Program Leader, Genetic Mechanisms of Cancer Research Program
Associate Professor, Department of Genetics, Cell Biology and Development

larga002@umn.edu
612-626-4979 — office
612-626-6971 — lab
Preferred method of contact: e-mail

Dr. Largaespada received his Ph.D. in Cellular and Molecular Biology at the University of Wisconsin-Madison in 1992. He joined the University of Minnesota's Department of Laboratory Medicine and Pathology in 1996 and the Department of Genetics, Cell Biology and Development in 1999, where he is currently an Associate Professor. He holds the Margaret Harvey Schering Chair in Cancer Genetics.

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 solid tumors such as sarcoma, prostate, colorectal and lung cancer.

Selected Publications

Wiesner SM, Johnson JM, Hasz DE, Largaespada DA. A repressible transgenic model of NRAS oncogene driven mast cell disease in the mouse. Blood 2005;106:1054-1062.

Collier LS, Carlson CM, Ravimohan S, Dupuy AJ, Largaespada DA. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature 2005;436:272-276.

Dupuy AJ, Akagi K, Largaespada DA, Copeland NG, and Jenkins NA. Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system. Nature 2005;436:221-226.

Starr TK, Largaespada DA. Cancer gene discovery using the Sleeping Beauty transposon. Cell Cycle. 2005;4:1744-1748.

Ohlfest JR, Demorest ZL, Motooka Y, Vengco I, Oh S, Chen E, Scappaticci FA, Saplis RJ, Ekker SC, Low WC, Freese AB, Largaespada DA. 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. 2005;12:778-88.

Carlson CM, Frandsen JL, Kirchhof N, McIvor RS, Largaespada DA. Somatic integration of an oncogene-harboring Sleeping Beauty transposon models liver tumor development in the mouse. Proc Natl Acad Sci USA 2005;102:17059-17064.

Collier LS, Largaespada DA. Transforming science: cancer gene identification. Curr Opin Genet Dev. 2006;16:23-29.

Yin B, Morgan K, Hasz DE, Mao Z, Largaespada DA. Nf1 gene inactivation in acute myeloid leukemia cells confers cytarabine resistance through MAPK and mTOR pathways. Leukemia 2006;20:151-154.

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, Largaespada DA. Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers. PloS Genetics 2006;2:e156.

Kim A*, Morgan K*, Hasz DE, Wiesner SM, Lauchle JO, Geurts JL, Diers MD, Doan TL, Kogan SK, Parada LF, Shannon K, Largaespada DA. b-Common receptor inactivation attenuates myeloproliferative disease in Nf1 mutant mice. Blood 2007;109:1687-1691. *Equal contribution 

Morgan KJ, Rowley MA, Wiesner SM, Hasz DE, Van Ness B, Largaespada DA. The GAP-related domain of neurofibromin attenuates proliferation and downregulates N- and K-Ras activation in Nf1-negative AML cells. Leuk Res. 2007;31:1115-1121.

Yin B, Tsai ML, Hasz DE, Rathe SK, Le Beau MM, Largaespada DA.A microarray study of altered gene expression after cytarabine resistance in acute myeloid leukemia. Leukemia. 2007;21:1093-1097.

Kim WI, Wiesner SM, Largaespada DA.Vav promoter-tTA conditional transgene expression system for hematopoietic cells drives high level expression in developing B and T cells. Exp Hematol. 2007;35:1231-1239.

Collier LS and Largaespada DA. Transposons for cancer gene discovery: Sleeping Beauty and beyond. Genome Biol. 2007;8 Suppl 1:S5.

Collier LS and Largaespada DA. Transposable elements and the dynamic somatic genome. Genome Biol. 2007;8 Suppl 1:S5.

Wangensteen KJ, Wilber A, Keng VW, Chen Y, Matise I, Wangensteen L, Steer CJ, McIvor RS, Largaespada DA, Wang X, Ekker SC. A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver. Hepatology, in press.