• Home
• Mischer Neuroscience Institute
• Education
• Faculty & Staff
• Research
• Careers

Assistant Professor, The Vivian L. Smith Department of Neurosurgery

Education & Training

• Undergraduate Degree:
  Virginia Polytechnic Institute and State University, Blacksburg, Virginia
• Doctor of Philosophy, Molecular, Cellular, and Developmental Biology:
  University of Pittsburgh, Pittsburgh, Pennsylvania

Research Interests

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.

Selected Bibliography

• 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. PMID: 22118463
• 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. PMID: 21962509
• 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. PMID: 22001392
• 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. PMID: 21185283
• Santanam, U., Zanesi, N., Efanov, A., Costinean, S., Palamarchuk, A., Hagan, J. P., Volinia, S., Alder, H., Rassenti, L., Kipps, T., Croce, C.M., Sharma, and Pekarsky, Y. (2010) Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. Proceedings National Academy of Science USA 107: 12210-12215. PMID: 20566844
• 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. PMID: 20404277
• 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. PMID: 19713958
• 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. PMID: 19351822
• 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. PMID: 19194500
• 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 domaincontaining oxidoreductase tumor suppressor leads to impaired steroidogenesis. Endocrinology 150: 1530-1535. PMID: 18974271
• 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. Gynecological Oncology 112: 55-59. PMID: 18954897
• 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. PMID: 20016602
• Taccioli, C., Gabbri, 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. PMID: 18945703
• 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. PMID: 18728182
• 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
• 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. PMID: 18487609
• 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
• Hagan, J. P. and Croce, C.M. (2007) MicroRNAs in Carcinogenesis. Cytogenetic and Genome Research 118: 252-259. PMID: 18000378
• 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
• 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. PMID: 17575124
• 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
• 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. PMID: 17360458
• 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
• 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
• 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
• 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
• 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