Adam Dupuy, PhD

Portrait
Associate Professor of Anatomy and Cell Biology
Associate Professor of Pathology

Contact Information

Primary Office: 3202 MERF
Iowa City, IA 52242
319-335-8090

Education

BA, Biology and Chemistry, Central College
PhD, Molecular, Cellular, Developmental Biology, and Genetics, University of Minnesota

Postdoctoral Fellow, University of Minnesota Cancer Center
Postdoctoral Fellow, Mouse Cancer Genetics, National Cancer Institute

Education/Training Program Affiliations

Department of Cell and Developmental Graduate Program, Interdisciplinary Graduate Program in Genetics, Interdisciplinary Graduate Program in Molecular Medicine, Medical Scientist Training Program

Research Summary

The goal of my current research is to understand the role that somatic mutation plays in all aspects of tumor biology. Much of our work has made use of the Sleeping Beauty (SB) transposon system to engineer mouse cancer models in which somatic mutations are generated by transposon insertions. We and our collaborators have recently described a variety of tumor models using the approach, and these studies have identified many novel candidate cancer genes. The current work in my laboratory focuses on the genetics of hepatocellular carcinoma and T-cell leukemia. In addition, we have ongoing collaborative efforts to develop SB models of ovarian and endometrial cancer. Future work in the lab will focus on using our mouse models to address relevant questions encountered by oncologists in the clinic (e.g. metastasis, drug resistance).

Publications

Ziyad, S., Riordan, J. D., Cavanaugh, A. M., Su, T., Hernandez, G. E., Hilfenhaus, G., Morselli, M., Huynh, K., Wang, K., Chen, J. N., Dupuy, A. J. & Iruela-Arispe, M. L. (2018). A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis. Cell Reports, 22(5), 1211-1224. PMID: 29386109.

Riordan, J. D., Feddersen, C. R., Tschida, B. R., Beckmann, P. J., Keng, V. W., Linden, M. A., Amin, K., Stipp, C. S., Largaespada, D. A. & Dupuy, A. J. (2018). Chronic liver injury alters driver mutation profiles in hepatocellular carcinoma in mice. Hepatology, 67(3), 924-939. PMID: 28961327.

Suárez-Cabrera, C., Quintana, R. M., Bravo, A., Casanova, M. L., Page, A., Alameda, J. P., Paramio, J. M., Maroto, A., Salamanca, J., Dupuy, A. J., Ramírez, A. & Navarro, M. (2017). A transposon-based analysis reveals RASA1 is involved in triple negative breast cancer. Cancer Research, 77(6), 1357-1368. PMID: 28108518.

Montero-Conde, C., Leandro-Garcia, L. J., Chen, X., Oler, G., Ruiz-Llorente, S., Ryder, M., Landa, I., Sanchez-Vega, F., La, K., Ghossein, R. A., Bajorin, D. F., Knauf, J. A., Riordan, J. D., Dupuy, A. J. & Fagin, J. A. (2017). Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene. Proceedings of the National Academy of Sciences of the United States of America, 114(25), E4951-E4960. PMID: 28584132.

Rauckhorst, A. J., Gray, L. R., Sheldon, R. D., Fu, X., Pewa, A. D., Feddersen, C. R., Dupuy, A. J., Gibson-Corley, K. N., Cox, J. E., Burgess, S. C. & Taylor, E. B. (2017). The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity. Molecular Metabolism, 6(11), 1468-1479. PMID: 29107293.

Temiz, N. A., Moriarity, B. S., Wolf, N. K., Riordan, J. D., Dupuy, A. J., Largaespada, D. A. & Sarver, A. L. (2016). RNA sequencing of Sleeping Beauty transposon-induced tumors detects transposon-RNA fusions in forward genetic cancer screens. Genome Research, 26(1), 119-129. PMID: 26553456.

