Serge McGraw, PhD

23 Nov 2017

Contact information

Research interests

  • Embryonic development
  • Prenatal Exposure to alcohol
  • Epigenetic modifications and disturbance
  • Stem cell and cell fate

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.

Members of the laboratory

Elizabeth Elder, MSc
PhD student
elder.elizabeth@icloud.com

Josianne Clavel
PhD student
josianne.clavel@umontreal.ca

Michelle Robb
MSc student
michelle.robb@umontreal.ca

Diego Arturo Camacho Hernandez
MSc student
diego.arturo.camacho.hernandez@umontreal.ca

Charlotte Le Monies de Sagazan
MSc student
charlotte.le.monies.de.sagazan@umontreal.ca

Carlos Michel Mourra Diaz
MSc student
carlos.michel.mourra.diaz@umontreal.ca

Thomas Dupas PhD
Postdoc
thomasdupas.pro@gmail.com

Anthony Lemieux
Bioinformatician
anthony.lemieux@umontreal.ca 

Karine Doiron, PhD
Research associate, Lab Manager
karine.doiron@umontreal.ca

Publications

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Loydie A. Jerome-Majewska, PhD

23 Nov 2017

Contact information

Research interests

  • Labryrinth Layer Development
  • Craniofacial Development

Our laboratory uses the mouse model to identify and characterize expression and function of genes important for normal development. Our placental project focuses on how the chorion and the allantois, two extraembryonic tissues, interact to form the labyrinth placenta. For the craniofacial projects in the laboratory we used reverse genetics, and next generation sequencing to identify genes important for craniofacial development. We identified a number of candidate genes important in vesicular transport and splicing, and are characterizing the role of these genes on morphogenesis and differentiation of the pharyngeal apparatus – the precursor of the face and neck.

Members of the laboratory

Marie-Claude Beauchamp, PhD
Research associate
marie-claude.beauchamp2@mail.mcgill.ca

Wenyang Hou, MSc
PhD student
wenyang.hou@gmail.com

Sabrina Shameen Alam, MSc
PhD student
sabrinalam.cu.bd@gmail.com

Wesley Chan
MSc student
Wesley.chan2@mail.mcgill.ca

Vafa Keser, MSc
PhD student
vafa_salimova@yahoo.com

Sevane Mugashi
Undergraduate student

Maria Tolymbek
Undergraduate student

Publications

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Pierre Leclerc, PhD

23 Nov 2017

Contact information

Research interests

  • Sperm fertilizing competence
  • Sperm/egg interaction
  • Male infertility

My research interests aim at a better understanding of the mechanisms involved in gamete interactions, with a particular emphasis on spermatozoa. The sperm cell must undergo numerous modifications at the membrane and intracellular levels to become capable of interacting with the egg and fertilizing it. Thus, the properties of its plasma and acrosomal membranes will be affected, thereby modulating intracellular ion content, leading to post-translational modifications of several proteins, ultimately resulting in changes in the activity of various enzymes and sperm activities. This post-ejaculatory phenomenon, called capacitation, normally occurs in the female genital tract during the transit of spermatozoa towards the site of fertilization. I am particularly interested in the different intracellular signaling pathways, their control mechanisms during capacitation, and their effects on sperm functions. Furthermore, since the spermatozoon is a highly differentiated cell devoid of transcriptional and translational activities, these intracellular mechanisms control its motility to reach the fertilization site, interact with and fertilize the oocyte, and finally activate the zygote development process.

Another aspect of my research aims to directly study the binding and recognition mechanisms between the spermatozoon and the zona pellucida of the egg by investigating the role of the sperm protein SPAM1 in these phenomena. A better characterization of this protein, the changes in its properties during capacitation, and the importance of these changes for sperm binding to the oocyte are central to my research.

Furthermore, in the context of the agri-food industry where reproduction plays a crucial role and where artificial insemination is a major player, it is essential that spermatozoa are preserved under optimal conditions to ensure reproductive success. Therefore, I am studying the effect of freezing (cryopreservation) on the survival and fertilizing ability of spermatozoa by evaluating ways to improve the procedure.

