Contact IMV

IMV Executive Assistant

email: virology@umn.edu

tel. (612) 624-1926

fax. (612) 625-1108

 

18-242 Moos Tower
515 Delaware St. SE
Minneapolis, MN 55455

General Questions:

virology@umn.edu

David Largaespada,
Professor, Margaret Harvey Schering Land Grant Chair in Cancer Genetics, Associate Director, Basic Sciences, Masonic Cancer Center

 

Masonic Cancer Center, Medical School

Phone: 612-626-4979

Email: larga002@umn.edu

Research Interests

cancer genetics, myeloid leukemia, Neurofibromatosis type 1 (Nf1) gene, signal transduction, insertional mutagenesis, murine leukemia virus, transposons

Dr. Largaespada's laboratory is working to exploit insertional mutagenesis for cancer gene discovery. A mouse model of murine leukemia virus induced acute myeloid leukemia is being used to identify and characterize genes that have a role in myeloid leukemia development. Dr. Largaespada is focusing on genes that cooperate with known human leukemia gene mutations, including loss of the Neurofibromatosis type 1 gene and expression of the AML1/ETO fusion gene. Ongoing work also includes genetic studies of myeloid leukemia chemoresistance and relapse using mouse models. In addition, the Largaespada lab is adapting a recently constructed transposon system, called Sleeping Beauty, for insertional mutagenesis in mouse somatic and germline cells and for gene therapy.

