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.

他最初的博士后培训发生在国家癌症研究所的科林·斯图尔特（Colin Stewart）博士的实验室，研究了印迹基因在哺乳动物发育和癌症中的作用。

之后，他加入了美国国家科学院医学院和医学研究所的成员卡洛·克罗斯（Carlo Croce）博士的实验室，哈根博士在那里合着了许多高影响力论文，这些论文定义了microRNA在癌症中的作用。然后，他在波士顿儿童医院/哈佛医学院接受了额外的培训，研究了MicroRNA生物发生和功能的转录后调节，其中LIN28/LET-7途径特别感兴趣。2012年，Hagan博士加入了神经外科系，担任助理教授。

教育

研究生院
匹兹堡大学，宾夕法尼亚州匹兹堡（分子，细胞和发育生物学）

beplay苹果手机能用吗研究信息

我的研beplay苹果手机能用吗究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

最近的出版物（自2004年以来）

  1. Cui, X., Zhang, Y., Yang, J., Sun, X.,哈根，J.P。，Guha，S。和Li，M。（2014）ZIP4赋予对锌缺乏诱导的胰腺癌凋亡的抗性。细胞Cycle13(7): 1180-1196PMCID: PMC4013168
  2. Zhang，Y.，Yang，J.，Cui，X.，Chen，Y.，Zhu，V.F.，哈根，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 Medicine5：1322-1334PMCID: PMC3799489
  3. Shinoda, G., Shyh-Chang, N., de Soysa, T.Y., Zhu, H., Seligson, M.T., Shah, S.P., Abo-Sido, N., Yabuuchi, A.,哈根，J.P。，格雷戈里（R.I.（2013）LIN28的胎儿缺乏计划生长和葡萄糖代谢的终生畸变。Stem Cells31：1563-1573PMCID: PMC3775935
  4. Chen，L.，Zhang，Y.，Yang，J.，J.，哈根，J.P。, and Li, M. (2013) Vertebrate Animal Models of Glioma: Understanding the Mechanisms and Developing New Therapies.Biochimica et Biophysica Acta-Reviews on Cancerdoi: 10.1016/j.bbcan.2013.04.003PMCID: PMC372903
  5. Shinoda, G., de Soysa, T.Y., Seligson, M.T., Yabuuchi, A., Fujiwara, Y., Huang, P.Y.,哈根，J.P。，Gregory，R.I.，Moss，例如，G.Q。Daley（2013）LIN28A调节生殖细胞池的大小和生育能力。Stem Cells31:1001-1009PMCID: 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.细胞生理学杂志228：1377-1382PMID: 23254685
  7. Chang, H.M., Martinez, N.J., Thornton, J.E.,哈根，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 Communications3: 923PMCID: 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.细胞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，J.M，哈根，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.细胞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.Blood118: 6132-6140PMCID: PMC3234669
  11. Wenzel，P.L.，Chong，J.L.，Saenz-Robles，M.T.，Ferrey，A.，哈根，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 Biology351: 35-45.PMCID：PMC3868453
  12. Santanam, U., Zanesi, N., Efanov, A., Costinean, S., Palamarchuk, A.,哈根，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 USA107：12210-12215。PMCID：PMC2901490
  13. Liu, J.Q., Joshi, P.S., Wang, C., El-Omrani, H.Y., Xiao, Y., Liu, X.P.,哈根，J.P。，Liu，C.G.，Wu，L.C。和Bai，X.F.（2010年）靶向激活诱导的胞苷脱氨酶克服CTL对免疫疗法的肿瘤逃避。免疫学杂志184：5435-5443。PMCID: PMC2874093
  14. 哈根，J.P。#, Piskounova, E.#, and Gregory, R.I. (2009) Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells.自然结构和分子生物学16: 1021-1025.PMCID: PMC2758923
  15. Northcott, P.A.#, Fernandez-L, A.#,哈根，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 Research69：3249-3255。PMCID：PMC2836891
  16. 哈根，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 One4: 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.（2009）靶向含WW结构域的氧化还原酶肿瘤抑制剂的消融导致类固醇生成受损。Endocrinology150: 1530-1535.PMCID: PMC2654736
