Biography

Dr. Hagan received his Ph.D. from the University of Pittsburgh under the mentorship of the HHMI Investigator Dr. Paula Grabowski where his research focused on elucidating the molecular mechanisms responsible for exon definition during pre-mRNA alternative splicing.

His initial postdoctoral training occurred in Dr. Colin Stewart’s lab at the National Cancer Institute investigating the role of imprinted genes in mammalian development and cancer.

Afterward, he joined the lab of Dr. Carlo Croce, a member of both the National Academy of Science and Institute of Medicine, where Dr. Hagan co-authored a number of high impact papers defining the role of microRNAs in cancer. He then received additional training at Children’s Hospital Boston/Harvard Medical School, studying post-transcriptional regulation of microRNA biogenesis and function where LIN28/let-7 pathway was of particular interest. In 2012, Dr. Hagan joined the Department of Neurosurgery as an Assistant Professor.

Education

Post Graduate School
University of Pittsburgh, Pittsburgh, Pennsylvania (Molecular, Cellular, and Developmental Biology)

Research Information

My research focuses on understanding the role of microRNAs and their post-transcriptional regulators in developmental and cancer biology. We and others have shown that microRNA expression is dysregulated in cancer and demonstrated using mouse models a direct role for these non-coding, regulatory RNAs in cancer initiation, progression, and metastasis. In addition, we are continuing our research efforts to delineate the importance of 3’ RNA polyuridylation in gene regulation, as we have recently described a Terminal Uridylyl Transferase (TUTase) named Zcchc11 that works with Lin28A to block biogenesis of the tumor suppressor let-7 microRNA family. My cancer studies focus primarily on types characterized by Lin28A/Lin28B overexpression and let-7 loss such as medulloblastoma, neuroblastoma, atypical teratoid rhabdoid tumors, and breast adenocarcinoma. Efforts are ongoing to screen for modifiers of the Lin28/let-7 pathway that may hold therapeutic potential in cancer and type 2 diabetes.

Publications

Publication Information

RECENT PUBLICATIONS (since 2004)