A better understanding of the mechanisms involved in acquiring fertilizing ability and sperm/egg interactions is important in farm animals where the profitability of the enterprise often depends on the reproductive efficiency of the animal. In humans, the sperm/egg interaction is of particular concern in cases of infertility diagnosis/treatment or in the development of new contraceptive methods. Various research projects are currently underway on these topics in my laboratory.

Members of the laboratory

Tania Laperrière
MSc student
tania.laperriere.1@ulaval.ca

Édith Gosselin
MSc student
edith.gosselin.4@ulaval.ca

Jolianne Bernier
MSc student
jolianne.bernier.1@ulaval.ca

Rohit Kumar Deshmukh
PhD student
rohit-kumar.deshmukh.1@ulaval.ca

Gilles Malherbe
Research professional
gilles.malherbe@crcudequebec.ulaval.ca

Publications

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Julie L. Lavoie, PhD

23 Nov 2017

Contact information

Research interests

  • Activité physique
  • Healthy pregnancy and pathology (hypertensive disorder and diabetes)
  • Animal model and human tissue

PE is diagnosed after 20 weeks of gestation with the onset of hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg) and proteinuria (≥300 mg/24 h). Chronic hypertensive women have a 20-25% risk of developing PE (known as preeclampsia superimposed on chronic hypertension; PESCH). The molecular mechanisms underlying the development of PE are still misunderstood and premature delivery of the foetus is the only treatment available. The renin-angiotensin system (RAS) is postulated to be implicated in the development of PE.

My group has characterized a novel mouse model of PESC. Indeed, mice which overexpress both human angiotensinogen and renin (R+A+), which are hypertensive at baseline, develop spontaneously PESCH-like features as their blood pressure increases, and they develop proteinuria during their pregnancy. This is associated with an increase in AT1 receptor and decrease MasR and ACE2 in placenta and aorta. These modulations may contribute to increase the sensitivity to Ang II as well as decrease both production and sensitivity to Ang 1-7.

While exercise training is well known for its health benefits in the general population, it has also been shown to improve pregnancy outcome during normal gestation. We have recently demonstrated that exercise training can also prevent the occurrence of preeclampsia in mouse models of the disease. Moreover, we have found that the change in RAS observed in the PESCH mouse model can be reduced by exercise training, as we observe an increase in MasR and decrease in AT1 receptor in placenta and aorta. Overall, our project aims at identifying markers of PESCH development and their timing of appearance to allow an earlier diagnostic in patients. We also wish to evaluate the therapeutic potential of both ExT and Ang 1-7 administration in the context of PESCH.

Interestingly, in our recently characterized model of preeclampsia superimposed on chronic hypertension, mice that overexpress both human renin and angiotensinogen (R+A+), we observed that it normalised litter size, which was significantly decreased in the sedentary transgenic mice. Therefore, whereas hypertension or RAS seem to have a negative impact on fertility, exercise training could potentially improve fertility in this model. We therefore wish to test the hypothesis that exercise training restores fertility by modifying the process of ovulation and/or embryo implantation in the R+A+ mice.

Members of the laboratory

Jessica Chemtov
MSc student
jessica.chemtov@umontreal.ca

Sarah Lambert-Roy
MSc student
sarah.lambert-roy@umontreal.ca

Mahsa Maleknia
PhD student
mahsa.maleknia@umontreal.ca

Olivier Chenette-Stewart
PhD student
olivier.chenette-stewart@umontreal.ca

Suzanne Cossette
Research assistant
suzanne.cossette.chum@ssss.gouv.qc.ca

Publications

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Robert S. Viger, PhD

13 Oct 2017

Contact information

Research interests

  • Mammalian sex determination and differentiation
  • Regulation of gonad-specific gene expression
  • Regulation of hormone

