个人简介

Ph.D. McMaster University, 1985

研究领域

Developmental Biology Genetics Molecular Biology

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.

近期论文

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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 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 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 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 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 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 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