Education & Training
- B.S., Genetics, The University of Western Ontario- 1987
- M.S., Zoology (Genetics), The University of Western Ontario, 1990
- Ph.D., Zoology (Molecular Genetics), The University of Toronto, 1996
Research Interest Summary
Research Interests
Infertility strikes 15% of Americas, with ~7.3 million women receiving medically assisted reproductive technologies (ARTs) in 2010-2015, as they to try to conceive. However, infertility and ARTs can alter epigenetic modifications that are added to chromatin within eggs to ensure proper expression of genes in developing embryos, including genes regulated by genomic imprinting. Genomic imprinting is epigenetic mechanism of transcriptional regulation that restricts expression to one parental copy of a gene. Errors in these mechanisms can lead to genomic imprinting disorders, such as Beckwith-Wiedemann Syndrome and Silver-Russell Syndrome. Research in lab focuses on identifying factors that regulate epigenetic modifications, and how they are altered during ARTs, using mouse gametes, preimplantation embryos, and stem cells.
- Assisted Reproductive Technologies and Genomic Imprinting
Children conceived by assisted reproduction technologies are at increased risk for genomic imprinting disorders. Research in the Mann lab has produced extensive and novel data showing that preimplantation development is a critical period of imprint maintenance that is susceptible to epigenetic perturbation during oocyte and embryo manipulation. Our current work will determine how ARTs perturbs imprint maintenance.
- Imprinted domain regulation during early development
Very little is known about mechanisms that regulate genomic imprinting during early development. W imprinted domainsthat we are currently investigating.
- Role of the Kcnq1ot1 long noncoding in stem cells and early embryos
There is little information on the role of long noncoding RNAs play in establishing imprinting across an imprinted domain during preimplantation development. We are using genetic models to determine the timing of parental allelic silencing of genes within the domain and whether the Kcnq1ot1 noncoding RNA is required for establishment and maintenance of parental allelic silencing.
Representative Publications
Kindsfather AJ, Czekalski MA, Pressimone CA, Erisman MP and Mann MRW. Perturbations in imprinted methylation from assisted reproductive technologies but not advanced maternal age in mouse preimplantation embryos. Clinical Epigenetics, 2019; 11 (1):162. doi: 10.1186/s13148-019-0751-9.
MacDonald WA, Mann MRW. Long noncoding RNA functionality in imprinted domain regulation. PLoS Genetics, 2020; 16(8):e1008930. doi: 10.1371/journal.pgen.1008930. eCollection 2020.
Sachani SS, Landschoot LS, Zhang L, White CR, MacDonald WA, Golding MC, Mann MRW. Nucleoporin 107, 62 and 153 mediate Kcnq1ot1 imprinted domain regulation in extraembryonic endoderm stem cells. Nature Communications, 2018; 9:2795.
White CR, Denomme MM, Tekpetey FR, Feyles V, Power SGA and Mann MRW, High frequency of imprinted methylation errors in donated human preimplantation embryos. Scientific Reports. 2015; 5:17311.
MacDonald WA, Sachani SS, White CR and Mann MRW, 2015, A role for chromatin topology in imprinted domain regulation. Invited Review. Biochemistry and Cell Biology 99:1-13.
MacDonald WA and Mann MRW, 2014, Epigenetic regulation of genomic imprinting from germ line to preimplantation, Molecular Reproduction and Development 81:126-140, Invited Review.
Market Velker BA, Denomme MM and Mann MRW, 2012. Loss of Genomic Imprinting in Mouse Embryos with Fast Rates of Preimplantation Development in Culture, Biology of Reproduction, 86:134-150.
Denomme MM, Zhang L and Mann MRW, 2011, Embryonic imprinting perturbations do not originate from superovulation-induced defects in DNA methylation acquisition. Fertility and Sterility 96:734-738.
Golding MC, Magri LS, Zhang L, Lalone SA, Higgins MJ and Mann, MRW, 2011, Depletion of Kcnq1ot1 non-coding RNA does not affect imprinting maintenance in stem cells, Development, 138:3667-3678.
Golding MC, Zhang L and Mann MRW, 2010, Multiple epigenetic modifiers induce aggressive viral extinction in extraembryonic endoderm stem cells, Cell Stem Cell, 6:457-467.