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JT

Jacquetta M. Trasler, M.D., Ph.D.

James McGill Professor

McGill University

Département: Pediatrics, Human Genetics, Pharmacology & Therapeutics

Montreal Children’s Hospital Research Institute

2300 Tupper Street, Montreal, Quebec, Canada

H3H 1P3

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Téléphone: 514-412-4400, ext 25235

Fax: 514-412-4400

Field of research: 

  • Reproductive and Developmental Epigenetics and Epigenomics
  • Epigenetic Programming in the Germline and Embryo
  • Prenatal and Childhood Origins of Disease
  • Effects of Assisted Reproduction and Infertility on the Offspring
  • Role of Folate and Methyl Donors in Germ Cell and Embryo Development

 

Resume of recent results :

Our long term goal is to better understand normal and abnormal mammalian development. More specifically, we are using molecular and cell biology techniques to study the epigenome and how gene expression is regulated in developing germ cells and embryos and the implications for the resulting offspring. The epigenetic modification, DNA methylation, of specific gene sequences is an important component of a multi-level system that controls gene expression in mammalian cells. DNA methylation is first established during gametogenesis and has been implicated in genomic imprinting. Abnormalities in DNA methylation have been associated with abnormal development, genetic disease and cancer. Recent studies have suggested that epigenetic abnormalities associated with growth and genomic imprinting disorders in the offspring may arise following the use of assisted reproductive technologies. We are testing the hypothesis that the establishment and maintenance of DNA methylation patterns in the germline and early embryo are essential for normal development; thus, altering these patterns is likely to interfere with cellular development and alter the function of germ cells in fertilization and embryo development.

A second interest is to determine the molecular and cellular targets for nutritional and drug effects on developing male germ cells. In collaboration with other investigators, we are developing methods to monitor and prevent drug damage to the germ cells of patients treated for infertility and with anticancer drugs.

 

Laboratory members:

Name

Position

Email address

Josée Martel

Research Associate

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Mylène Landry

Research Assistant

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Donovan Chan

Postdoctoral Fellow

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Patrick Boisvert

Graduate Student (MSc) 

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Justine Garner

Graduate Student (MSc)

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Mena Farag

Graduate Student (MSc)

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Lundi Ly

Graduate Student (MSc)

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List of publications (since 2007)

Kishta O, Adeeko A, Li D, Brawer J, Morales C, Hermo L, Robaire B, Hales BF, Barthelemy J, Cyr DG and Trasler JM. In utero exposure to tributyltin chloride differentially alters male and female fetal gonad morphology and gene expression profiles in the Sprague-Dawley rat. Repro. Toxicol. 23(1):1-11, 2007.

Shovlin TC, Bourc’his D, La Salle S, Trasler JM, Bestor TH, and Walsh CP. Sex-specific promoter regulates Dnmt3L expression in mouse germ cells. Hum. Reprod. 22(2): 457-467, 2007.

Lucifero D, La Salle S, Bourc’his D, Bestor TH and Trasler J.   Coordinate regulation of DNA methyltransferase expression during oogenesis. BMC Dev. Biol.:7:36, 2007.

Oakes CC, La Salle S, Smiraglia D, Robaire B and Trasler J.   Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis in male germ cell development. Dev. Biol. 307(2):368-379, 2007.

Oakes CC, Kelly TL, Robaire B and Trasler JM. Adverse effects of 5-aza-2'-deoxycytidine on spermatogenesis include reduced sperm function and selective inhibition of de novo DNA methylation. J. Pharmacol Exp Ther 322(3):1171-1180, 2007.

La Salle S, Oakes CC, Neaga OR, Bourc'his D, Bestor T H and Trasler JM..   Loss of spermatogonia and wide-spread DNA methylation defects in newborn male mice deficient in DNMT3L, BMC Dev. Biol.:7(1):104, 2007.

Oakes CC, La Salle S, Smiraglia D, Robaire B and Trasler J. A unique configuration of genome-wide DNA methylation patterns in the testis. Proc. Natl. Acad. Sci.: 104(1):228-233, 2007.

Hermo L, Chung S, Gregory M, Smith CE, Wang S, El-Alfy M, Cyr DG, Mitchell GA and Trasler JM. Alterations in the testis of hormone sensitive lipase-deficient mice is associated with decreased sperm counts, sperm motility and fertility. Mol. Reprod. Dev., 75:565-577, 2008.

Smiraglia DJ, Kazhiyur-Mannar R, Oakes CC, Wu Y-Z, Liang P, Ansari T Su J, Rush LJ, Smith LT, Yu L, Liu C, Dai Z, Chen S.-S, Wang S-H, Costello J, Ioshikhes I., Dawson DW, Hong JS, Teitell MA, Szafranek A, Camoriano M, Song F, Elliott R, Held W, Trasler J, Plass C and Wenger R. Restriction Landmark Genomic Scanning (RLGS) spot identification by second generation virtual RLGS in multiple genomes with multiple enzyme combinations. BMC Genomics, 8:446, 2008.

Toppings M, Castro C, Mills PH, Reinhart B, Schatten G, Ahrens ET, Chaillet JR and Trasler JM. Profound phenotypic variation among mice deficient in the maintenance of genomic imprints, Hum. Reprod, 23:807-818, 2008.

