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Principal Investigators

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Dr Dixie Mager — PhD

Distinguished Scientist

Dixie-Magerx1

Laboratory Contact

Liane Gagnier

Cancer Research Technologist
  604-675-8000 Ext. 7770 (Mager Lab) / Ext. 7762 (Stirling Lab)

Admin Contact

Christine Kelly

Senior Secretary
  604.675.8127
Overview
Research Interest
Publications
Lab Members
Links
  • Gene regulation and epigenetics
  • Transposable elements, Bioinformatics

Our laboratory uses molecular and cellular biology approaches, coupled with bioinformatics, to address questions in gene regulation, genomic stability and malignancy. The primary focus of our laboratory is to determine how transposable elements influence gene regulation and the epigenetic and genetic stability in normal and cancer cells.
Nearly half of the human genome is  composed of sequences related to transposable elements (TEs). These elements, which include endogenous retroviruses (ERVs), have colonized our genome during evolution and some are still mobile - causing cancer in mice and genetic disease in humans and animals.  The epigenetic state of TEs is often altered in cancer, a reflection of global epigenetic abnormalities associated with malignancy. Ongoing or future projects include: i) Characterizing genes that use TE-derived regulatory signals; ii) Elucidating the complex relationship between epigenetic silencing of TEs and the resultant effects on gene expression; iii) Using patterns of genomic TE distributions to uncover novel aspects of gene regulation; iv) Determining the potential pathogenic role of epigenetic activation of ERVs and other TEs in human lymphomas and other cancers; and v) Investigating the activity of ERVs in induced pluripotent stem (ips) cells and potential ramifications of such activity for cell-based therapies.

 

 

Selected Publications

2016

Babaian A, Romanish MT, Gagnier L, Kuo L, Karimi MM, Steidl C & Mager DL. Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma.  Oncogene  35: 2542-2546, 2016.  View Abstract

Gerdes P, Richardson SR, Mager DL & Faulkner GJ. Transposable elements in the mammalian embryo: pioneers surviving through stealth and service. Genome Biol. 17:100, 2016. View Abstract

Izsvak Z, Wang J, Singh M, Mager DL & Hurst LD. Pluripotency and the endogenous retrovirus HERVH: Conflict or serendipity?  Bioessays 38: 109-117, 2016. View Abstract

Rebollo R & Mager DL. Methylated DNA immunoprecipitation analysis of mammalian endogenous retroviruses. Methods Mol Biol 1400: 377-385, 2016.  View Abstract

2015

Mager DL & Stoye JP.   Mammalian endogenous retroviruses. MicrobiolSpec 3 MDNA3: 1-20, 2015. View Abstract

2014

Juriloff DM, Harris MJ, Mager DL & Gagnier L. Epigenetic mechanism causes Wnt9b deficiency and nonsyndromic cleft lip and palate in the A/WySn mouse strain.  Birth Defects Res A Clin Mol Teratol  100:772-788, 2014. View Abstract

Rita-Frances-PNAS

Lock FE, Rebollo R, Miceli-Royer K, Gagnier L, Kuah S, Babaian A, Sistiaga-Poveda M, Lai CB, Nemirovsky O, Serrano I, Steidl C, Karimi MM & Mager DL. A distinct isoform of FABP7 revealed by screening for retroelement activated genes in diffuse large B-cell lymphoma.  Proc Natl Acad Sci USA 111: E3534-E3543, 2014. View Abstract

 

2013

Zhang Y, Babaian A, Gagnier L & Mager DL.  Visualized computational predictions of transcriptional effects by intronic endogenous retroviruses.  PLoS One  8: e71971, 2013. View Abstract

2012

Rebollo R, Miceli-Royer K, Zhang Y, Farivar S, Gagnier L & Mager DL. Epigenetic interplay between mouse endogenous retroviruses and host genes. Genome Biol 13: R89, 2012. View Abstract

Rebollo R, Romanish MT & Mager DL. Transposable elements: An abundant and natural source of regulatory sequences for host genes.  Annu Rev Genet  46: 21-42, 2012. View Abstract

LaiBC & Mager DL. Role of runt-related transcription factor 3 (RUNX3) in transcription regulation of natural cytotoxicity receptor 1 (NCR1/NKp46), an activating natural killer (NK) cell receptor.  J Biol Chem 287: 7324-7334, 2012. View Abstract

