David A. Largaespada, PhD

Professor, Department of Pediatrics

David A. Largaespada

Contact Info

larga002@umn.edu

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

Administrative Email
godar009@umn.edu

Professor, Department of Pediatrics

Professor, Department of Genetics, Cell Biology and Development

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 Genetics, Cell Biology and Development

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

Advising Faculty, Graduate Program in Neuroscience


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

Summary

Dr. David Largaespada, Ph.D., is a Full Professor in the Departments of Pediatrics and Genetics, Cell Biology and Development and the Associate Director for Basic Research in the Masonic Cancer Center at University of Minnesota. He is an authority on mouse genetics, gene modification and cancer genes. He received his B.S. in Genetics and Cell Biology from the University of Minnesota, Twin Cities in 1987 and his Ph.D. in Molecular Biology with Dr. Rex Risser at the University of Wisconsin-Madison in 1992. He did a postdoctoral fellowship at the National Cancer Institute working with world-renowned geneticists Dr. Nancy Jenkins and Dr. Neal Copeland, where the Leukemia and Lymphoma Society of America awarded him a postdoctoral fellowship. He joined the faculty of the University of Minnesota in late 1996. Dr. Largaespada currently holds the Hedberg Family/Children’s Cancer Research Fund Chair in Brain Tumor Research. He was awarded the American Cancer Society Research Professor Award in 2013, the highest award given by the ACS.

Awards & Recognition

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

Research

Research Summary/Interests

Cancer genetics, Neurofibromatosis type 1 (Nf1), RAS signaling, insertional mutagenesis, pediatric cancer, brain tumors, osteosarcoma, transposons, Sleeping Beauty

Dr. Largaespada's laboratory is working to exploit insertional mutagenesis, and other functional genomics methods (e.g. CRISPR/Cas9) to identify and understand genes and pathways that govern cancer cell behavior. The Largaespada lab pioneered the use of a vertebrate-active transposon system, called Sleeping Beauty (SB), for insertional mutagenesis in mouse somatic cells. SB is being used as a tool for forward genetic screens for cancer genes involved in sarcoma, hepatocellular carcinoma, and mammary, gastro-intestinal tract and NF1 syndrome-associated nervous system cancers. A special emphasis of this work is on genes that promote metastasis or govern treatment sensitivity. Also, novel mouse models are being used for preclinical evaluation of new drugs and drug combinations for cancer treatment.

Research Methods/Techniques

Molecular biology, Mutagenesis, Transposons, Targeted nucleases, Cell culture, Ras signaling, Mouse transgenesis, Genetically engineered mouse and xenograft cancer models.