Morrissy, A. S., Garzia, L., Shih, D. J., Zuyderduyn, S., Huang, X., Skowron, P., Remke, M., Cavalli, F. M., Ramaswamy, V., Lindsay, P. E., Jelveh, S., Donovan, L. K., Wang, X., Luu, B., Zayne, K., Li, Y., Mayoh, C., Thiessen, N., Mercier, E., Mungall, K. L., Ma, Y., Tse, K., Zeng, T., Shumansky, K., Roth, A. J., Shah, S., Farooq, H., Kijima, N., Holgado, B. L., Lee, J. J., Matan-Lithwick, S., Liu, J., Mack, S. C., Manno, A., Michealraj, K. A., Nor, C., Peacock, J., Qin, L., Reimand, J., Rolider, A., Thompson, Y. Y., Wu, X., Pugh, T., Ally, A., Bilenky, M., Butterfield, Y. S., Carlsen, R., Cheng, Y., Chuah, E., Corbett, R. D., Dhalla, N., He, A., Lee, D., Li, H. I., Long, W., Mayo, M., Plettner, P., Qian, J. Q., Schein, J. E., Tam, A., Wong, T., Birol, I., Zhao, Y., Faria, C. C., Pimentel, J., Nunes, S., Shalaby, T., Grotzer, M., Pollack, I. F., Hamilton, R. L., Li, X. N., Bendel, A. E., Fults, D. W., Walter, A. W., Kumabe, T., Tominaga, T., Collins, V. P., Cho, Y. J., Hoffman, C., Lyden, D., Wisoff, J. H., Garvin, Jr, J. H., Stearns, D. S., Massimi, L., Schüller, U., Sterba, J., Zitterbart, K., Puget, S., Ayrault, O., Dunn, S. E., Tirapelli, D. P., Carlotti, C. G., Wheeler, H., Hallahan, A. R., Ingram, W., MacDonald, T. J., Olson, J. J., Van Meir, E. G., Lee, J. Y., Wang, K. C., Kim, S. K., Cho, B. K., Pietsch, T., Fleischhack, G., Tippelt, S., Ra, Y. S., Bailey, S., Lindsey, J. C., Clifford, S. C., Eberhart, C. G., Cooper, M. K., Packer, R. J., Massimino, M., Garre, M. L., Bartels, U., Tabori, U., Hawkins, C. E., Dirks, P., Bouffet, E., Rutka, J. T., Wechsler-Reya, R. J., Weiss, W. A., Collier, L. S., Dupuy, A. J., Korshunov, A., Jones, D. T., Kool, M., Northcott, P. A., Pfister, S. M., Largaespada, D. A., Mungall, A. J., Moore, R. A., Jabado, N., Bader, G. D., Jones, S. J., Malkin, D., Marra, M. A. & Taylor, M. D. (2016). Divergent clonal selection dominates medulloblastoma at recurrence. Nature, 529(7586), 351-357. PMID: 26760213.

Guimarães-Young, A., Neff, T., Dupuy, A. J. & Goodheart, M. J. (2016). Conditional deletion of Sox17 reveals complex effects on uterine adenogenesis and function. Developmental Biology, 414(2), 219-227. PMID: 27102016.

Sun, X., Yu, W., Sanz Navarro, M., Sweat, M., Eliason, S., Sharp, T., Liu, H., Seidel, K., Zhang, L., Moreno, M., Lynch, T., Holton, N. E., Rogers, L., Neff, T., Goodheart, M. J., Michon, F., Klein, O. D., Chai, Y., Dupuy, A. J., Engelhardt, J. F., Chen, Z. & Amendt, B. A. (2016). Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal. Development, 143(22), 4115-4126. PMID: 27660324.

Thiel, W. H., Thiel, K. W., Flenker, K. S., Bair, T., Dupuy, A. J., McNamara, 2nd, J. O., Miller, F. J. & Giangrande, P. H. (2015). Cell-internalization SELEX: method for identifying cell-internalizing RNA aptamers for delivering siRNAs to target cells. Methods in Molecular Biology, 1218, 187-199. PMID: 25319652.