Zhang Y & Mager DL. Gene properties and chromatin state influence the accumulation of transposable elements in genes.  PloS One 7: e30158, 2012. View Abstract

Rebollo R, Farivar S & Mager DL. C-Gate – catalogue of genes affected by transposable elements. Mobile DNA 3: 9, 2012. View Abstract

Rebollo R, Zhang Y & Mager DL. Transposable elements: not as quiet as a mouse. Genome Biol 13:159, 2012. View Abstract

2011

Cohen CJ, Crome SQ, MacDonald KG, Dai EL, Mager DL & Levings MK. Human Th1 and Th17 cells exhibit epigenetic stability at signature cytokine and transcription factor loci.  J Immunol  187: 5615-5626, 2011. View Abstract

Rebollo R, Karimi MM, Bilenky M, Gagnier L, Miceli-Royer K, Zhang Y, Goyal P, Keane TM, Jones S, Hirst M, Lorincz MC & Mager DL.  Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms.  PLoS Genet 7: e1002301, 2011. View Abstract

Cohen CJ, Rebollo R, Babovic S, Dai EL, Robinson WP & Mager DL. Placenta-specific expression of the IL-2 receptor B subunit from an endogenous retroviral promoter.  J Biol Chem 286: 35543-35552, 2011.  View Abstract

Karimi MM, Goyal P, MaksakovaIA, Bilenky M, Leung D, Tang JX, Shinkai Y,Mager DL, Jones S, Hirst M & Lorincz MC. DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements and chimaeric transcripts in mESCs.  Cell Stem Cell 8: 676-687, 2011. View Abstract

Leung DC, Dong KB, Maksakova IA, Goyal P, Appanah R, Lee S, Tachibana M, Shinkai Y, Lehnertz B, Mager DL, Rossi F & Lorincz MC. Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing.  Proc Natl Acad Sci USA 108: 5718-5723, 2011. View Abstract

Maksakova IA, Goyal P, Bullwinkel J, Brown JP, Bilenky M, Mager DL, Singh PB & Lorincz MC. H3K9me3 binding proteins are dispensable for SETDB1/H3K9me3-dependent retroviral silencing.  Epigen Chromatin 4: 12, 2011. View Abstract

Plamondon JA, Harris MJ, Mager DL, Gagnier L & Juriloff DM. The clf2 gene has an epigenetic role in the multifactorial etiology of cleft lip and palate in the A/WySn mouse strain.  Birth Defects Res A Clin Mol Teratol  91: 716-727, 2011.  View Abstract

Zhang Y, Romanish MT & Mager DL. Distributions of transposable elements reveal hazardous zones in mammalian introns.  PLoS Comput Biol 7: 1-13, 2011. View Abstract    

2010

Argiropoulos B, Palmqvist L, Imren S, Miller M, Rouhi A, Mager DL & Humphries RK. Meis1 disrupts the genomic imprint of Dlk1 in a NUP98-HOXD13 leukemia model.  Leukemia 24: 1788-1791, 2010. View Abstract

Reiss D, Zhang Y, Rouhi A, Reuter M & Mager DL. Variable DNA methylation of transposable elements: the case study of mouse early transposons.  Epigenetics 5: 1-12, 2010. View Abstract

Rogers SL, Zhao Y, Jiang X, Eaves CJ, Mager DL & Rouhi A. Expression of the leukemic prognostic marker CD7 is linked to epigenetic modifications in chronic myeloid leukemia.  Mol Cancer 9: 41 2010. View Abstract

 

Romanish MT, Cohen CJ & Mager DL. Potential mechanisms of endogenous retroviral-mediated genomic instability in human cancer.  Semin Cancer Biol 20: 246-253, 2010. View Abstract

2009

Rouhi A, Lai CB, Cheng TP, Takei F, Yokoyama WM & Mager DL. Evidence for high bi-allelic expression of activating Ly49 receptors.  Nucleic Acids Res  37: 5331-5342, 2009. View Abstract

Cohen C, Lock W & Mager DL. Endogenous retroviral LTRs as promoters for human genes: a critical assessment.  Gene  448: 105-114, 2009. View Abstract

Hotta A, Cheung AYL, Farra N, Vijayaragavan K, Seguin CA, Draper JS, Pasceri P, Maksakova IA, Mager DL, Rossant J, Bhatia M & Ellis J. Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency.  Nat Methods 6: 370-376, 2009. View Abstract