Fortier AL, Lopes FL, Darricarrere N, Martel J and Trasler JM. Superovulation alters the expression of imprinted genes in the midgestation mouse placenta. Hum. Mol. Genet., 17:1653-1665, 2008.

Cirio MC, Martel J, Mann M, Toppings M, Bartolomei M, Trasler J and Chaillet JM. DNA methyltransferase 1o functions during preimplantation development to preclude a profound level of epigenetic variation. Dev. Biol. 324(1):139-150, 2008.

Delbès G, Chan D, Pakarinen P, Trasler JM, Hales BF and Robaire B. Impact of the chemotherapy cocktail used to treat testicular cancer on the gene expression profile of male germ cells. Biol. Reprod. 80:320-327, 2009.

Loewy AD, Niles KM, Anastasio N, Watkins D, Lavoie J, Lerner-Ellis JP, Pastinen T, Trasler JM and Rosenblatt DS. Epigenetic modification of the gene for the B12 chaperone MMACHC can result in increased tumorigenicity and methionine dependence. Mol. Genetics Metab. 96:261-267, 2009.

Lopes FL, Fortier AL, Darricarrère N, Chan D, Arnold DR and Trasler JM. Reproductive and epigenetic outcomes associated with aging mouse oocytes. Hum. Mol. Genet, 11:2032-2044, 2009.

Trasler J. Epigenetics in spermatogenesis. Mol Cell. Endocrinology, Vol. 306:33-36, 2009.

Chan D, Cushnie DW, Neaga OR, Lawrance A, Rozen R and Trasler JM. Strain-specific defects in testicular development and sperm epigenetic patterns in 5,10- methylenetetrahydrofolate reductase (MTHFR)-deficient mice. Endocrinology, 151:3363-73, 2010.

Goupil S, La Salle S, Trasler JM, Bordeleau LJ and Leclerc P. Developmental expression of Src-related tyrosine kinases in the mouse testis. J Androl. 32:95-110, 2011.

Niles KM, Chan D, La Salle S, Oakes CC and Trasler JM. Critical period of nonpromoter methylation acquisition during prenatal male germ cell development. PLoS One 6(9): e24156, 2011.

Chan D, Delbès G, Landry M, Robaire B and Trasler J, Chen T, Rozen R, Naumova AK. Epigenetic alterations in sperm DNA associated with testicular cancer treatment. Toxicological Sciences, 125(2):532-43, 2012.

Saferali A, Moussette S, Chan D, Trasler J, Chen T, Rozen R, Naumova AK. DNA methyltransferase 1 (Dnmt1) muration affects Snrpn imprinting in the mouse male germ line. Genome, 55(9):673-82, 2012.

Lee MB, Kooistra M, Zhang B, Slow S, Fortier AL, Garrow TA, Lever M, Trasler JM and Baltz JM. Betaine homocysteine methyltransferase is active in the mouse blastocyst and promotes inner cell mass development. J Biol Chem, 87(39):33094-103, 2012.

Yauk CL, Argueso JL, Auerbach SS, Awadalla P, Davis SR, eMarini DM, Douglas GR, Dubrova YE, Elespuru RK, Glover TW, Hales BF, Hurles ME, Klein CB, Lupski JR, Manchester DK, Marchetti F, Montpetit A, Mulvihill JJ, Robaire B, Robbins WA, Rouleau G, Saughnessy DT, Somers CM, Taylor JG, Trasler J, Waters MD, Wilson TE, Witt KL, Bishop J. Harnessing Genomics to identify environmental determinants of heritable disease. Mutat Res 752(1):6-9, 2013.

Niles KM, Yeh JR, Chan D, Landry M, Nagano MC and Trasler JM. Haploinsufficiency of the parternal-effect gene Dnmt3L results in transient DNA hypomethylation in progenitor cells of the male germline. Hum Reprod 28(2):519-530, 2013.

Delbès G, Chan D, Hales BF, Trasler JM and Robaire B. Selective induction of glutathione S-transferases in round spermatids from the Brown-Norway rat by the chemotherapeutic regimen for testicular cancer. Reprod Toxicol 36:24-32, 2013.

Awards:

  • R. Howard Webster Froundation Award (for research in reproductive medicine and menopause), 2009.
  • Aldo Research Award of Excellence (Pediatrics), 2009.
  • Award for Best Speaker at the 15th European Testis Workshop, Finland, Awarded by the International Network for Young Researchers in Male Infertility, 2008.
  • James McGill Professor Award, 2007-2013.
  • FRSQ "Chercheur Nationaux" Award, 2003-2008.
  • William Dawson Scholar Award, 2002-2007.
  • Young Andrologist Award from the American Society of Andrology, 2001.
  • Prix d'Excellence 2000 from the Foundation for Research into Children's Diseases, 2000.
  • FRSQ Chercheur-Boursier Award ("Senior"), 1998-2002.
  • Medical Research Council of Canada Scientist Award, 1998-2003.
  • FRSQ Chercheur-Boursier ("Junior 2"), 1996-1998.
  • Queen Elizabeth II Research Fund/ Medical Research Council of Canada Scientist Award, 1991-1994.