David A. Largaespada, PhD

Professor, Department of Pediatrics

David A. Largaespada

Contact Info

Office Phone 612-626-4979

Fax 612-625-9810

Lab Phone 612-626-6971

Office Address:
Cancer and Cardiovascular Research Building
2231 6th St SE
Office 3-129
Minneapolis, MN 55455

Mailing Address:
Masonic Cancer Research Ctr
1st Floor Mailroom CCRB
2812A
2231 6th St SE
Minneapolis, MN 55455

Administrative Assistant Name
Rebecca Godar

Administrative Phone
612-624-0369

Professor, Department of Pediatrics

Professor, Department of Cell Biology and Development Genetics

Director for Basic Research, Masonic Cancer Center (MCC)

Director, Brain Tumor Program, Masonic Cancer Center (MCC)

Advising Faculty of Molecular, Cellular, Developmental Biology & Genetics (MCDB&G), Department of Cell Biology and Development Genetics

Advising Faculty, Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program


PhD, University of Wisconsin-Madison (Cellular and Molecular Biology), 1992

Summary

Dr. Largaespada received his PhD 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 Hedberg Family/Children's Cancer Research Fund Chair in Brain Tumor Research.

Awards & Recognition

  • Hedberg Family/Children's Cancer Research Fund Chair in Brain Tumor Research

Research

Research Summary/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.

Research Methods/Techniques

Genomic cloning, Cell culture, Ras activation, Mouse transgenesis

Publications

For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.

