Mellissa Mann
Affiliations
Scientist, Division of Genetics & Development, Children’s Health Research Institute
Associate Professor, Departments of Obstetrics and Gynecology and Biochemistry, Schulich School of Medicine & Dentistry, Western University
Scientist, Lawson Health Research Institute
How my research helps children
Infertility has an enormous physical, emotional, and financial toll on society, both nationally and internationally. With the rapid evolution of assisted reproductive technologies (ARTs), it is essential to monitor the consequences of manipulating gametes and embryos in an attempt to safeguard normal development.
Recently, the efficacy and safety of human ARTs have come under intense questioning. Accumulating evidence suggests that children conceived by assisted reproductive technologies are at increased risk of intrauterine growth retardation, premature birth, low birth weight as well as genomic imprinting disorders. Thus, basic science research in an animal model system is required to elucidate the biological mechanisms regulating genomic imprinting in eggs and embryos, and to determine how ART leads to their dysregulation.
The goal of our current research is to determine the effects of hormone treatment administered to mothers on imprint acquisition in oocytes and imprint maintenance in their embryos; to determine the effects of cryopreservation of oocytes and embryos on genomic imprinting; and to determine the effects of embryo culture on genomic imprinting and early development. As the genes investigated in these studies play important roles in early development, and epigenetic defects in these regions lead to the imprinting disorders, Angelman and Beckwith-Wiedemann Syndromes, rigorous and thorough testing of existing assisted reproductive techniques is required to determine their influence on genomic imprinting. Results from these studies will further our understanding of mechanisms that regulate genomic imprinting during oogenesis and early development, and will provide the biologic basis for crucial considerations relevant to the treatment of human infertility by ARTs.
Research
Current Research Activities
My research focuses on epigenetic mechanisms that control gene expression, specifically on genomic imprinting. Genomic imprinting is defined as a mechanism of transcriptional regulation that restricts expression to one parental allele. Imprinting may be envisaged as a multi-step process that begins in the gametes, where epigenetic modifications differentially mark the parental alleles. These marks must then be stably maintained in the developing embryo where they are translated into parental-specific expression. I have four main projects in my lab that are directed towards understanding the regulation of genomic imprinting; Assisted Reproduction: Molecular and Developmental Effects of Gamete and Embryo Manipulation on Genomic Imprinting; The Role of Kcnq1ot1 Noncoding RNA in Imprinted Gene Regulation; Functional Genomic Screen for Epigenetic Modifiers of Genomic Imprinting; Identification and Evolutionary Comparison of Imprinting Centers. We are also investigating Epigenetics of Fetal Growth Restriction. Recent papers from the lab have been published in high impeact journals such as Human Molecular Genetics and Cell Stem Cell, the latter of which was feature as the cover story.
Research Team
Dr. Mann’s lab consists of two graduate students, an MD/PhD student, an undergraduate student, a high school student, and two research technicians. Trainees in Dr. Mann lab have received local and national awards for their work, and have pursued career as an embryologist in Infertility Clinic and a faculty member at Texas A&M University.
Future Research Plans
Future research will explore the effects of cryopreservation of oocytes and embryos on genomic imprinting, and the role of specific epigenetic modifiers in regulation imprinting during gametogenesis and early embryogenesis.