Romanish MT, Nakamura H, Lai CB, Wang Y & Mager DL. A novel protein isoform of the multicopy human NAIP gene derives from intragenic Alu SINE promoters.  PLoS One 4: e5761, 2009.  View Abstract

Lai CB, Zhang Y, Rogers SL & Mager DL. Creation of the two isoforms of rodent NKG2D was driven by a B1 retrotransposon insertion.  Nucleic Acids Res  37: 3032-3043, 2009. View Abstract

MaksakovaIA, Zhang Y, van de Lagemaat LN & Mager DL. Preferential epigenetic suppression of the autonomous MusD over the non-autonomous ETn mouse retrotransposons.  Mol Cell Biol 29: 2456-2468, 2009.  View Abstract

2008

Dong KB, Maksakova IA, Mohn F, Leung D, Appanah R, Lee S, Yang HW, Lam LL, Mager DL, Schubeler D, Tachibana M, Shinkai Y & Lorincz MC. DNA methylation in ES cells requires the lysine methyltransferase G9a but not its catalytic activity.  EMBO J 27: 2691-2701, 2008. View Abstract

MaksakovaIA, Mager DL & Reiss D. Keeping active endogenous retroviral elements in check: the epigenetic perspective.  Cell Mol Life Sci 65 (Suppl. Endogenous Retroviruses): 3329-3347, 2008. View Abstract

Rouhi A, Mager DL, Humphries RK & Kuchenbauer F. MiRNAs, epigenetics and cancer.  Mamm Genome  19: 517-525, 2008.  View Abstract

Zhang Y, MaksakovaIA, Gagnier L, van de Lagemaat LN & Mager DL. Genome-wide assessments reveal extremely high levels of polymorphism of two active families of mouse endogenous retroviral elements.  PLoS Genet 4:e1000007, 2008. View Abstract

2007

Reiss D, Zhang Y, & Mager DL. Widely variable endogenous retroviral methylation levels in human placenta. Nucleic Acids Res 35 (14): 4743-54, 2007. View Abstract

Wilson EB, Parachoniak CA, Carpenito C, Mager DL, & Takei F. Expression of murine killer immunoglobulin-like receptor KIRL1 on CD1d-independent NK1.1(+) T cells. Immunogenetics 59 (8): 641-51, 2007. View Abstract

Romanish MT, Lock WM, van de Lagemaat LN, DunnCA, & Mager DL. Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution. PLoS Genet 3 (1): e10, 2007. View Abstract

Reiss D, & Mager DL. Stochastic epigenetic silencing of retrotransposons: does stability come with age? Gene 390 (1-2): 130-5, 2007. View Abstract

Rouhi A, Brooks CG, Takei F, & Mager DL. Plasticity of Ly49g expression is due to epigenetics. Mol Immunol 44 (5): 821-6, 2007. View Abstract

2006

van de Lagemaat LN, Medstrand P, & Mager DL. Multiple effects govern endogenous retrovirus survival patterns in human gene introns. Genome Biol 7 (9): R86, 2006. View Abstract

Gerlo S, Davis JR, Mager DL, & Kooijman R. Prolactin in man: a tale of two promoters. Bioessays 28 (10): 1051-5, 2006. View Abstract

Rogers SL, Rouhi A, Takei F, & Mager DL. A role for DNA hypomethylation and histone acetylation in maintaining allele-specific expression of mouse NKG2A in developing and mature NK cells. J Immunol 177 (1): 414-21, 2006. View Abstract

Rouhi A, Gagnier L, Takei F, & Mager DL. Evidence for epigenetic maintenance of Ly49a monoallelic gene expression. J Immunol 176 (5): 2991-9, 2006. View Abstract

Maksakova IA, Romanish MT, Gagnier L, Dunn CA, van de Lagemaat LN, & Mager DL. Retroviral elements and their hosts: insertional mutagenesis in the mouse germ line. PLoS Genet 2 (1): e2, 2006. View Abstract

DunnCA, RomanishMT, Gutierrez LE, van de Lagemaat LN, & Mager DL. Transcription of two human genes from a bidirectional endogenous retrovirus promoter. Gene 366 (2): 335-42, 2006. View Abstract

