David A. Largaespada, Ph.D.

All Faculty	\|	Microbiology	\|	Immunology	\|	Cancer Biology	\|	Committee on Graduate Studies

David A. Largaespada, Ph.D.

Associate Professor

Department of Genetics, Cell Biology and Development

University of Wisconsin, Madison, 1992, Ph.D.

larga002@umn.edu

612-626-4979 office
612-626-6971 lab

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 (SB), 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 tumors of the gastrointestinal tract, prostate, lung and lymphoid tissues.

Selected Recent Publications:

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. 2007. b-Common receptor inactivation attenuates myeloproliferative disease in Nf1 mutant mice. Blood.109:1687-91. *Equal contribution.
Balciunas D, Wangensteen KJ, Wilber A, Bell J, Geurts A, Sivasubbu S, Wang X, Hackett PB, Largaespada DA, McIvor RS, Ekker SC. 2006. Harnessing a High Cargo-Capacity Transposon for Genetic Applications in Vertebrates. PLoS Genetics. Nov 10;2(11).
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. 2006. Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers. PLoS Genetics. 2:e156.
Geurts AM,Wilber A,Carlson CM, Lobitz PD, Clarck KJ, Hackett PB, McIvor RS, and Largaespada DA. 2006. Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon. BMC Biotech. 6:30.
Yin B, Kogan SC, Dickins RA, Lowe SW, and Largaespada DA. 2006. Trp53 loss during in vitro selection contributes to acquired Ara-C resistance in acute myeloid leukemia. Exp Hematology. 34:631-41.
Collier LS, and Largaespada DA. 2006. Transforming science: cancer gene identification. Curr Opin Genet Dev. 16:23-9.
Yin B, Morgan K, Hasz DE, Mao Z, and Largaespada DA. 2006. Nf1 gene inactivation in acute myeloid leukemia cells confers cytarabine resistance through MAPK and mTOR pathways. Leukemia.20:151-4.
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.
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.
Carlson C, Dupuy A, Fritz S, Roberg-Perez K, Fletcher CF, Largaespada DA. 2003. Transposon mutagenesis of the mouse germline. Genetics 165:243-56.
Dupuy A, Clark C, Carlson C, Fritz S, Davidson AE, Markley K, Finley K, Fletcher CF, Ekker S, Hackett P, Horn S, Largaespada DA. 2002. Mammalian germline transgenesis by transposition. Proc Natl Acad Sci99:4495-9.
Dupuy A, Fritz S, Largaespada DA. 2001. Transposition and gene disruption using a mutagenic transposon vector in the male germline of the mouse. Genesis 30:82-8.
Li J, Shen H, Himmel KL, Dupuy AJ, Largaespada DA, Nakamura T, Shaughnessy Jr JD, Jenkins NA, Copeland NG. 1999. Leukemia disease genes: large scale cloning and pathway predictions. Nature Genetics 23:348-53.

Last modified on: April 5, 2007