My laboratory is interested in defining the transcriptional regulatory pathways that are involved in establishing mammalian sex determination (i.e., the formation of a testis or an ovary) and sex differentiation (i.e., the development of internal and external genitalia and therefore the male or female phenotype). We are also interested in understanding the transcriptional control of gonadal gene expression, especially in the somatic cell types of the testis (Sertoli cell, Leydig cell). Over the past several years, our main focus has been to understand the physiological roles played by members of the GATA family of transcription factors. The GATA family of factors is composed of six zinc finger DNA-binding proteins (named GATA1 to GATA6) that recognize the consensus DNA sequence WGATAR found in the regulatory region of several genes required for the differentiation and/or morphogenesis of numerous vital organs. These factors were first identified as major developmental determinants of both the hematopoietic and cardiac systems.

Today, they are known to be expressed in a wide variety of tissues where they act as critical regulators of developmental- and cell-specific gene expression. This includes multiple endocrine organs such as the pituitary, pancreas, adrenals, and gonads. Using basic molecular biology methodologies (promoter characterization studies) and various cell line models, we have contributed significantly to better understanding what genes and gene networks these factors target and regulate. Indeed, the scope of GATA action has broadened to include early gonadal development, sex differentiation, and steroidogenesis. GATA factors and in particular GATA4 regulate a plethora of genes that play essential roles throughout gonadal ontogeny. These include those expressed early in gonadal development (Sry, Sox9, Amh, Dmrt1) and those acting later in the fetal and adult gonads (Inha, Star, Cyp11a1, Cyp19a1, and many others).We h

ave recent evidence that GATA4 is an essential regulator of steroidogenesis. Interestingly, aberrant GATA function is known to be linked with some human diseases, and we believe that the reproductive system will be no exception. Research into the role of the GATA family of transcription factors in reproductive function has already led to the potential implication of these factors in several human syndromes and/or pathologies such as breast cancer, endometriosis, polycystic ovarian syndrome, and phenotypic sex reversal associated with insufficient AMH expression. Our ultimate goal is to hopefully translate our work into promising new therapies for the treatment and prevention of these pathologies and other diseases that affect reproductive health.

Members of the laboratory

Léa Lafranchise
MSc student
lea.lafranchise.1@ulaval.ca

Marie France Bouchard, PhD
Research assistant
Marie-France.Bouchard@crchudequebec.ulaval.ca

Publications

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Jacques J. Tremblay, MSc, PhD, LLB

13 Oct 2017

Contact information

Research interests

  • Leydig cell differentiation and function
  • Male sexual differentiation
  • Transcription factors and regulation of gene expression

Dr. Tremblay’s research program is at the interface of developmental biology, endocrinology, and cellular and molecular biology. His team studies the molecular mechanisms of male sexual differentiation. Mutations in key genes involved in male sexual differentiation are responsible for an atypical developmental trajectory known as Differences in Sex Development (DSD).

Dr. Tremblay’s team is studying new genes that could help explain certain cases of DSD in humans. In addition, Dr. Tremblay is interested in the differentiation and function of Leydig cells, endocrine cells that produce the steroid hormone testosterone. Inadequate levels of steroid hormones are implicated in many human pathologies, including cancers, PCOS, endometriosis, autoimmune diseases and inflammation. As well as being important for male reproductive health, adequate levels of testosterone are also essential for men’s general health. Understanding how this system functions normally, by studying Leydig cells, will provide essential information that will ultimately enable better diagnosis and treatment of these pathologies.

Although various hormones and signaling molecules have been implicated in male sexual differentiation and Leydig cell differentiation and function, the transcription factors downstream of these pathways remain poorly understood. To date, his team has identified several transcription factors, some never before reported in the gonad or Leydig cells. Some are present exclusively in the male gonad, or at specific times in Leydig cells, while others mark stem Leydig cells. A better understanding of the differentiation of stem Leydig cells residing in the adult testis could enable the development of innovative treatments for men suffering from hypogonadism.