Awards & Grants
Awards & Grants
Funding in support of Identification and Evolutionary Comparison of Imprinting Centers – Awarded by Natural Sciences and Engineering Research Council of Canada (NSERC)
Funding in support of Imprinting Centers and Imprinted Domains – Awarded by The University of Western Ontario Academic Development Fund
Scientist of the Year Award – Awarded by Children's Health Research Institute (CHRI)
Funding in support of Molecular Analysis of Genomic Imprint Maintenance During Embryogenesis – Awarded by Canadian Institute of Health Research (CIHR)
Funding in support of Human Preimplantation Embryos: Effects of assisted reproductive technologies on genomic imprinting – Awarded by Children's Health Research Institute & Department of Obstetrics & Gynaecology, UWO
Funding in support of Effects of Vitrification on Genomic Imprinting – Awarded by Department of Obstetrics & Gynaecology Academic Enrichment Fund
Funding in support of CHRI Training Program in Reproduction, Early Development, and the Impact on Health (REDIH) – Awarded by Canadian Institutes of Health Research (CIHR) Strategic Training Initiative in Health Research
Funding in support of Idenification and Evolutionary Comparison of Imprinting Centers – Awarded by Children's Health Foundation Postdoctoral Fellow Award
Funding in support of The Role of Nucleoporin 107 in Imprinted Gene Regulation – Awarded by Lawson Health Research Institute
New Investigator Award – Awarded by Ontario Women’s Health Council
Young Investigator Award – Awarded by National Institutes of Health, USA
Early Researcher Award – Awarded by Ministry of Research and Innovation
Funding in support of Preimplantation Stage-Specific Analysis of Imprinted Methylation Loss in Mouse In Vitro Cultured Embryos – Awarded by The University of Western Ontario
Funding in support of Collaborative Research and Training Experience, Student Training Resource in Development and Embryology – Awarded by Natural Science and Engineering Research Council of Canada (NSERC)
Funding in support of Bioruptor/Sonicator and circulating waterbath – Awarded by London Regional Cancer Program
Funding in support of Preserving Fertility in the female cancer patient: Establishment of a Oncofertility Team Program – Awarded by Women’s Health Services Development Council
Funding in support of CHRI Training Program in Reproduction, Early Development, and the Impact on Health (REDIH) – Awarded by Canadian Institutes of Health Research
Funding in support of The Role of Kcnq1ot1 noncoding RNA in Imprinted Gene Regulation – Awarded by Lawson Health Research Institute
Funding in support of Characterization of the role of the Kcnq1ot1 non-coding RNA in imprinted gene regulation – Awarded by The University of Western Ontario
Recent Publications
Publications
Chapter 23: Epigenetics and Embryo Culture in Embryo Culture: Advances, Controversies, and Future Considerations (Swain JE, Pool TB and Smith GD (eds.)). Market Velker BA, Denomme MM, Mann MRW. 2011; Humana Press.
Epigenetics in all its glory. Mann, MRW. Development. 2011; 138:5274-5275.
Epigenetics Eh!: A meeting summary of the Canadian Conference on Epigenetics. Rodenhiser DI, Berube NG, Mann MRW. 2011; 6:1265-1271.
Embryonic imprinting perturbations do not originate from superovulation-induced defects in DNA methylation acquisition. Denomme MM, Zhang L, Mann MRW. Fertility and Sterility. 2011; 96:734-738.
Kcnq1ot1 noncoding RNA depletion does not alter imprint maintenance in stem cells. Golding MC, Magri LS, Zhang L, Lalone SA, Higgins MJ, Mann MRW. Development. 2011; 138:3667-3678.
A bidirectional promoter architecture enhances lentiviral transgenesis in embryonic and extraembryonic stem cells. Golding MC, Mann MRW. Gene Therapy. 2011, 18:817-826.
Side-by-side comparison of five commercial media systems in a mouse model system: suboptimal in vitro culture interferes with imprint maintenance. Market-Velker BA, Fernandes AD, Mann MRW. Biology of Reproduction. 2010; 83:936-950.
Domain-specific response of imprinted genes to reduced DNMT1. Weaver JR, Sarkisian G, Krapp C, Mager J, Mann MRW, Bartolomei MS. Molecular and Cellular Biology. 2010; 30:3916-3928.
Multiple epigenetic modifiers induce aggressive viral extinction in extraembryonic endoderm stem cells. Golding MC, Zhang L, Mann MR Cell Stem Cell. 2010 May 7;6(5):457-67
ATRX partners with cohesin and MeCP2 and contributes to developmental silencing of imprinted genes in the brain Kernohan KD, Jiang Y, Tremblay DC, Bonvissuto AC, Eubanks JH, Mann MR, Bérubé NG Dev Cell. 2010 Feb 16;18(2):191-202
Dual effects of superovulation: loss of maternal and paternal imprinted methylation in a dose-dependent manner Market-Velker BA, Zhang L, Magri LS, Bonvissuto AC, Mann MR
Hum Mol Genet. 2010 Jan 1;19(1):36-51
DNA methyltransferase 1o functions at a critical time during development to preclude a profound level of epigenetic variation Cirio, MC, Martel, J, Mann, M, Toppings,M, Bartolomei, M, Trasler, J,Chaillet, JR Developmental Biology 2008 324:139-150
The PcG gene Sfmbt2 is paternally expressed in extraembryonic tissues. Kuzmin A, Han Z, Golding MC, Mann MR, Latham KE, Varmuza S Gene Expr Patterns. 2008 Jan;8(2):107-16
Additional publications
Contact
Phone: 519-685-8500 x 55648
Fax: 519-685-8186
Email: mmann22 [at] uwo [dot] ca
Website: http://publish.uwo.ca/~mmann22
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