2005

MaksakovaIA, & Mager DL. Transcriptional regulation of early transposon elements, an active family of mouse long terminal repeat retrotransposons. J Virol 79 (22): 13865-74, 2005. View Abstract

van de Lagemaat LN, Gagnier L, Medstrand P, & Mager DL. Genomic deletions and precise removal of transposable elements mediated by short identical DNA segments in primates. Genome Res 15 (9): 1243-9, 2005. View Abstract

DunnCA, van de Lagemaat LN, Baillie GJ, & Mager DL. Endogenous retrovirus long terminal repeats as ready-to-use mobile promoters: the case of primate beta3GAL-T5. Gene 364: 2-12, 2005. View Abstract

Medstrand P, van de Lagemaat LN, Dunn CA, Landry JR, Svenback D, & Mager DL. Impact of transposable elements on the evolution of mammalian gene regulation. Cytogenet Genome Res 110 (1-4): 342-52, 2005. View Abstract

DunnCA, & Mager DL. Transcription of the human and rodent SPAM1 / PH-20 genes initiates within an ancient endogenous retrovirus. BMC Genomics 6 (1): 47, 2005. View Abstract

2004

Wilhelm BT, & Mager DL. Rapid expansion of the Ly49 gene cluster in rat. Genomics 84 (1): 218-21, 2004. View Abstract

Baillie GJ, van de Lagemaat LN, Baust C, & Mager DL. Multiple groups of endogenous betaretroviruses in mice, rats, and other mammals. J Virol 78 (11): 5784-98, 2004. View Abstract

2003

Mager DL & Medstrand P. Retroviral repeat sequences. In:  Nature Encyclopedia of the Human Genome., Vol. 5, Nature Publishing Group, pp 57-63, 2003.

Landry JR, Mager DL, & Wilhelm BT. Complex controls: the role of alternative promoters in mammalian genomes. Trends Genet 19 (11): 640-8, 2003. View Abstract

Baust C, Gagnier L, Baillie GJ, Harris MJ, Juriloff DM, & Mager DL. Structure and expression of mobile ETnII retroelements and their coding-competent MusD relatives in the mouse. J Virol 77 (21): 11448-58, 2003. View Abstract

van de Lagemaat LN, Landry JR, Mager DL, & Medstrand P. Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends Genet 19 (10): 530-6, 2003. View Abstract

DunnCA, Medstrand P, & Mager DL. An endogenous retroviral long terminal repeat is the dominant promoter for human beta1,3-galactosyltransferase 5 in the colon. Proc Natl Acad Sci U S A 100 (22): 12841-6, 2003. View Abstract

Wilhelm BT, Landry JR, Takei F, & Mager DL. Transcriptional control of murine CD94 gene: differential usage of dual promoters by lymphoid cell types. J Immunol 171 (8): 4219-26, 2003. View Abstract

Landry JR, & Mager DL. Functional analysis of the endogenous retroviral promoter of the human endothelin B receptor gene. J Virol 77 (13): 7459-66, 2003. View Abstract

Wilhelm BT, & Mager DL. Identification of a new murine lectin-like gene in close proximity to CD94. Immunogenetics 55 (1): 53-6, 2003. View Abstract

Gagnier L, Wilhelm BT, & Mager DL. Ly49 genes in non-rodent mammals. Immunogenetics 55 (2): 109-15, 2003. View Abstract

Wilhelm BT, Gagnier L, & Mager DL. Sequence analysis of the ly49 cluster in C57BL/6 mice: a rapidly evolving multigene family in the immune system. Genomics 80 (6): 646-61, 2002. View Abstract

2002

Landry JR, Rouhi A, Medstrand P, & Mager DL. The Opitz syndrome gene Mid1 is transcribed from a human endogenous retroviral promoter. Mol Biol Evol 19 (11): 1934-42, 2002. View Abstract

Landry JR, & Mager DL. Widely spaced alternative promoters, conserved between human and rodent, control expression of the Opitz syndrome gene MID1. Genomics 80 (5): 499-508, 2002. View Abstract

Medstrand P, van de Lagemaat LN, & Mager DL. Retroelement distributions in the human genome: variations associated with age and proximity to genes. Genome Res 12 (10): 1483-95, 2002. View Abstract