  • Keng VW, Sia D, Sarver AL, Tschida BR, Fan D, Alsinet C, Solé M, Lee WL, Kuka TP, Moriarity BS, Villanueva A, Dupuy AJ, Riordan JD, Bell JB, Silverstein KA, Llovet JM, Largaespada DA. Gender bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR. Hepatology. 2012 Aug 16. doi: 10.1002/hep.26004. PMID:22899566
  • Keng VW, Largaespada DA, Villanueva A. Why men are at higher risk for hepatocellular carcinoma? J Hepatol. 2012 Aug;57(2):453-4. PMID: 22425699
  • Keng VW, Rahrmann EP, Watson AL, Tschida BR, Moertel CL, Jessen WJ, Rizvi TA, Collins MH, Ratner N, Largaespada DA. PTEN and NF1 Inactivation in Schwann Cells Produces a Severe Phenotype in the Peripheral Nervous System That Promotes the Development and Malignant Progression of Peripheral Nerve Sheath Tumors. Cancer Res. 2012 Jun 14 PMID:22700876
  • Bergemann TL, Starr TK, Yu H, Steinbach M, Erdmann J, Chen Y, Cormier RT, Largaespada DA, Silverstein KA. New methods for finding common insertion sites and co-occurring common insertion sites in transposon- and virus-based genetic screens. Nucleic Acids Res. 2012 May;40(9):3822-33. PMID: 22241771
  • Bergerson RJ, Collier LS, Sarver AL, Been RA, Lugthart S, Diers MD, Zuber J, Rappaport AR, Nixon MJ, Silverstein KA, Fan D, Lamblin AF, Wolff L, Kersey JH, Delwel R, Lowe SW, O'Sullivan MG, Kogan SC, Adams DJ, Largaespada DA. An insertional mutagenesis screen identifies genes that cooperate with Mll-AF9 in a murine leukemogenesis model. Blood. 2012 May 10;119(19):4512-23. PMID:
  • 22427200
  • Pérez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A, Sarver AL, Silverstein KA, Grützmann R, Aust D, Rümmele P, Knösel T, Herd C, Stemple DL, Kettleborough R, Brosnan JA, Li A, Morgan R, Knight S, Yu J, Stegeman S, Collier LS, ten Hoeve JJ, de Ridder J, Klein AP, Goggins M, Hruban RH, Chang DK, Biankin AV, Grimmond SM; Australian Pancreatic Cancer Genome Initiative, Wessels LF, Wood SA, Iacobuzio-Donahue CA, Pilarsky C, Largaespada DA, Adams DJ, Tuveson DA. The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature. 2012 Apr 29;486(7402):266-70. doi:
  • 10.1038/nature11114. PMID:22699621
  • Seshagiri S, Stawiski EW, Durinck S, Modrusan Z, Storm EE, Conboy CB, Chaudhuri S, Guan Y, Janakiraman V, Jaiswal BS, Guillory J, Ha C, Dijkgraaf GJ, Stinson J, Gnad F, Huntley MA, Degenhardt JD, Haverty PM, Bourgon R, Wang W, Koeppen H, Gentleman R, Starr TK, Zhang Z, Largaespada DA, Wu TD, de Sauvage FJ. Recurrent R-spondin fusions in colon cancer. Nature. 2012 Aug 15. doi: 10.1038/nature11282. PMID: 22895193
  • Wu X, Northcott PA, Dubuc A, Dupuy AJ, Shih DJ, Witt H, Croul S, Bouffet E, Fults DW, Eberhart CG, Garzia L, Van Meter T, Zagzag D, Jabado N, Schwartzentruber J, Majewski J, Scheetz TE, Pfister SM, Korshunov A, Li XN, Scherer SW, Cho YJ, Akagi K, MacDonald TJ, Koster J, McCabe MG, Sarver AL, Collins VP, Weiss WA, Largaespada DA, Collier LS, Taylor MD. Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature.
  • 2012 Feb 15;482(7386):529-33. doi: 10.1038/nature10825. PMID: 22343890
  • Bergemann TL, Starr TK, Yu H, Steinbach M, Erdmann J, Chen Y, Cormier RT, Largaespada DA, Silverstein KA. New methods for finding common insertion sites and co-occurring common insertion sites in transposon- and virus-based genetic screens. Nucleic Acids Res. 2012 Jan 12.
  • Wilber A, Ulloa Montoya F, Hammer L, Moriarity BS, Geurts AM, Largaespada DA, Verfaillie CM, McIvor RS, Lakshmipathy U. Efficient non-viral integration and stable gene expression in multipotent adult progenitor cells. Stem Cells Int. 2011;2011:717069. Epub 2011 Oct 2.
  • Wiesner SM, Geurts JL, Diers MD, Bergerson RJ, Hasz DE, Morgan KJ, Largaespada DA. Nf1 mutant mice with p19ARF gene loss develop accelerated hematopoietic disease resembling acute leukemia with a variable phenotype. Am J Hematol. 2011 Jul;86(7):579-85. doi: 10.1002/ajh.22035.
  • 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, and Largaespada DA. A transposon-based genetic screen in mice identifies genes altered in colorectal cancer. Science, 323(5922): 1747-50. (2009).
  • Starr TK, Scott PM, Marsh BM, Zhao L, Than BL, O'Sullivan MG, Sarver AL, Dupuy AJ, Largaespada DA, Cormier RT. A Sleeping Beauty transposon-mediated screen identifies murine susceptibility genes for adenomatous polyposis coli (Apc)-dependent intestinal tumorigenesis. Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5765-70. Epub 2011 Mar 21.
  • Keng VW, Tschida BR, Bell JB, Largaespada DA. Modeling hepatitis B virus X-induced hepatocellular carcinoma in mice with the Sleeping Beauty transposon system. Hepatology. 2011 Mar;53(3):781-90. doi: 10.1002/hep.24091. Epub 2011 Jan 3.
  • Bender AM, Collier LS, Rodriguez FJ, Tieu C, Larson JD, Halder C, Mahlum E, Kollmeyer TM, Akagi K, Sarkar G, Largaespada DA, Jenkins RB. Sleeping beauty-mediated somatic mutagenesis implicates CSF1 in the formation of high-grade astrocytomas. Cancer Res. 2010 May 1;70(9):3557-65. Epub 2010 Apr 13.
  • Hackett PB, Largaespada DA, Cooper LJ. A transposon and transposase system for human application. Mol Ther. 2010 Apr;18(4):674-83. Epub 2010 Jan 26. Review.
  • Collier LS, Adams DJ, Hackett CS, Bendzick LE, Akagi K, Davies MN, Diers MD, Rodriguez FJ, Bender AM, Tieu C, Matise I, Dupuy AJ, Copeland NG, Jenkins NA, Hodgson JG, Weiss WA, Jenkins RB, Largaespada DA. Whole-body sleeping beauty mutagenesis can cause penetrant leukemia/lymphoma and rare high-grade glioma without associated embryonic lethality. Cancer Res. 2009 Nov 1;69(21):8429-37. Epub 2009 Oct 20.
  • Keng VW, Ryan BJ, Wangensteen KJ, Balciunas D, Schmedt C, Ekker SC, Largaespada DA. Efficient transposition of Tol2 in the mouse germline. Genetics. 2009 Dec;183(4):1565-73. Epub 2009 Oct 5.
  • Johnson KJ, Springer NM, Bielinsky AK, Largaespada DA, Ross JA. Developmental origins of cancer. Cancer Res. 2009 Aug 15;69(16):6375-7. Epub 2009 Aug 4.
  • Largaespada DA. Transposon-mediated mutagenesis of somatic cells in the mouse for cancer gene identification. Methods. 2009 Nov;49(3):282-6. Epub 2009 Jul 14.
  • Rahrmann EP, Collier LS, Knutson TP, Doyal ME, Kuslak SL, Green LE, Malinowski RL, Roethe L, Akagi K, Waknitz M, Huang W, Largaespada DA, Marker PC. Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon-based somatic mutagenesis screen. Cancer Res. 2009 May 15;69(10):4388-97. Epub 2009 Apr 28.
  • Largaespada DA. Transposon mutagenesis in mice. Methods Mol Biol. 2009;530:379-90.
  • 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, and Largaespada DA. A transposon-based genetic screen in mice identifies genes altered in colorectal cancer. Science. 2009 Mar 27;323(5922):1747-50. Epub 2009 Feb 26.
  • 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, and Largaespada DA. A conditional transposon-based insertional mutagenesis screen for hepatocellular carcinoma-associated genes in mice. Nature Biotech. 2009 Mar;27(3):264-74. Epub 2009 Feb 22.
  • 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 Jan 15;69(2):431-9.