Smith, R. P., Riordan, J. D., Feddersen, C. R. & Dupuy, A. J. (2015). A Hybrid Adenoviral Vector System Achieves Efficient Long-Term Gene Expression in the Liver via piggyBac Transposition. Human Gene Therapy, 26(6), 377-385. PMID: 25808258.

Bard-Chapeau, E. A., Nguyen, A. T., Rust, A. G., Sayadi, A., Lee, P., Chua, B. Q., New, L. S., de Jong, J., Ward, J. M., Chin, C. K., Chew, V., Toh, H. C., Abastado, J. P., Benoukraf, T., Soong, R., Bard, F. A., Dupuy, A. J., Johnson, R. L., Radda, G. K., Chan, E. C., Wessels, L. F., Adams, D. J., Jenkins, N. A. & Copeland, N. G. (2014). Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model. Nature Genetics, 46(1), 24-32. PMID: 24316982.

Lim, L., Balakrishnan, A., Huskey, N., Jodari, M., Ng, R., Song, G., Cheung, S., Willenbring, H., Dupuy, A. J., Chen, X. & Goga, A. (2014). MiR-494 within an oncogenic microRNA megacluster regulates G1/S transition liver tumorigenesis through suppression of MCC. Hepatology, 59(1), 202-215. PMID: 23913442.

Gibson-Corley, K. N., Rogers, L. M., Goeken, A., Dupuy, A. J. & Meyerholz, D. K. (2014). Keratoacanthoma Pathobiology in Mouse Models. Diseases, 2(2), 106-119. PMID: 25309748.

Zhang, Z., Kim, K., Li, X., Moreno, M., Sharp, T., Goodheart, M. J., Safe, S., Dupuy, A. J. & Amendt, B. A. (2014). MicroRNA-26b represses colon cancer cell proliferation by inhibiting lymphoid enhancer factor 1 expression. Molecular Cancer Therapeutics(American Association for Cancer Research), 13(7), 1942-1951. PMID: 24785257.

Riordan, J. D., Drury, L. J., Smith, R. P., Brett, B. T., Rogers, L. M., Scheetz, T. E. & Dupuy, A. J. (2014). Sequencing methods and datasets to improve functional interpretation of sleeping beauty mutagenesis screens. BMC Genomics, 15, 1150. PMID: 25526783.

Riordan, J. D., Keng, V. W., Tschida, B. R., Scheetz, T. E., Bell, J. B., Podetz-Pedersen, K. M., Moser, C. D., Copeland, N. G., Jenkins, N. A., Roberts, L. R., Largaespada, D. A. & Dupuy, A. J. (2013). Identification of rtl1, a retrotransposon-derived imprinted gene, as a novel driver of hepatocarcinogenesis. PLoS Genetics, 9(4), e1003441. PMID: 23593033.

Quintana, R. M., Dupuy, A. J., Bravo, A., Casanova, M. L., Alameda, J. P., Page, A., Sánchez-Viera, M., Ramírez, A. & Navarro, M. (2013). A transposon-based analysis of gene mutations related to skin cancer development. The Journal of Investigative Dermatology, 133(1), 239-248. PMID: 22832494.

Keng, V. W., Sia, D., Sarver, A. L., Tschida, B. R., Fan, D., Alsinet, C., Solé, M., Lee, W. L., Kuka, T. P., Moriarity, B. S., Villanueva, A., Dupuy, A. J., Riordan, J. D., Bell, J. B., Silverstein, K. A., Llovet, J. M. & Largaespada, D. A. (2013). Sex bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR. Hepatology, 57(1), 120-130. PMID: 22899566.

DeZwaan-McCabe, D., Riordan, J. D., Arensdorf, A. M., Icardi, M. S., Dupuy, A. J. & Rutkowski, D. T. (2013). The stress-regulated transcription factor CHOP promotes hepatic inflammatory gene expression, fibrosis, and oncogenesis. PLoS Genetics, 9(12), e1003937. PMID: 24367269.