In addition, their work on hormone-induced signaling pathways in Leydig cells has revealed the involvement of two antagonistic kinases; CAMKI stimulates while AMPK is a molecular brake that rapidly shuts down steroid hormone production, which has many clinical implications. Dr. Tremblay’s work involves classical molecular and cell biology, gene editing, animal models, microscopy, proteomics, transcriptomics and bioinformatics.

Members of the laboratory

Laurie Boudreau, BSc
MSc student
laurie.boudreau.3@ulaval.ca

Karine de Mattos, DMV, MSc
PhD student
karine.de-mattos.1@ulaval.ca

Kenley Joule Pierre, MSc
PhD student
kenley-joule.pierre.1@ulaval.ca

Nicholas M. Robert, PhD
Research assistant
Nicholas.Robert@crchudequebec.ulaval.ca

Publications

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Rima Slim, PhD

13 Oct 2017

Contact information

  • 514 934-1934 Ext. 44550
  • rima.slim@muhc.mcgill.ca
  • http://www.mcgill.ca/rslimlab/
  • McGill University Health Center Research Institute
    Glen site,
    EM03210 (office) E012379 (lab)
    1001, boul. Décarie,
    Montréal, Québec H4A 3J1

    Ext. 44550.
    Laboratoire, poste 44519.
    Télécopieur : 514 933-4149 ou 514 933-4673

Research interests

  • Identify new genes responsible for recurrent fetal loss.
  • Elucidate the mechanisms by which the identified genes lead to recurrent fetal loss.
  • Be able to offer DNA diagnosis of recurrent fetal loss and appropriate genetic counseling

The research activities of my group are aimed at the identification of novel genes responsible for recurrent molar pregnancies (pregnancies with no embryos) and miscarriages and the elucidation of the functional roles of the identified genes in these pathologies. This will allow offering the patients new DNA diagnostic tests directed to identify their exact molecular defect and consequently appropriate genetic counseling and assisted reproductive technologies services directed to overcome their exact molecular defects.

Membres du laboratoire

Ankur Saharan
MSc Student
ankur.saharan@mail.mcgill.ca 

Manqi Liang, BSc
MSc student

Maryam Rezaei, MSc
PhD student
maryam28i@yahoo.com

Susmitha Jaganathan, BSc
MSc student
susmitha.jaganathan@mail.mcgill.ca

Publications

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Francois Richard

François Richard, PhD

13 Oct 2017

Contact information

Research interests

  • Role of cyclic nucleotides in ovarian function
  • Role of cyclic nucleotides in mitchondrial function
  • Genomic and epigenomic

My research program investigates the oocyte, better known as “ovule”, but in its immature state. Our team is especially interested in cell signalling since it plays a primordial role in the gamete’s maturation. Even more specifically, we investigate the role of cyclic nucleotide enzyme degradation, namely phosphodiesterases (PDEs). We have made interesting discovering by identifying new families of PDEs found in cumulus cells, some of which seem to be regulated through their association with membrane lipids of the raft family and others which are very sensitive to cAMP regulation.  We are also interested in understanding the dialogue between cumulus cells and the oocyte. We have developed a tools for the functional evaluation of cumulus cells’ response by measuring “Gap junction communication” using fluorophores and photobleaching. Thanks to this approach, we are among world leaders involved in demonstrating the high level of regulation of gap junctions during in vitro maturation. We are very active in our efforts to better understand this regulation. Because energy levels play a decisive role in the oocyte future, we study the KAMP metabolic switch.  We demonstrated the critical impact of this switch at various levels. We also have knowledge transfer projects in collaboration with the industry involved with male and female gametes. Finally, a better understanding of signalling will result in better conditions.

