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Mailing Address |
Department of Cell & Systems Biology University of Toronto 25 Harbord St. Toronto, ON M5S 3G5 Canada |
Contact Information |
Office phone: 416-978-2759 Office: RW 611A Lab: RW 611 / 612 Lab phone: 416-946-7220 Email: s.varmuza@utoronto.ca URL: |
Research Areas |
Developmental Biology Genetics Molecular Biology |
Research |
Epigenetics, a fairly new field of study describing ancient biochemistry, can be viewed as the molecular intersection of nature and nurture. It involves the study of chromatin, the mix of DNA and proteins that comprise the genome. While the DNA is unchanging from one type of cell to the next, the protein components are highly specific, with many of them working to keep parts of the genome silent. Without epigenetics, we would be puddles of cells. The research in my lab is focussed on the epigenetic process of genomic imprinting in mammals, in which genes “remember” whether they came from the mother or the father, and are either silent or active. The imprinted gene we are currently working on, Sfmbt2, is itself a chromatin protein, and is necessary for viable development of the placenta. It is only expressed from the paternal allele, and when fathers pass on a mutant version, the embryo dies because the placenta fails to develop. SFMBT2 is a chromatin protein, and must regulate genes that are important for placenta development. We are using state of the art genomic and proteomic tools to investigate what parts of the genome are regulated by SFMBT2, and what other proteins it does its job with. Our aim is to define the placenta “Epigenome”, and to describe the features of placental cells that make them different from other cell type. |
Publications |
2014Top |
Positive regulation of TRAF6-dependent innate immune responses by protein phosphatase PP1-γ.Opaluch AM, Schneider M, Chiang CY, Nguyen QT, Maestre AM, Mulder LC, Secundino I, De Jesus PD, König R, Simon V, Nizet V, MacLeod G, Varmuza S, Fernandez-Sesma A, Chanda SK. PLoS ONE 2014;9(2):e89284 pubmed |
PPP1CC2 can form a kinase/phosphatase complex with the testis-specific proteins TSSK1 and TSKS in the mouse testis.MacLeod G, Shang P, Booth GT, Mastropaolo LA, Manafpoursakha N, Vogl AW, Varmuza S. Reproduction 2014 Jan;147(1):1-12 pubmed |
2013Top |
The imprinted polycomb group gene Sfmbt2 is required for trophoblast maintenance and placenta development.Miri K, Latham K, Panning B, Zhong Z, Andersen A, Varmuza S. Development 2013 Nov;140(22):4480-9 pubmed |
The application of proteomic approaches to the study of mammalian spermatogenesis and sperm function.Macleod G, Varmuza S. FEBS J. 2013 Nov;280(22):5635-51 pubmed |
2012Top |
Tandem affinity purification in transgenic mouse embryonic stem cells identifies DDOST as a novel PPP1CC2 interacting protein.MacLeod G, Varmuza S. Biochemistry 2012 Dec;51(48):9678-88 pubmed |
2011Top |
Recent acquisition of imprinting at the rodent Sfmbt2 locus correlates with insertion of a large block of miRNAs.Wang Q, Chow J, Hong J, Smith AF, Moreno C, Seaby P, Vrana P, Miri K, Tak J, Chung ED, Mastromonaco G, Caniggia I, Varmuza S. BMC Genomics 2011;12:204 pubmed |
2010Top |
Loss of protein phosphatase 1c{gamma} (PPP1CC) leads to impaired spermatogenesis associated with defects in chromatin condensation and acrosome development: an ultrastructural analysis.Forgione N, Vogl AW, Varmuza S. Reproduction 2010 Jun;139(6):1021-9 pubmed |
2009Top |
Metakaryotic stem cell lineages in organogenesis of humans and other metazoans.Gostjeva EV, Koledova V, Tomita-Mitchell A, Mitchell M, Goetsch MA, Varmuza S, Fomina JN, Darroudi F, Thilly WG. Organogenesis 2009 Oct;5(4):191-200 pubmed |
Imprinting and extraembryonic tissues-mom takes control.Miri K, Varmuza S. Int Rev Cell Mol Biol 2009;276:215-62 pubmed |
Identification of potentially damaging amino acid substitutions leading to human male infertility.Kuzmin A, Jarvi K, Lo K, Spencer L, Chow GY, Macleod G, Wang Q, Varmuza S. Biol. Reprod. 2009 Aug;81(2):319-26 pubmed |
2008Top |
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 pubmed |
2007Top |
A testis specific isoform of endophilin B1, endophilin B1t, interacts specifically with protein phosphatase-1c gamma2 in mouse testis and is abnormally expressed in PP1c gamma null mice.Hrabchak C, Henderson H, Varmuza S. Biochemistry 2007 Apr;46(15):4635-44 pubmed |
2004Top |
Identification of the spermatogenic zip protein Spz1 as a putative protein phosphatase-1 (PP1) regulatory protein that specifically binds the PP1cgamma2 splice variant in mouse testis.Hrabchak C, Varmuza S. J. Biol. Chem. 2004 Aug;279(35):37079-86 pubmed |
2003Top |
Epigenetics and the renaissance of heresy.Varmuza S. Genome 2003 Dec;46(6):963-7; discussion 968-73 pubmed |
Protein phosphatase 1cgamma is required in germ cells in murine testis.Oppedisano-Wells L, Varmuza S. Mol. Reprod. Dev. 2003 Jun;65(2):157-66 pubmed |
Development to blastocyst is impaired when intracytoplasmic sperm injection is performed with abnormal sperm from infertile mice harboring a mutation in the protein phosphatase 1cgamma gene.Davies T, Varmuza S. Biol. Reprod. 2003 Apr;68(4):1470-6 pubmed |
Increased recombination frequency showing evidence of loss of interference is associated with abnormal testicular histopathology.Varmuza S, Ling L. Mol. Reprod. Dev. 2003 Apr;64(4):499-506 pubmed |