  1. Cui, X., Zhang, Y., Yang, J., Sun, X., Hagan, J.P., Guha, S., and Li, M. (2014) ZIP4 confers resistance to zinc deficiency-induced apoptosis in pancreatic cancer. Cell Cycle 13(7): 1180-1196 PMCID: PMC4013168
  2. Zhang, Y., Yang, J., Cui, X., Chen, Y., Zhu, V.F., Hagan, J.P., Wang, H., Yu, X., Hodges, S.E., Fang, J., Chiao, P.J., Logsdon, C.D., Fisher, W.E., Brunicardi, F.C., Chen, C., Yao, Q., Fernandez-Zapico, M.E., and Li. M. (2013) A novel epigenetic CREB-miR-373 axis mediates ZIP4-induced pancreatic cancer growth. EMBO Molecular Medicine 5:1322-1334 PMCID: PMC3799489
  3. Shinoda, G., Shyh-Chang, N., de Soysa, T.Y., Zhu, H., Seligson, M.T., Shah, S.P., Abo-Sido, N., Yabuuchi, A., Hagan, J.P., Gregory, R.I., Asara, J.M., Cantley, L.C., Moss, E.G., and Daley, G.Q. (2013) Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism. Stem Cells 31:1563-1573 PMCID: PMC3775935
  4. Chen, L., Zhang, Y., Yang, J., Hagan, J.P., and Li, M. (2013) Vertebrate Animal Models of Glioma: Understanding the Mechanisms and Developing New Therapies.  Biochimica et Biophysica Acta-Reviews on Cancer doi: 10.1016/j.bbcan.2013.04.003 PMCID: PMC372903
  5. Shinoda, G., de Soysa, T.Y., Seligson, M.T., Yabuuchi, A., Fujiwara, Y., Huang, P.Y., Hagan, J.P., Gregory, R.I., Moss, E.G., and Daley, G.Q. (2013) Lin28a regulates germ cell pool size and fertility.  Stem Cells 31:1001-1009 PMCID: PMC3652309
  6. Abdeen, S.K., Del Mare, S., Hussain, S., Remaileh, M.A., Salah, Z., Hagan, J., Rawahneh, M., Pu, X.A., Russell, S., Stein, J.L., Stein, G.S., Lian, J.B.,  and Aqeilan, R.I. (2013) Conditional inactivation of the mouse WWOX tumor suppressor gene recapitulates the null phenotype.  Journal of Cellular Physiology 228:1377-1382 PMID: 23254685
  7. Chang, H.M., Martinez, N.J., Thornton, J.E., Hagan, J.P., Nguyen, K.D., and Gregory, R.I. (2012) Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation.  Nature Communications 3: 923 PMCID: PMC3518406
  8. Piskounova, E., Polytarchou, C., Thornton, J.E., LaPierre, R.J., Pothoulakis, C., Hagan, J. P., Iliopoulos, D., and Gregory, R.I. (2011) Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms.  Cell 147: 1066-1079. PMCID: PMC3227872
  9. Zhu, H., Shyh-Chang, N., Segrè, A.V., Shinoda, G., Shah, S.P., Einhorn, W.S., Takeuchi, A., Engreitz, J.M, Hagan, J.P., Kharas, M.G., Urbach, A., Thornton, J.E., Triboulet, R., Gregory, R.I., DIAGRAM Consortium, MAGIC Investigators, Altshuler, D., and Daley, G.Q. (2011) The Lin28/let-7 axis regulates glucose metabolism.  Cell 147: 81-94. PMCID: PMC3353524
  10. Motiwala, T., Zanesi, N., Datta, J., Roy, S., Kutay, H., Checovich, A.M., Kaou, M., Zhong, Y., Johnson, A.J., Lucas, D.M., Heerema, N.A., Hagan, J., Mo, X., Jarjoura, D., Byrd, J.C., Croce, C.M., and Jacob. S.T. (2011) AP-1 elements and TCL1 protein regulate expression of the gene encoding protein tyrosine phosphatase PTPROt in leukemia.  Blood 118: 6132-6140 PMCID: PMC3234669
  11. Wenzel, P.L., Chong, J.L., Saenz-Robles, M.T., Ferrey, A., Hagan, J.P., Gomez, Y.M., Rajmohan, R., Sharma, N., Chen, H.Z., Pipas, J.M., Robinson, M.L., and Leone, G. (2011) Cell proliferation in the absence of E2F1-3.  Developmental Biology 351: 35-45. PMCID: PMC3868453
  12. Santanam, U., Zanesi, N., Efanov, A., Costinean, S., Palamarchuk, A., Hagan, J.P., Volinia, S., Alder, H., Rassenti, L., Kipps, T., Croce, C.M., and Pekarsky, Y. (2010) Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression.  Proceedings National Academy of Science USA 107: 12210-12215. PMCID: PMC2901490
  13. Liu, J.Q., Joshi, P.S., Wang, C., El-Omrani, H.Y., Xiao, Y., Liu, X.P., Hagan, J.P., Liu, C.G., Wu, L.C., and Bai, X.F. (2010) Targeting activation-induced cytidine deaminase overcome tumor evasion of immunotherapy by CTLs.  Journal of Immunology 184: 5435-5443. PMCID: PMC2874093
  14. Hagan, J.P.#, Piskounova, E.#, and Gregory, R.I. (2009) Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells.  Nature Structural & Molecular Biology 16: 1021-1025. PMCID: PMC2758923
  15. Northcott, P.A.#, Fernandez-L, A.#, Hagan, J.P.#, Ellison, D.W., Grajkowska, W., Gillespie, Y., Grundy, R., Van Meter, T., Rutka, J.T., Croce, C.M., Kenney, A.M., and Taylor, M.D. (2009) The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors.  Cancer Research 69: 3249-3255. PMCID: PMC2836891
  16. Hagan, J.P., O’Neill, B.L., Stewart, C.L., Kozlov, S.V., and Croce, C.M. (2009) At least ten genes define the imprinted Dlk1-Dio3 cluster on mouse chromosome 12qF1.  PLoS One 4: e4352. PMCID: PMC2632752
  17. Aqeilan, R.I., Hagan, J. P., de Bruin, A., Rawahneh, M., Salah, Z., Gaudio, E., Siddiqui, H. Volinia, S., Alder, H., Lian, J.B., Stein, G.S., and Croce, C.M. (2009) Target ablation of the WW domain-containing oxidoreductase tumor suppressor leads to impaired steroidogenesis.  Endocrinology 150: 1530-1535. PMCID: PMC2654736