Members of the laboratory

Tiphanie Mérel, MSc
PhD student
tiphanie.merel.1@ulaval.ca

Amel Lounas, MSc
PhD student
amel.lounas.1@ulaval.ca

Publications

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Nicolas Pilon, PhD

13 Oct 2017

Contact information

Research interests

  • Neural crest cell development in health and disease
  • Molecular genetics of sex determination
  • Sex-based differences in nervous system development

Studies in the Pilon’s lab are focused on neurocristopathies, a group of rare genetic diseases in which problems with neural crest cells play a central role. This particular stem cell population generates many different cell types including, among others: peripheral neurons and glia, melanocytes, craniofacial osteoblasts and chondrocytes as well as some specialized cell types of the heart and the inner ear. Because of this large number of derivatives, distinct structures/cell types (isolated or in combination) are affected in each neurocristopathy.

Interestingly, many neurocristopathies also exhibit sex-related issues as seen in Hirschsprung disease (male sex bias in disease incidence) and CHARGE syndrome (subfertility and male-to-female sex reversal). Using mouse models and tissues from human patients, our goal is to decipher the pathogenic mechanisms underlying these diseases with a special focus on their respective sex-related issues.

In the course of our work on neural crest cells, we also developed an interest for polycystic ovary syndrome (PCOS). This interest comes from the incidental generation of a new mouse model via insertional mutagenesis of a previously uncharacterized gene that we are now characterizing in detail.

Members of the laboratory

Alassane Gary, MSc
PhD student
alassanegary@yahoo.ca

Baptiste Charrier,MSc
PhD student
bap.charrier@gmail.com

Elizabeth Leduc, MSc
PhD student
Leduc.elizabeth@courrier.uqam.ca

Marie Lefèvre, MSc
PhD student
Lefevre.marie@courrier.uqam.ca

Mohammad Reza Omrani, MSc
PhD student
omrani.mohammad_reza@courrier.uqam.ca

Nejia Lassoued, MSc
PhD student
nejia_lassoued11@yahoo.fr

Sandrine Girard, BSc
MSc student
Girard.sandrine.3@courrier.uqam.ca

Sanaa Tork, MSc
PhD student
sanaa_t@hotmail.com

Sephora Sallis, MSc
PhD student
Sallis.sephora@courrier.uqam.ca

Sherin Nawaito, PhD
Postdoc fellow
nowatto@gmail.com

Benoit Grondin, PhD
Research associate
b.grondin1@gmail.com

Ouliana Souchkova, MSc
Research assistant
souchkova.ouliana@gmail.com

Rodolphe Soret, PhD
Research associate
rode440@gmail.com

Tatiana Cardinal, PhD
Research associate
cardinal.tatiana@uqam.ca

Publications

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Cristian O’Flaherty, DVM, PhD

13 Oct 2017

Contact information

Research interests

  • Redox signalling and oxidative stress in male reproduction
  • Andrology
  • Gut microbiota and male reproduction

We are interested in the molecular mechanisms that drive the production of mature spermatozoa and their modulation by reactive oxygen species (ROS). The oxidative stress can damage spermatogenesis and sperm maturation, leading to increased defects in the sperm genetic information, motility machinery and the acquisition of fertilizing ability by the spermatozoon. On the other hand, when ROS are produced in low and physiological conditions, they trigger and modulate signalling events that allow the spermatozoon to have fertilizing competence. We are also interested in the relationships between the gut microbiome and male reproduction.

Areas of research:

1) The molecular mechanisms driven by lipid signalling to allow the production of ROS and regulate sperm capacitation.

2) Redox protein modifications in the antioxidant response in mammalian spermatozoa. ROS promote oxidative modifications (thiol oxidation, tyrosine

3) Impact of gut microbiota on the health and disease of the male reproductive system and how gut microbiota can be manipulated to improve male fertility.

Our research is funded by CIHR and the MI4-Pathy Family Foundation.

Members of the laboratory

Elizabeth Pranov
BSc student (Honours program)
elizabeth.pranov@mail.mcgill.ca

Chika Onochie
MSc candidate
chika.onochie@mail.mcgill.ca

Steven Serafini
PhD candidate
steven.serafini@mail.mcgill.ca

Publications

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