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

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 a professor. He holds the Margaret Harvey Schering Chair in Cancer Genetics.

Research Interests

cancer genetics, insertional mutagenesis, transposons, Sleeping Beauty, murine leukemia viruses, brain tumors, sarcoma, myeloid leukemia, colorectal cancer, hepatocellular carcinoma, neurofibromatosis type 1

Techniques:

Mouse transgenesis, next generation sequencing, tissue culture, in vivo imaging, molecular biology

Dr. Largaespada's laboratory is working to exploit insertional mutagenesis for cancer gene discovery and functional genomics in the mouse. The Largaespada lab is using a vertebrate-active transposon system, called Sleeping Beauty (SB), for insertional mutagenesis in mouse somatic and germline cells, and for gene therapy. Using SB they have developed a powerful method to find new cancer genes using transgenic mouse models. This approach can be used to understand the genetic basis of many types of cancer, including brain tumors, carcinomas of the liver and gastrointestinal tract, leukemias, sarcomas, and many more (Collier, Carslon et al., Nature, 2005; Dupuy et al., Nature, 2005, Keng et al., Nature Biotechnology, 2009; Starr et al., Science, 2009). Insertional mutagenesis is also being used to identify genes and genetic pathways underlying acute myeloid leukemia (AML) development. Ongoing work includes genetic studies of myeloid leukemia chemotherapy resistance and RAS pathway oncogene addiction.

For more information about Dr. Largaespada's research interests, visit the Center for Genome Engineering Web site.

Selected Publications

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. Nat Genet. 1999;23:348-353

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. 2002;99:4495-4499.

Carlson C, Dupuy A, Fritz S, Roberg-Perez K, Fletcher CF, Largaespada DA. Transposon mutagenesis of the mouse germline. Genetics 2003;165:243-256.

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 2005; 436:272-276.

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

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.

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 Genet. 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. 109:1687-91. (2007) *Equal contribution.

Yin B, Delwel R, Valk PJ, Wallace MR, Loh ML, Shannon KM, Largaespada DA. A retroviral mutagenesis screen reveals strong cooperation between Bcl11a overexpression and loss of the Nf1 tumor suppressor gene.  Blood 2009;113:1075-1085.

Kim, WI, Matise I, Diers MD, Largaespada DA. Ras oncogene suppression induces apoptosis followed by more differentiated less myelosuppressive disease upon relapse of acute myeloid leukemia. Blood 2009;113:1086-1096.

Wiesner SM, Decker SA, Larson JD, Ericson K, Forster C, Gallardo JL, Long C, Demorest ZL, Zamora EA, Low WC, SantaCruz K, Largaespada DA, Ohlfest JR. De novo induction of genetically engineered brain tumors in mice using plasmid DNA. Cancer Res. 2009;69:431-439.

Keng VW, Villanueva A, Chiang DY, Dupuy, Ryan BJ1,2, Ilze Matise I1, Kevin A.T. Silverstein KAT, Sarver A, Starr TK, Akagi K, Tessarollo L, Collier LS, Powers S, Lowe SW, Jenkins NA, Copeland NG, Josep M. Llovet JM, Largaespada DA. A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma. Nature Biotech. 2009;27:264-274.

Starr TK, Allaei R, Silverstein KAT, Staggs RA, Sarver A, Bergemann TL, Gupta M, O'Sullivan MG, Matise I, Dupuy AJ, Collier LS, Powers S, Oberg AL, Asmann YW, Thibodeau SN, Tessarollo L, Copeland NG, Jenkins NA, Cormier RT, Largaespada DA. A transposon-based genetic screen in mice identifies genes altered in colorectal cancer. Science 2009;323:1747-1750.