Baust C, Baillie GJ, & Mager DL. Insertional polymorphisms of ETn retrotransposons include a disruption of the wiz gene in C57BL/6 mice. Mamm Genome 13 (8): 423-8, 2002. View Abstract

McQueen KL, Wilhelm BT, Harden KD, & Mager DL. Evolution of NK receptors: a single Ly49 and multiple KIR genes in the cow. Eur J Immunol 32 (3): 810-7, 2002. View Abstract

2001

Landry JR, Medstrand P, & Mager DL. Repetitive elements in the 5’ untranslated region of a human zinc-finger gene modulate transcription and translation efficiency. Genomics 76 (1-3): 110-6, 2001. View Abstract

Takei F, McQueen KL, Maeda M, Wilhelm BT, Lohwasser S, Lian RH, & Mager DL. Ly49 and CD94/NKG2: developmentally regulated expression and evolution. Immunol Rev 181: 90-103, 2001. View Abstract

Wilhelm BT, McQueen KL, Freeman JD, Takei F, & Mager DL. Comparative analysis of the promoter regions and transcriptional start sites of mouse Ly49 genes. Immunogenetics 53 (3): 215-24, 2001. View Abstract

Mager DL, McQueen KL, Wee V, & Freeman JD. Evolution of natural killer cell receptors: coexistence of functional Ly49 and KIR genes in baboons. Curr Biol 11 (8): 626-30, 2001. View Abstract

McQueen KL, Wilhelm BT, Takei F, & Mager DL. Functional analysis of 5’ and 3’ regions of the closely related Ly49c and j genes. Immunogenetics 52 (3-4): 212-23, 2001. View Abstract

Medstrand P, Landry JR, & Mager DL. Long terminal repeats are used as alternative promoters for the endothelin B receptor and apolipoprotein C-I genes in humans. J Biol Chem 276 (3): 1896-903, 2001. View Abstract

2000

Mager DL, & Freeman JD. Novel mouse type D endogenous proviruses and ETn elements share long terminal repeat and internal sequences. J Virol 74 (16): 7221-9, 2000. View Abstract

1999

Mager DL, Hunter DG, Schertzer M, & Freeman JD. Endogenous retroviruses provide the primary polyadenylation signal for two new human genes (HHLA2 and HHLA3). Genomics 59 (3): 255-63, 1999. View Abstract

McQueen KL, Lohwasser S, Takei F, & Mager DL. Expression analysis of new Ly49 genes: most transcripts of Ly49j lack the transmembrane domain. Immunogenetics 49 (7-8): 685-91, 1999. View Abstract

KowalskiPE, Freeman JD, & Mager DL. Intergenic splicing between a HERV-H endogenous retrovirus and two adjacent human genes. Genomics 57 (3): 371-9, 1999. View Abstract

1998

Medstrand P, & Mager DL. Human-specific integrations of the HERV-K endogenous retrovirus family. J Virol 72 (12): 9782-7, 1998. View Abstract

McQueen KL, Freeman JD, Takei F, & Mager DL. Localization of five new Ly49 genes, including three closely related to Ly49c. Immunogenetics 48 (3): 174-83, 1998. View Abstract

KowalskiPE, & Mager DL. A human endogenous retrovirus suppresses translation of an associated fusion transcript, PLA2L. J Virol 72 (7): 6164-8, 1998. View Abstract

1997

Takei F, Brennan J, & Mager DL. The Ly-49 family: genes, proteins and recognition of class I MHC. Immunol Rev 155: 67-77, 1997. View Abstract

1996

Brennan J, Lemieux S, Freeman JD, Mager DL, & Takei F. Heterogeneity among Ly-49C natural killer (NK) cells: characterization of highly related receptors with differing functions and expression patterns. J Exp Med 184 (6): 2085-90, 1996. View Abstract

Mager Lab Sept 2015

Vancouver, BC --  26 November 2013 -- Artem Babaian (Photo: BC Cancer Agency)

Artem Babaian

Graduate Student
Vancouver, BC --  26 November 2013 -- Liane Gagner (Photo: BC Cancer Agency)

Liane Gagnier

Natasha

Natasha Little

Graduate Student
Vancouver, BC --  26 November 2013 -- Frances Locke  (Photo: BC Cancer Agency)

Dr Frances Lock

PhD
Postdoctoral Fellow
Samantha1

Samantha Schaffner

NSERC Summer Student