Brochu ME, Briota S, Sarret P, Sébire G. Postnatal administration of IL-1Ra exerts neuroprotective effects following perinatal brain damage. Brain, Behavior and Immunity, 2012; 26(8): 1331-9.

Girard S, Tremblay L, Lepage M, Sébire G. Early detection of placental inflammation by MRI enabling protection by clinically relevant IL-1Ra administration. American Journal of Obstetrics & Gynecology, 2012; 206:358 e1-9.

Girard S, Sébire G, Kadhim H. Proinflammatory orientation of the IL-1 system and downstream induction of MMP-9 in the pathophysiology of human perinatal white matter damage. Journal of Neuropathology and Experimental Neurology, 2010; 69(11): 1116-29.

Girard S, Tremblay L, Lepage M, Sébire G. IL-1 receptor antagonist protects against placental and neurodevelopmental defects induced by maternal inflammation. Journal of Immunology, 2010; 184(7): 3997-4005.

Girard S, Kadhim H, Beaudet N, Sarret P, Sébire G. Developmental motor deficits induced by combined fetal exposure to lipopolysaccharide and early neonatal hypoxia/ischemia: a novel animal model for cerebral palsy in very premature infants. Neuroscience, 2009; 158:673-682.

Roy M, Girard S, Larouche A, Kadhim H, Sébire G. TNF-a system response in a rat model of very preterm brain injuries induced by lipopolysaccharide and/or hypoxia-ischemia. American Journal of Obstetrics & Gynecology, 2009; 201: 493.e1-10.

Awards:

 Fellowship from the CIHR (Canadian Institute of Health Research); 2011-13
Y.W. (Charlie) Loke Award for Early Career Researchers, International Federation of Placenta Associations (IFPA); 2013
Career Development Award, University of Manchester, UK; 2013
Investing in Success Grant, University of Manchester, UK; 2012
Researcher training award, Faculty of Life Sciences, University of Manchester, UK; 2012
Thesis of the year (Life Sciences), Université de Sherbrooke, Qc, Canada; 2011
PhD Scholarship, CIHR (Canadian Institute of Health Research); 2009-12
PhD Scholarship from the FRSQ; 2008-11
PhD award from the Foundation of Stars; 2008

 

To come...

Or visit his page on the RQR website

 


mcgraw serge (2)
 

Serge McGraw, PhD

Assistant professor-researcher
Centre de recherche du CHU Sainte-Justine et Université de Montréal
Department Obstétrique-Gynécologie, Faculté de médecine
3175, Côte Sainte-Catherine, office #A733
Montréal (Québec)  H3T 1C5
This email address is being protected from spambots. You need JavaScript enabled to view it.
Phone: 514 345-4931 ext 4268                                  

 

Research interests:

 Epigenetic Dysregulation and Embryo Development 

Recent results:

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.

 

Publications:

  Siklenka K, Erkek S, Godmann M, Lambrot R, McGraw S, Lafleur C , Cohen T , Xia J , Suderman M , Hallett M, Trasler J, Peters AH, Kimmins S. (2015). Disruption of histone methylation in developing sperm impairs offspring health transgenerationally. Science. 350(6261).

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. 2014. Transient DNMT1 suppression reveals hidden heritable marks in the genome. Nucleic Acids Res. 2015 Feb 18;43(3):1485-97. doi: 10.1093/nar/gku1386.

 Shaffer B, McGraw S, Xiao S, Chan D, Trasler JM, Chaillet JR. 2014. The Dnmt1 intrinsically disordered domain regulates genomic methylation during development. Genetics. 2015 Feb;199(2):533-41. doi: 10.1534/genetics.114.173609.

 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.

 Magnus N, Garnier D, Meehan B, McGraw S, Lee TH, Caron M, Bourque G, Milsom C, Jabado N, Trasler JM, Pawlinski R, Mackman N, Rak J. 2014. Tissue factor expression provokes escape from tumor dormancy and leads to genomic alterations. PNAS. Mar 4;111(9):3544-9.

  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.

 Garner JL, Niles KM, McGraw S, Yeh JR, Cushnie DW, Hermo L, Nagano MC, Trasler JM. 2013. Stability of DNA methylation patterns in spermatogonia under conditions of MTHFR deficiency and methionine supplementation. Biol Reprod. Nov 27;89(5):125.

 Vigneault C, Gravel C, Vallée M, McGraw S, Sirard MA. 2009. Unveiling the bovine embryo transcriptome during the maternal to embryonic transition. Reproduction. Feb;137(2):245-57.