  18. Resnick, K.E., Alder, H., Hagan, J.P., Richardson, D.L., Croce, C.M., and Cohn, D.E. (2009) The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecologic Oncology 112: 55-59. PMID: 18954897
  19. Chong, J.L., Wenzel, P.L., Saenz-Robles, M.T., Nair, V., Ferrey, A., Hagan, J.P., Gomez, Y.M., Sharma, N., Chen, H.Z., Ouseph, M., Wang, S.H., Trikha, P., Culp, B., Mezache, L., Winton, D.J., Sansom, O.J., Chen, D.N., Bremner, R., Cantalupo, P.G., Robinson, M.L., Pipas, J.M., and Leone, G. (2009) E2f1–3 switch from activators in progenitor cells to repressors in differentiating cells.  Nature 462: 934-1025. PMCID: PMC2806193
  20. Taccioli, C., Fabbri, E., Visone, R., Volinia, S., Calin, G.A., Fong, L.Y., Gambari, R., Bottoni, A., Acunzo, M., Hagan, J., Iorio, M.V., Piovan, C., Romano, G., and Croce, C.M. (2009) UCbase & miRfunc: a database of ultraconserved sequences and microRNA function.  Nucleic Acids Research 37: D41-48. PMCID: PMC2686429
  21. Pichiorri, F., Suh, S.S., Ladetto, M., Kuehl, M., Palumbo,T., Drandi, D., Taccioli, C., Zanesi, N., Alder, H., Hagan, J.P., Munker, R., Volinia, S., Boccadoro, M., Garzon, R., Palumbo, A., Aqeilan, R.I., and Croce, C.M. (2008) MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis.  Proceedings National Academy of Science USA 105: 12885-12890. PMCID: PMC2529070
  22. Rao, Y, Lee, Y., Jarjoura, D., Ruppert, A.S., Hsu, J.C., and  Hagan, J.P. (2008) A Comparison of Normalization Techniques for MicroRNA Microarray Data.  Statistical Applications in Genetics and Molecular Biology, 7: Article 22. PMID: 18673291
  23. Aqeilan, R.I., Hassan, M.Q., de Bruin, A., Hagan, J.P., Volinia, S., Palumbo, T., Hussain, S., Lee, S.H., Gaur, T., Stein, G.S., Lian, J.B., and Croce, C.M. (2008) The WWOX tumor suppressor is essential for post-natal survival and normal bone metabolism.  Journal of Biological Chemistry 283: 21629-21639. PMCID: PMC2490770
  24. Schmid, T., Jansen, A.P., Baker, A.R., Hegamyer, G., Hagan, J.P., and Colburn, N.H. (2008) Tumor suppressor Pdcd4 is targeted during tumor promotion.  Cancer Research 68: 1254-1260. PMID: 18296647
  25. Hagan, J.P. and Croce, C.M. (2007) MicroRNAs in Carcinogenesis. Cytogenetic and Genome Research 118: 252-259. PMID: 18000378
  26. Kebache, S., Ash, J., Annis, M.G., Hagan, J., Huber, M., Hassard, J., Stewart, C.L., Whiteway, M., and Nantel, A. (2007) Grb10 and active Raf-1 kinase promote bad-dependent cell survival. Journal of Biological Chemistry 282: 21873-21883. PMID: 17535812 Free Full Text
  27. Aqeilan, R.I, Hagan, J.P., Aqeilan, H.A., Petrocca, F., Fong, L.Y., and Croce, C.M. (2007) Inactivation of the Wwox gene accelerates forestomach tumor progression in vivo. Cancer Research 67: 5606-5610. PMCID: PMC2621009
  28. Bloomston, M., Frankel, W.L., Petrocca, F., Volinia, S., Alder, H., Hagan, J.P., Liu, C.G., Bhatt, D., Taccioli, C., and Croce, C.M. (2007) MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. Journal of the American Medical Association 297: 1901-1908. PMID: 18296647
  29. Aqeilan, R.I, Trapasso, F., Hussain, S., Costinean, S., Pekarsky, Y., Hagan, J.P., Zanesi, N., Kaou, M., Stein, G.S., Lian, J.B., and Croce, C.M. (2007) Targeted deletion of WWOX reveals a tumor suppressor function. Proceedings National Academy of Science USA 104: 3949-3954. PMCID: PMC1820689
  30. Pekarsky, Y., Santanam, U., Cimmino, A., Palamarchuk, A., Efanov, A., Maximov, V., Volinia, S., Alder, H., Liu, C.G., Rassenti, L., Calin, G.A., Kipps, T., Hagan, J.P., and Croce, C.M. (2006) Tcl1 expression in CLL is regulated by miR-29 and miR-181. Cancer Research 66: 11590-11593. PMID: 17178851 Free Full Text
  31. Roldo, C., Missiaglia, E., N., Hagan, J.P., Falconi, M., Capelli, P., Bersani, S., Calin, G.A., Volinia, S., Liu, C.G., Scarpa, A., and Croce, C.M. (2006) MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior.  Journal of Clinical Oncology 24: 4677-4684. PMID: 16966691
  32. Palamarchuk, A., Zanesi, N., Aqeilan, R.I., Efanov, A., Maximov, V., Santanam, U., Hagan, J.P., Croce, C.M., and Pekarsky, Y. (2006) Tal1 transgenic expression reveals absence of B lymphocytes.  Cancer Research 66: 6014-6017. PMID: 16778172 Free Full Text
  33. Fan, T., Hagan, J.P., Kozlov, S.V., Stewart, C.L., and Muegge, K. (2005) Lsh Controls Silencing of the Imprinted Cdkn1c Gene. Development 132: 635-644. PMID: 15647320 Free Full Text
  34. Hagan, J.P., Sewell, L., Kozlov, S.V., Chiang, Y., and Stewart, C.L. (2004) Intraspecific Mating With CzechII/Ei Mice Rescue Lethality Associated With Loss of Function Mutations of the Imprinted Genes, Igf2r and Cdkn1c. Genomics 85: 835-843. PMID: 16778172