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David Largaespada, Ph.D.

Professor

Mailing Address:
University of Minnesota
Department of Genetics, Cell Biology, and Development
6-160 Jackson
321 Church St. SE
Minneapolis, MN 55455
USA
Office:
5-104 MCB
P:612-626-4979

Email:
larga002@umn.edu

 Lab:
5-220 MCB
P:612-626-6971

Areas of Research Strength:

Mammalian Genetics
Genetic Mechanisms
Genomics

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Research Techniques:

Genomic cloning
Cell culture
Ras activation
Mouse transgenesi

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Research Interests:

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

Dr. Largaespada's laboratory is working to exploit insertional mutagenesis
for cancer gene discovery and functional genomics in the mouse. Mouse
models of murine leukemia virus induced acute myeloid leukemia (AML)
are being used to identify and characterize genes that have a role in
leukemia progression after disease is initiated by mutations relevant
to human AML. Ongoing work also includes genetic studies of myeloid
leukemia chemotherapy resistance and relapse. The Largaespada lab
has heavily invested in the use of a vertebrate-active transposon system,
called Sleeping Beauty, for insertional mutagenesis in mouse somatic
and germline cells and for gene therapy. SB is being used as a tool for
forward genetic screens for cancer genes involved in solid tumors such
as sarcoma, prostate and lung cancer.

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Selected Publications:

Thielen JL, Volzing KG, Collier LS, Green LE, Largaespada DA, and Marker PC.  Markers of prostate region-specific epithelial identity define anatomical locations in the mouse prostate that are molecularly similar to human prostate cancers.  Differentiation. 75:49-61. (2007).

Yin B*, Tsai ML*, Hasz DE, Rathe SK, Le Beau MM, and Largaespada DA.  A microarray study of altered gene expression after cytarabine resistance in acute myeloid leukemia.  Leukemia. In Press. *Equal contribution.

Kim A*, Morgan K*, Hasz DE, Wiesner SM, Lauchle JO, Geurts JL, Diers MD, Doan TL, Kogan SK, Parada LF, Shannon K, and Largaespada DA. -Common receptor inactivation attenuates myeloproliferative disease in Nf1 mutant mice. Blood. 109:1687-91. (2007) *Equal contribution.

Morgan K, Rowley MA, Wiesner SM, Hasz DE, Van Ness B, and Largaespada DA. The GAP-related domain of neurofibromin attenuates proliferation and downregulates N- and K-Ras activation in Nf1-negative AML cells. Leukemia Res. In Press.

Balciunas D, Wangensteen KJ, Wilber A, Bell J, Geurts A, Sivasubbu S, Wang X, Hackett PB, Largaespada DA, McIvor RS, Ekker SC.  Harnessing a High Cargo-Capacity Transposon for Genetic Applications in Vertebrates.  PLoS Genetics. Nov 10;2(11) 2006.

Geurts AM, Collier LS, Geurts JL, Leann L. Oseth LL, Bell ML, Mu D, Lucito R, Godbout SA, Green LE,  Lowe SW,  Hirsch BA,  Leinwand LA, and Largaespada DA. Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers. PloS Genetics. 2:e156 (2006).

Geurts AM, Wilber A, Carlson CM, Lobitz PD, Clarck KJ, Hackett PB, McIvor RS, and Largaespada DA. Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon.  BMC Biotech. 6:30 (2006).

Geurts AM, Hackett C, Bell J, Bergemann T, Collier LS, Carlson CM, Largaespada DA, and Hackett PH. Prediction of insertion-site preferences of mobile elements in chromosomes. Nuc. Acids Res. 34:2803-11. (2006).

Yin B, and Largaespada DA. Models of acute myeloid leukemia: Prospects for drug development and testing. Drug Discovery Today: Disease Models.  In Press.

Yin B, Kogan SC, Dickins RA, Lowe SW, and Largaespada DA.  Trp53 loss during in vitro selection contributes to acquired Ara-C resistance in acute myeloid leukemia.  Exp Hematology. 34:631-41. (2006).

Score PR, Belur LR, Frandsen JL, Guerts JL, Yamaguchi T, Somia NV, Hackett PB, Largaespada DA, and McIvor RS.Sleeping Beauty-Mediated Transposition and Long-Term Expression in Vivo: Use of the LoxP/Cre Recombinase System to Distinguish Transposition-Specific Expression. Mol Ther. 13:617-24. (2006).

Wilber A, Frandsen JL, Geurts JL, Largaespada DA, Hackett PB, and McIvor RS. RNA as a Source of Transposase for Sleeping Beauty-Mediated Gene Insertion and Expression in Somatic Cells and Tissues. Mol Ther. 13:625-30. (2006).

Collier LS, and Largaespada DA. Transforming science: cancer gene identification. Curr Opin Genet Dev. 16:23-9. (2006).

Yin B, Morgan K, Hasz DE, Mao Z, and Largaespada DA. Nf1 gene inactivation in acute myeloid leukemia cells confers cytarabine resistance through MAPK and mTOR pathways. . Leukemia. 20:151-4. (2006).

Carlson CM, Frandsen JL, Kirchhof N, McIvor RS, and Largaespada DA. 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. (2005).

Dupuy AJ, Akagi K, Largaespada DA, Copeland NG, and Jenkins NA. Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system. Nature. 436:221-6. (2005).

Collier LS, Carlson CM, Ravimohan S, Dupuy AJ and Largaespada DA. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature. 436:272-6. (2005).

Wiesner SM, Johnson JM, Hasz DE, and Largaespada DA. A repressible transgenic model of NRAS oncogene driven mast cell disease in the mouse. Blood. 106:1054-62. (2005).

Carlson C, Dupuy A, Fritz S, Roberg-Perez K, Fletcher CF, Largaespada DA. Transposon mutagenesis of the mouse germline. Genetics 165:243-56, (2003).

Dupuy A, Clark C, Carlson C, Fritz S, Davidson AE, Markley K, Finley K, Fletcher CF, Ekker S, Hackett P, Horn S, Largaespada DA. Mammalian germline transgenesis by transposition. Proc Natl Acad Sci 99:4495-9, (2002).

Dupuy A, Fritz S, Largaespada DA.  Transposition and gene disruption using a mutagenic transposon vector in the male germline of the mouse.  Genesis 30:82-8, (2001).

Li J, Shen H, Himmel KL, Dupuy AJ, Largaespada DA, Nakamura T, Shaughnessy Jr JD, Jenkins NA, Copeland NG. Leukemia disease genes: large scale cloning and pathway predictions. Nature Genetics 23:348-53, (1999).



To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed
search menu should say PubMed
type Largaespada DA in the avaliable line

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 Last modified on Wednesday, June 11, 2008