Selected Recent Publications

  • Geurts A.M., Collier L.S., Geurts J.L., Leann L. Oseth L.L.,  Bell M.L.,  Mu D, Lucito R, Godbout S.A., Green L.E.,  Lowe S.W.,  Hirsch B.A.,  Leinwand L.A., and Largaespada D.A. Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers. PloS Genetics.  In Press
  • Geurts A.M.,Wilber A.,Carlson C.M., Lobitz P.D., Clarck K.J., Hackett P.B., McIvor R.S., and Largaespada, D.A. Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon.  BMC Biotech In Press .
  • Yin B., Scott C., Kogan S.C., and Largaespada D.A.  2006. Trp53 loss during in vitro selection contributes to acquired Ara-C resistance in acute myeloid leukemia.  Exp Hematology. 34:631-41.
  • Yin B., Morgan K., Hasz D.E., Mao Z., and Largaespada D.A. 2006. Nf1 gene inactivation in acute myeloid leukemia cells confers cytarabine resistance through MAPK and mTOR pathways. Leukemia.20:151-4.
  • Collier L.S., and Largaespada D.A. 2006. Transforming science: cancer gene identification. Curr Opin Genet Dev. 16:23-9.
  • Carlson C.M., Frandsen J.L., Kirchhof N., McIvor R.S., and Largaespada D.A. 2005. Somatic integration of an oncogene-harboring Sleeping Beauty transposon models liver tumor development in the mouse. Proc Natl Acad Sci U S A. 102:17059-64.
  • Ohlfest J.R., Demorest Z.L., Motooka Y., Vengco I., Oh S., Chen E., Scappaticci F.A., Saplis R.J., Ekker S.C., Low W.C., Freese A.B., and Largaespada D.A. 2005. Combinatorial antiangiogenic gene therapy by nonviral gene transfer using the Sleeping Beauty transposon causes tumor regression and improves survival in mice bearing intracranial human glioblastoma.  Mol. Ther . 12:778-88.
  • Carlson C.M. and Largaespada D.A.  2005. Insertional mutagenesis in mice: New perspectives and tools.  Nature Reviews Genetics , 6:568-80.
  • Dupuy A.J., Akagi K., Largaespada D.A., Copeland N.G., and Jenkins N.A. 2005. Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system. Nature . 436:221-6.
  • Collier L.S., Carlson C.M, Ravimohan S., Dupuy A.J. and Largaespada D.A.  2005. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature . 436:272-6.
  • Bell ML, Mu D, Lucito R, Godbout SA, Green LE, Lowe SW, Hirsch BA, Leinwand LA, Largaespada DA. 2006. Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers. PLoS Genet. 2(9):e156. Epub 2006 Aug 3.
  • Geurts AM, Wilber A, Carlson CM, Lobitz PD, Clark KJ, Hackett PB, McIvor RS, Largaespada DA. 2006. Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon. BMC Biotechnol. 6:30.
  • Geurts AM, Hackett CS, Bell JB, Bergemann TL, Collier LS, Carlson CM, Largaespada DA, Hackett PB. 2006. Structure-based prediction of insertion-site preferences of transposons into chromosomes. Nucleic Acids Res. 34(9):2803-11. Print 2006.
  • Yin B, Kogan SC, Dickins RA, Lowe SW, Largaespada DA. 2006. Trp53 loss during in vitro selection contributes to acquired Ara-C resistance in acute myeloid leukemia. Exp Hematol. 34(5):631-41.
  • Wilber A, Frandsen JL, Geurts JL, Largaespada DA, Hackett PB, McIvor RS. 2006. RNA as a source of transposase for sleeping beauty-mediated gene insertion and expression in somatic cells and tissues. Mol Ther. 13(3):625-30. Epub 2005 Dec 20 .
  • Score PR, Belur LR, Frandsen JL, Guerts JL, Yamaguchi T, Somia NV, Hackett PB, Largaespada DA, McIvor RS. 2006. Sleeping Beauty-mediated transposition and long-term expression in vivo: use of the LoxP/Cre recombinase system to distinguish transposition-specific expression. Mol Ther. 13(3):617-24.
  • Collier LS, and Largaespada DA. 2006. Transforming science: cancer gene identification. Curr Opin Genet Dev. 16:23-9.
  • Carlson CM, Frandsen JL, Kirchhof N, McIvor RS, and Largaespada DA. 2005. Somatic integration of an oncogene-harboring Sleeping Beauty transposon models liver tumor development in the mouse. Proc Natl Acad Sci U S A. 102:17059-64.
  • Ohlfest JR, Demorest ZL, Motooka Y, Vengco I, Oh S, Chen E, Scappaticci FA, Saplis RJ, Ekker SC, Low WC, Freese AB, and Largaespada DA. 2005. Combinatorial antiangiogenic gene therapy by nonviral gene transfer using the Sleeping Beauty transposon causes tumor regression and improves survival in mice bearing intracranial human glioblastoma. Mol. Ther. 12:778-88.
  • Dupuy AJ, Akagi K, Largaespada DA, Copeland NG, and Jenkins NA. 2005. Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system. Nature. 436:221-6.
  • Collier LS, Carlson CM, Ravimohan S, Dupuy AJ and Largaespada DA. 2005. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature. 436:272-6.
  • Wiesner SM, Johnson JM, Hasz DE, and Largaespada DA. 2005. A repressible transgenic model of NRAS oncogene driven mast cell disease in the mouse. Blood. 106:1054-62.
  • Ohlfest JR, Lobitz P, Perkinson S, Largaespada DA. 2004. Integration and long-term expression in xenografted human glioblastoma cells using plasmid-based transposon system. Mol. Ther.
  • Belur LR, Frandsen J, Dupuy A, Largaespada DA, Hackett P, and McIvor RS. 2003. Gene insertion and long-term expression in lung mediated by the Sleeping Beauty transposon system. Mol Ther. 8:501-7.
  • Geurts AM, Yang Y, Clark KJ, Liu G, Cui Z, Dupuy AJ, Largaespada DA, and Hackett PB. 2003. Gene Transfer into Genomes of Human Cells by the Sleeping Beauty Transposon System. Mol Ther 8:108-117.
  • Carlson C, Dupuy A, Fritz S, Roberg-Perez K, Fletcher CF, Largaespada DA. 2003. Transposon mutagenesis of the mouse germline. Genetics. 165:243-256 .
  • Roberg-Perez, K, Carlson, C., and Largaespada, D. A. 2003. MTID: a database of Sleeping Beauty transposon insertions in mice. Nuc. Acids. Res. 31:78-81.
  • Largaespada, DA. 2003. Genetically modified mice in cancer research. Methods Mol Biol. 209:311-32.
  • Rizvi, T.A., Huang, Y., Sidani, A., Atit, R., Largaespada, D.A., Boissy, R.E., and Ratner N. 2002. A novel cytokine pathway suppresses glial cell melanogenesis after injury to adult nerve. J. Neurosci. 22:9831-40.
  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. 2002. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 418: 41-9.
  • Dupuy, A., Clark, C., Carlson, C., Fritz, S., Finley, K., Ekker, S., Hackett, P., Horn, S. and Largaespada, D. A. Mammalian Germline Transgenesis by Transposition. Proc. Natl. Acad. Sci., 99: 4495-4499..
  • Himmel, K. L., Bi, F., Shen, H., Copeland, N. G., Jenkins, N. A., Zheng, Y., and. Largaespada, D. A. 2002. Activation of a Novel Cdc42-Specific Guanine Nucleotide Exchange Factor by Proviral Insertion at Evi24, a Common Integration Site in B Cell and Myeloid Leukemia. J. Biol. Chem., 277: 13463-13472.
  • Largaespada, D. A. 2001. Haploinsufficiency for tumor suppression: The Hazards of being single and living a long time. J. Exp. Med. 193: F15-18.
  • Dupuy, A. J., Morgan, K., Von Lintig, F. C., Shen, H., Acar, H., Hasz, D. E., Jenkins, N. A., Copeland, N. G., Boss, G., and Largaespada, D. A. 2001. Activation of the Rap1 guanine nucleotide exchange gene, Cdg1, in BXH2 murine myeloid leukemia. J. Biol. Chem. 276: 11804-11811.
  • Dupuy, A., Fritz, S., and Largaespada, D. A. 2001. Transposition and Gene Disruption using a Mutagenic Transposon Vector in the Male Germline of the Mouse. Genesis, 30: 82-88.

Featured News & Events

'Wisc-e-sota', a Joint UMN-UW Virology Training Grant Symposium was first held on Friday, Sepbember 20th, 2013 at the Uniiversity of Wisconsin-La Crosse, Cartwright Center. This was the inaugural collaborative symposium of the NIH T32-supported virology training programs at the University of Wisconsin-Madison and the University of Minnesota-Twin Cities. Talks and poster sessions were presented by students, postdocs and faculty. The second UMN-UW Virology Training Grant Symposium will be held in the Fall 2014. Details to follow.

The 2014 IMV Symposium will be held on May 12, 2014 and Mark Denison (Vanderbilt) and Bert Semler (UC-Irvine) will be the Keynote Speakers. Click on the link below to register and submit abstracts.

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