Publications

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

  • Kabriaei P, Singh H, Huls MH, Figliola MJ, Bassett R, Olivares S, Jena B, Dawson MJ, Kumaresan PR, Su S, Maiti S, Dai J, Moriarity B, Forget MA, Senyukov V, Orozco A, Liu T, McCarty J, Jackson RN, Moyes JS, Rondon G, Qazilbash M, Ciurea S, Alousi A, Nieto Y, Rezvani K, Marin D, Popat U, Kosing C, Shpall EJ, Kantarjian H, Keating M, Wierda W, Do KA, Largaespada DA, Lee DA, Hackett PB, Champlin RE, Cooper LJ. Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J Clin Invest. 2016 Sep 1; 126(9):3363-76. PMCID: PMC5004935
  • Wu J, Keng VW, Patmore DM, Kendall JJ, Patel AV, Jousma E, Jessen WJ, Choi K, Tschida BR, Silverstein KA, Ran D, Schwartz EB, Fuchs JR, Zou Y, Kim MO, Dombi E, Levy DE, Huang G, Cancelas JA, Stemmer-Rachamimov AO, Spinner RJ, Largaespada DA, Ratner N. Insertional Mutagenesis Identifies a STAT3/Arid1b/?-catenin Pathway Driving Neurofibroma Initiation. Cell Rep. 2016 Mar 1; 14(8):1979-90. PMCID: PMC4782770
  • Morrissy AS, Garzia L, Shih DJ, Zuyderduyn S, Huang X, Skowron P, Remke M, Cavalli FM, Ramaswamy V, Lindsay PE, Jelveh S, Donovan LK, Wang X, Luu B, Zayne K, Li Y, Mayoh C, Thiessen N, Mercier E, Mungall KL, Ma Y, Tse K, Zeng T, Shumansky K, Roth AJ, Shah S, Farooq H, Kijima N, Holgado BL, Lee JJ, Matan-Lithwick S, Liu J, Mack SC, Manno A, Michealraj KA, Nor C, Peacock J, Qin L, Reimand J, Rolider A, Thompson YY, Wu X, Pugh T, Ally A, Bilenky M, Butterfield YS, Carlsen R, Cheng Y, Chuah E, Corbett RD, Dhalla N, He A, Lee D, Li HI, Long W, Mayo M, Plettner P, Qian JQ, Schien JE, Tam A, Wong T, Birol I, Zhao Y, Faria CC, Pimentel J, Nunes S, Shalaby T, Grotzer M, Pollack IF, Hamilton RL, Li XN, Bendel AE, Fults DW, Walter AW, Kumabe T, Tominaga T, Collins VP, Cho YJ, Hoffman C, Lyden D, Wisoff JH, Garvin JH Jr, Stearns DS, Massimi L, Schuller U, Sterba J, Zitterbart K, Puget S, Ayrault O, Dunn SE, Tirapelli DP, Carlotti CG, Wheeler H, Hallahan AR, Ingram W, MacDonald TJ, Olson JJ, Van Meir EG, Lee JY, Wang KC, Kim SK, Cho BK, Pietsch T, Fleischhack G, Tippelt S, Ra YS, Bailey S, Lindsey JC, Clifford SC, Eberhart CG, Cooper MK, Packer RJ, Massimino M, Garre ML, Bartels U, Tabori U, Hawkins CE, Dirks P, Bouffet E, Rutka JT, Wechsler-Reya RJ, Weiss WA, Collier LS, Dupuy AJ, Korshunov A, Jones DT, Kool M, Northcott PA, Pfister SM, Largaespada DA, Mungall AJ, Moore RA, Japado N, Bader GD, Jones SJ, Malkin D, Marra MA, Taylor MD. Divergent clonal selection dominates medulloblastoma at recurrence. Nature. 2016 Jan 21; 529(7586):351-7. PMCID: PMC4936195
  • Moriarity BS, Otto GM, Rahrmann EP, Rathe SK, Wolf NK, Weg NK, Weg MT, Manlove LA, LaRue RS, Temiz NA, Molyneux SD, Choi K, Holly KJ, Sarver AL, Scott MC, Forster CL, Modiano JF, Khanna C, Hewitt SM, Khokha R, Yang Y, Gorlick R, Dyer MA, Largaespada DA. A Sleeping Beauty Forward Genetic Screen Identifies New Genes and Pathways Driving Osteosarcoma Development and Metastasis. Nat Genet. 2015 Jun; 47(6):615-24. PMCID: PMC4767150
  • Sachs Z, LaRue RS, Nguyen HT, Sachs K, Noble KE, Mohd Hassan NA, Diaz-Flores E, Rathe SK, Sarver AL, Bendall SC, Ha NA, Diers MD, Nolan GP, Shannon KM, Largaespada DA. NRASG12V oncogene facilitates self renewal in a murine model of acute myelogenous leukemia. Blood. 2014 Nov 20; 124(22): 3274-83. PMCID: PMC4239336
  • Tseng YY, Moriarity BS, Gong W, Akiyama R, Tiwari A, Kawakami H, Ronning P, Reuland B, Guenther K, Beadnell TC, Essig J, Otto GM, O'Sullivan MG, Largaespada DA, Schwertfeger KL, Marahrens Y, Kawakami Y, Bagchi A. PVT1 dependence in cancer with MYC copy-number increase. Nature. 2014 Aug 7; 512(7512):82-6. PMCID: PMC4767149
  • Rahrmann EP, Watson AL, Keng VW, Choi K, Moriarity BS, Beckmann DA, Wolf NK, Sarver A, Collins MH, Moertel CL, Wallace MR, Gel B, Serra E, Ratner N, Largaespada DA. Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis. Nat Genet. 2013 Jul; 45(7):756-66. PMCID: PMC3695033
  • Watson AL, Rahrmann EP, Moriarity BS, Choi K, Conboy CB, Greeley AD, Halfond AL, Anderson LK, Wahl BR, Keng VW, Rizzardi AE, Forster CL, Collins MH, Sarver AL, Wallace MR, Schmechel SC, Ratner N, Largaespada DA. Canonical Wnt/?-catenin signaling drives human Schwann cell transformation, progression, and tumor maintenance. Cancer Discov. 2013 Jun; 3(6):674-689. PMCID: PMC3679355
  • 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 30; 488(7413):660-4. PMCID: PMC3690621
  • 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 Jul 1; 72(13):3405-13. PMCID: PMC3428071
  • Starr TK, Allaei R, Silverstein KA, Staggs RA, Sarver AL, 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 Mar 27; 323(5922):1747-50. PMCID: PMC2743559
  • Keng VW, Villanueva A, Chiang DY, Dupuy A, Ryan BJ, Matise I, Silverstein KA, Sarver A, Starr TK, Akagi K, Tessarollo L, Collier LS, Powers S, Lowe SW, Jenkins NA, Copeland NG, Llovet JM, Largaespada DA. 2009. A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma. Nat Biotechnol. 2009 Mar; 27(3):264-274. PMCID: PMC2712727
  • Kim WI, Matise I, Diers MD, Largaespada DA. RAS oncogene suppression induces apoptosis followed by more differentiated and less myelosuppressive disease upon relapse of acute myeloid leukemia. Blood. 2009 Jan 29; 113(5):1086-96. PMCID: PMC2635074
  • Kim A, Morgan K, Hasz DE, Wiesner SM, Lauchle JO, Geurts JL, Diers MD, Le DT, Kogan SC, Parada LF, Shannon K, Largaespada DA. Beta common receptor inactivation attenuates myeloproliferative disease in Nf1 mutant mice. Blood. 2007 Feb 15; 109(4):1687-91. PMCID: PMC1794059
  • 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 Jul 14; 436(7048):272-6. PMID: 16015333
  • Largaespada DA, Brannan CI, Jenkins NA, Copeland NG. Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nat Genet. 1996 Feb; 12(2):137-43. PMID: 8563750