  18. Resnick, K.E., Alder, H.,哈根，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.妇科肿瘤学112: 55-59.PMID: 18954897
  19. Chong, J.L., Wenzel, P.L., Saenz-Robles, M.T., Nair, V., Ferrey, A.,哈根，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.Nature462：934-1025。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 Research37：D41-48。PMCID: PMC2686429
  21. Pichiorri, F., Suh, S.S., Ladetto, M., Kuehl, M., Palumbo,T., Drandi, D., Taccioli, C., Zanesi, N., Alder, H.,哈根，J.P。，Munker，R.，Volinia，S.，Boccadoro，M.，Garzon，R.，Palumbo，A.，Aqeilan，R.I。和Croce，C.M。（2008）microRNA调节与多发性骨髓瘤发病机理相关的关键基因。Proceedings National Academy of Science USA105: 12885-12890.PMCID：PMC2529070
  22. Rao, Y, Lee, Y., Jarjoura, D., Ruppert, A.S., Hsu, J.C., and哈根，J.P。（2008）MicroRNA微阵列数据的归一化技术的比较。Statistical Applications in Genetics and Molecular Biology,7: Article 22.PMID：18673291
  23. Aqeilan, R.I., Hassan, M.Q., de Bruin, A.,哈根，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 Chemistry283: 21629-21639.PMCID: PMC2490770
  24. Schmid, T., Jansen, A.P., Baker, A.R., Hegamyer, G.,哈根，J.P。, and Colburn, N.H. (2008) Tumor suppressorPDCD4is targeted during tumor promotion.Cancer Research68：1254-1260。PMID: 18296647
  25. 哈根，J.P。和Croce, C.M. (2007) MicroRNAs in Carcinogenesis.细胞遗传学和基因组研究beplay苹果手机能用吗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 Chemistry282: 21873-21883.PMID：17535812Free Full Text
  27. aqeilan，r.i，哈根，J.P。, Aqeilan, H.A., Petrocca, F., Fong, L.Y., and Croce, C.M. (2007) Inactivation of the Wwox gene accelerates forestomach tumor progressionin vivo.Cancer Research67: 5606-5610.PMCID：PMC2621009
  28. Bloomston，M.，Frankel，W.L.，Petrocca，F.，Volinia，S.，Alder，H.，哈根，J.P。、刘C.G。,Bhatt, D, Taccioli, C, C, C.M. (2007) MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis.美国医学协会杂志297: 1901-1908.PMID: 18296647
  29. aqeilan，r.i，Trapasso, F., Hussain, S., Costinean, S., Pekarsky, Y.,哈根，J.P。，Zanesi，N.，Kaou，M.，Stein，G.S.，Lian，J.B。和Croce，C.M。（2007）靶向WWOX的缺失揭示了肿瘤抑制功能。Proceedings National Academy of Science USA104: 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.,哈根，J.P。, and Croce, C.M. (2006)Tcl1CLL中的表达受miR-29和miR-181的调节。Cancer Research66：11590-11593。PMID：17178851Free Full Text
  31. Roldo，C.，Missiaglia，E.，N。，哈根，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.临床肿瘤学杂志24：4677-4684。PMID: 16966691
  32. Palamarchuk, A., Zanesi, N., Aqeilan, R.I., Efanov, A., Maximov, V., Santanam, U.,哈根，J.P。, Croce, C.M., and Pekarsky, Y. (2006)Tal1transgenic expression reveals absence of B lymphocytes.Cancer Research66: 6014-6017.PMID: 16778172Free Full Text
  33. Fan, T.,哈根，J.P。, Kozlov, S.V., Stewart, C.L., and Muegge, K. (2005)LSH控制印迹的沉默Cdkn1c基因。Development132：635-644。PMID: 15647320Free Full Text
  34. 哈根，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和Cdkn1c.Genomics85: 835-843.PMID: 16778172