Rogers, L. M., Olivier, A. K., Meyerholz, D. K. & Dupuy, A. J. (2013). Adaptive immunity does not strongly suppress spontaneous tumors in a Sleeping Beauty model of cancer. Journal of Immunology, 190(8), 4393-4399. PMID: 23475219.

Zanesi, N., Balatti, V., Riordan, J., Burch, A., Rizzotto, L., Palamarchuk, A., Cascione, L., Lagana, A., Dupuy, A. J., Croce, C. M. & Pekarsky, Y. (2013). A Sleeping Beauty screen reveals NF-kB activation in CLL mouse model. Blood, 121(21), 4355-4358. PMID: 23591791.

DeZwaan-McCabe, D., Riordon, J. D., Arensdorf, A. M., Chikka, M. R., Icardi, M. S., Dupuy, A. J. & Rutkowski, D. T. (2013). The stress-regulated transcription factor CHOP promotes hepatocellular oncogenesis. PLoS Genet, 9(12), e1003937. PMID: 24367269.

Riordan, J. D., Dupuy, A. J. (2013). Domesticated transposable element gene products in human cancer. Mobile Genetic Elements, 3(5), e26693. PMID: 24251072.

Rogers, L. M., Riordan, J. D., Swick, B. L., Meyerholz, D. K. & Dupuy, A. J. (2013). Ectopic expression of Zmiz1 induces cutaneous squamous cell malignancies in a mouse model of cancer. The Journal of Investigative Dermatology, 133(7), 1863-1869. PMID: 23426136.

Mann, K. M., Ward, J. M., Yew, C. C., Kovochich, A., Dawson, D. W., Black, M. A., Brett, B. T., Sheetz, T. E., Dupuy, A. J., Chang, D. K., Biankin, A. V., Waddell, N., Kassahn, K. S., Grimmond, S. M., Rust, A. G., Adams, D. J., Jenkins, N. A. & Copeland, N. G. (2012). Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma. Proceedings of the National Academy of Sciences of the United States of America, 109(16), 5934-5941. PMID: 22421440.

Wu, X., Northcott, P. A., Dubuc, A., Dupuy, A. J., Shih, D. J., Witt, H., Croul, S., Bouffet, E., Fults, D. W., Eberhart, C. G., Garzia, L., Van Meter, T., Zagzag, D., Jabado, N., Schwartzentruber, J., Majewski, J., Scheetz, T. E., Pfister, S. M., Korshunov, A., Li, X. N., Scherer, S. W., Cho, Y. J., Akagi, K., MacDonald, T. J., Koster, J., McCabe, M. G., Sarver, A. L., Collins, V. P., Weiss, W. A., Largaespada, D. A., Collier, L. S. & Taylor, M. D. (2012). Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature, 482(7386), 529-33. PMID: 22343890.

Berquam-Vrieze, K. E., Swing, D. A., Tessarollo, L. & Dupuy, A. J. (2012). Characterization of transgenic mice expressing cancer-associated variants of human NOTCH1. Genesis, 50(2), 112-118. PMID: 21898766.

Brett, B. T., Berquam-Vrieze, K. E., Nannapaneni, K., Huang, J., Scheetz, T. E. & Dupuy, A. J. (2011). Novel molecular and computational methods improve the accuracy of insertion site analysis in Sleeping Beauty-induced tumors. PloS one, 6(9), e24668. PMID: 21931803.

McGrail, M., Hatler, J. M., Kuang, X., Liao, H. K., Nannapaneni, K., Watt, K. E., Uhl, J. D., Largaespada, D. A., Vollbrecht, E., Scheetz, T. E., Dupuy, A. J., Hostetter, J. M. & Essner, J. J. (2011). Somatic mutagenesis with a Sleeping Beauty transposon system leads to solid tumor formation in zebrafish. PloS one, 6(4), e18826. PMID: 21533036.