  Vigneault C, McGraw S, Sirard MA. 2009. Spatio-temporal expression of transcriptional regulators in concert with the maternal to embryonic transition during bovine in vitro embryogenesis. Reproduction. Jan;137(1):13-21. Citations: 10, facteur d'impact: 3.55

  McGraw S, Morin G, Vigneault C, Leclerc P, Sirard MA. 2007. Investigation of MYST4 histone acetyltransferase and its involvement in mammalian gametogenesis. BMC Dev Biol. Nov 2;7(1)123.

 McGraw S, Vigneault C, Sirard MA. 2007. Temporal expression of factors involved in chromatin remodeling and in gene regulation during early bovine in vitro embryo development. Reproduction. Mar;133(3):597-608.

 McGraw S, Vigneault C, Tremblay K, Sirard MA. 2006. Characterization of linker histone H1FOO during bovine in vitro embryo development. Mol Reprod Dev. 73(6):692-9.

 Tremblay K, Vigneault C, McGraw S, Morin G, Sirard MA. 2006. Identification and characterization of a novel bovine oocyte-specific secreted protein gene. Gene. 375:44-53.

 Tremblay K, Vigneault C, McGraw S, Sirard MA. 2005. Expression of cyclin B1 messenger RNA isoforms and initiation of cytoplasmic polyadenylation in the bovine oocyte. Biol Reprod. 72(4):1037-44.

 Vigneault C, McGraw S, Massicotte L, Sirard MA. 2004. Transcription factor expression patterns in bovine in vitro-derived embryos prior to maternal-zygotic transition. Biol Reprod. 70(6):1701-9.

 McGraw S, Robert C, Massicotte L, Sirard MA. 2003. Quantification of histone acetyltransferase and histone deacetylase transcripts during early bovine embryo development. Biol Reprod. 68:383-9.

  Robert C, McGraw S, Massicotte L, Pravetoni M, Gandolfi F, Sirard MA. 2002. Quantification of housekeeping transcript levels during the development of bovine preimplantation embryos. Biol Reprod. 67(5):1465-72.

  Robert C, Hue I, McGraw S, Gagne D, Sirard MA. 2002. Quantification of cyclin B1 and p34(cdc2) in bovine cumulus-oocyte complexes and expression mapping of genes involved in the cell cycle by complementary DNA microarrays. Biol Reprod. 67(5):1456-64.

 

Chapitres de livres

  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.

  Robert C, McGraw S, Gagné D, Sirard MA. 2003. Library subtraction and microarray screening to isolate oocyte specific transcripts in the cow. Mammalian Embryo Genomics, Ed: OECD: 57-66.

 

Prix et distinctions :

  • New Collaboration Grant. Réseau Québécois en Reproduction (RQR). 2015
  • Postdoctoral Fellowship. The Montreal Children’s Hospital Research Institute. 2007-2012
  • Postdoctoral Fellowship. Fonds de la Recherche en Santé du Québec. 2009-2011
  •       Postdoctoral Fellowship. Fonds Québécois de la Recherche Nature et Technologies. 2007-2009
  • PhD. Fellowship. Natural Sciences and Engineering Research Council of Canada. 2003-2005
  • PhD. Scholarship. Laval University. 2002-2004
  • PhD. work-study Scholarship. Laval University. 2002
  • 1st prize, oral presentation. Breakthroughs in Reproduction and Development Research Day of the Center for the Study of Reproduction at McGill. 2014.
  • 1st prize, oral presentation. Breakthroughs in Reproduction and Development Research Day of the Center for the Study of Reproduction at McGill. 2013.
  • Short-term visiting scientist award. German Cancer Research Center. Heidelberg, Germany. 2011
  • 1st prize, poster presentation. Chromatin: Structure & Function Meeting. Aruba. 2011
  •       Travel award. Réseau Québécois en Reproduction. 2011
  •       1st prize, oral presentation. McGill Human Genetics Postdoctoral Research Day. 2011
  •       Travel award. Montreal Children’s Hospital Research Institute. 2009
  •       Travel award. Réseau Québécois en Reproduction. 2009
  •       Travel award. Center for the Study of Reproduction. 2009
  •       Travel award. Montreal Children’s Hospital Research Institute. 2008
  • PhD honor roll. Faculty of Graduate Studies, Laval University. 2007
  •       Travel award. Centre de Recherche en Biologie de la Reproduction. 2004
  • Travel award. Centre de Recherche en Biologie de la Reproduction. 2001