Starr, T. K., Scott, P. M., Marsh, B. M., Zhao, L., Than, B. L., O'Sullivan, M. G., Sarver, A. L., Dupuy, A. J., Largaespada, D. A. & Cormier, R. T. (2011). A Sleeping Beauty transposon-mediated screen identifies murine susceptibility genes for adenomatous polyposis coli (Apc)-dependent intestinal tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America, 108(14), 5765-70. PMID: 21436051.

Berquam-Vrieze, K. E., Nannapaneni, K., Brett, B. T., Holmfeldt, L., Ma, J., Zagorodna, O., Jenkins, N. A., Copeland, N. G., Meyerholz, D. K., Knudson, C. M., Mullighan, C. G., Scheetz, T. E. & Dupuy, A. J. (2011). Cell of origin strongly influences genetic selection in a mouse model of T-ALL. Blood, 118(17), 4646-56. PMID: 21828136.

Thiel, W. H., Bair, T., Wyatt Thiel, K., Dassie, J. P., Rockey, W. M., Howell, C. A., Liu, X. Y., Dupuy, A. J., Huang, L., Owczarzy, R., Behlke, M. A., McNamara, J. O. & Giangrande, P. H. (2011). Nucleotide bias observed with a short SELEX RNA aptamer library. Nucleic acid therapeutics, 21(4), 253-63. PMID: 21793789.

Dupuy, A. J. (2010). Current applications of transposons in mouse genetics. Methods in enzymology, 477, 53-70. PMID: 20699136.

Wang, D. H., Clemons, N. J., Miyashita, T., Dupuy, A. J., Zhang, W., Szczepny, A., Corcoran-Schwartz, I. M., Wilburn, D. L., Montgomery, E. A., Wang, J. S., Jenkins, N. A., Copeland, N. A., Harmon, J. W., Phillips, W. A. & Watkins, D. N. (2010). Aberrant epithelial-mesenchymal Hedgehog signaling characterizes Barrett's metaplasia. Gastroenterology, 138(5), 1810-22. PMID: 20138038.

Dupuy, A. J. (2010). Transposon-based screens for cancer gene discovery in mouse models. Seminars in cancer biology, 20(4), 261-8. PMID: 20478384.

Starr, T. K., Allaei, R., Silverstein, K. A., Staggs, R. A., Sarver, A. L., Bergemann, T. L., Gupta, M., O'Sullivan, M. G., Matise, I., Dupuy, A. J., Collier, L. S., Powers, S., Oberg, A. L., Asmann, Y. W., Thibodeau, S. N., Tessarollo, L., Copeland, N. G., Jenkins, N. A., Cormier, R. T. & Largaespada, D. A. (2009). A transposon-based genetic screen in mice identifies genes altered in colorectal cancer. Science (New York, N.Y.), 323(5922), 1747-50. PMID: 19251594.

Keng, V. W., Villanueva, A., Chiang, D. Y., Dupuy, A. J., Ryan, B. J., Matise, I., Silverstein, K. A., Sarver, A., Starr, T. K., Akagi, K., Tessarollo, L., Collier, L. S., Powers, S., Lowe, S. W., Jenkins, N. A., Copeland, N. G., Llovet, J. M. & Largaespada, D. A. (2009). A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma. Nature biotechnology, 27(3), 264-74. PMID: 19234449.

Dupuy, A. J., Rogers, L. M., Kim, J., Nannapaneni, K., Starr, T. K., Liu, P., Largaespada, D. A., Scheetz, T. E., Jenkins, N. A. & Copeland, N. G. (2009). A modified sleeping beauty transposon system that can be used to model a wide variety of human cancers in mice. Cancer research, 69(20), 8150-6. PMID: 19808965.

Collier, L. S., Adams, D. J., Hackett, C. S., Bendzick, L. E., Akagi, K., Davies, M. N., Diers, M. D., Rodriguez, F. J., Bender, A. M., Tieu, C., Matise, I., Dupuy, A. J., Copeland, N. G., Jenkins, N. A., Hodgson, J. G., Weiss, W. A., Jenkins, R. B. & Largaespada, D. A. (2009). Whole-body sleeping beauty mutagenesis can cause penetrant leukemia/lymphoma and rare high-grade glioma without associated embryonic lethality. Cancer research, 69(21), 8429-37. PMID: 19843846.

Su, Q., Prosser, H. M., Campos, L. S., Ortiz, M., Nakamura, T., Warren, M., Dupuy, A. J., Jenkins, N. A., Copeland, N. G., Bradley, A. & Liu, P. (2008). A DNA transposon-based approach to validate oncogenic mutations in the mouse. Proceedings of the National Academy of Sciences of the United States of America, 105(50), 19904-9. PMID: 19064922.

Dupuy, A. J., Jenkins, N. A. & Copeland, N. G. (2006). Sleeping beauty: a novel cancer gene discovery tool. Human molecular genetics, 15 Spec No 1, R75-9. PMID: 16651372.

Collier, L. S., Carlson, C. M., Ravimohan, S., Dupuy, A. J. & Largaespada, D. A. (2005). Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature, 436(7048), 272-6. PMID: 16015333.

Dupuy, A. J., Akagi, K., Largaespada, D. A., Copeland, N. G. & Jenkins, N. A. (2005). Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system. Nature, 436(7048), 221-6. PMID: 16015321.

Geurts, A. M., Yang, Y., Clark, K. J., Liu, G., Cui, Z., Dupuy, A. J., Bell, J. B., Largaespada, D. A. & Hackett, P. B. (2003). Gene transfer into genomes of human cells by the sleeping beauty transposon system. Molecular therapy : the journal of the American Society of Gene Therapy, 8(1), 108-17. PMID: 12842434.

Carlson, C. M., Dupuy, A. J., Fritz, S., Roberg-Perez, K. J., Fletcher, C. F. & Largaespada, D. A. (2003). Transposon mutagenesis of the mouse germline. Genetics, 165(1), 243-56. PMID: 14504232.

Belur, L. R., Frandsen, J. L., Dupuy, A. J., Ingbar, D. H., Largaespada, D. A., Hackett, P. B. & Scott McIvor, R. (2003). Gene insertion and long-term expression in lung mediated by the Sleeping Beauty transposon system. Molecular therapy : the journal of the American Society of Gene Therapy, 8(3), 501-7. PMID: 12946324.

Dupuy, A. J., Clark, K., Carlson, C. M., Fritz, S., Davidson, A. E., Markley, K. M., Finley, K., Fletcher, C. F., Ekker, S. C., Hackett, P. B., Horn, S. & Largaespada, D. A. (2002). Mammalian germ-line transgenesis by transposition. Proceedings of the National Academy of Sciences of the United States of America, 99(7), 4495-9. PMID: 11904379.

Dupuy, A. J., Morgan, K., von Lintig, F. C., Shen, H., Acar, H., Hasz, D. E., Jenkins, N. A., Copeland, N. G., Boss, G. R. & Largaespada, D. A. (2001). Activation of the Rap1 guanine nucleotide exchange gene, CalDAG-GEF I, in BXH-2 murine myeloid leukemia. The Journal of biological chemistry, 276(15), 11804-11. PMID: 11278453.

Dupuy, A. J., Fritz, S. & Largaespada, D. A. (2001). Transposition and gene disruption in the male germline of the mouse. Genesis (New York, N.Y. : 2000), 30(2), 82-8. PMID: 11416868.

Li, J., Shen, H., Himmel, K. L., Dupuy, A. J., Largaespada, D. A., Nakamura, T., Shaughnessy, Jr, J. D., Jenkins, N. A. & Copeland, N. G. (1999). Leukaemia disease genes: large-scale cloning and pathway predictions. Nature genetics, 23(3), 348-53. PMID: 10610183.