Chromatin remodelling through oncogenic STAT5 in Peripheral T Cell Leukaemia and Lymphoma

NETWORK CONTRIBUTION

STAT5 is hyperactivated in a variety of haematopoietic tumours, prominently in Peripheral T-Cell Leukaemia and Lymphoma (PTCL). Hyperactivation of STAT5 is caused either by overexpression of STAT5A or by a somatic gain-of-function mutation in STAT5B (STAT5BN642H), most frequently found in PTCL. Given the proposed interplay of STAT5 with epigenetic modulators, we hypothesize that high level of activated STAT5 (=pSTAT5Y694, pYSTAT5) form a disease-propagating epigenetic landscape. To study the influence of STAT5 on these oncogenic rearrangements, we have created two transgenic mouse models expressing high levels of pYSTAT5, cSTAT5AFlagHIGH and STAT5BN642H mice, and two control lines expressing physiological levels of STAT5A or STAT5B. The cSTAT5AFlagHIGH and STAT5BN642H mice develop a PTCL-like disease.

Our major goal is to understand the dose effects of STAT5 that lead to potential TF cooperativity and changes in chromatin accessibility.

Within the project part we aim to compare STAT5-dependent epigenomes and interactomes to gain insights into pYSTAT5-dependent chromatin structures that are specific for disease. We will analyze how STAT5 influences the chromatin landscape, (ii) to unravel how this influence is changed during malignant T-cell transformation and (iii) to identify critical cooperativity partners of STAT5 in neoplastic T cells to open novel therapeutic avenues.

CONTACT

Department of Biomedical Sciences, Institute of Animal Breeding and Genetics
University of Veterinary Medicine Vienna, Vetmeduni Vienna

A-1210 Vienna
Austria

Richard.Moriggl@vetmeduni.ac.at

PUBLICATIONS

SFB-F61 / F28 related publications - Group Moriggl

Dolznig*, H., Grebien*, F., Deiner*, E.M., Stangl, K., Kolbus, A., Habermann, B., Kerenyi, M.A., Kieslinger, M., Moriggl, R., Beug§, H. and Müllner§, E.W. (2006). *equal contribution §equal contribution and equal correspondence
Erythroid progenitor renewal versus differentiation: genetic evidence for cell autonomous, essential functions of EpoR, Stat5 and the GR.
Oncogene 25:2890-900. doi: 10.1038/sj.onc.1209308
Hoelbl, A., Kovacic, B., Kerenyi, M.A., Simma, O., Warsch, W., Cui, Y., Beug, H., Hennighausen, L., Moriggl, R. and Sexl, V. (2006).
Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation.
Blood 107:4898-906. doi: 10.1182/blood-2005-09-3596
Jechlinger, M., Sommer, A., Moriggl, R., Seither, P., Kraut, N., Capodiecci, P., Donovan, M., Cordon-Cardo, C., Beug, H. and Grunert, S. (2006).
Autocrine PDGFR signaling promotes mammary cancer metastasis.
J Clin Invest 116:1561-70. doi: 10.1172/JCI24652
Kovacic, B., Stoiber, D., Moriggl, R., Weisz, E., Ott, R. G., Kreibich, R., Levy, D.E., Beug, H., Freissmuth, M., and Sexl, V. (2006).
STAT1 acts as a tumor promoter for leukemia development.
Cancer Cell 10:77-87.
Engblom, D., Kornfeld, J.W., Schwake, L., Tronche, F., Reimann, A., Beug, H., Hennighausen, L., Moriggl*, R. and Schütz*, G. (2007). *equal contribution and equal correspondence
Direct glucocorticoid receptor-Stat5 interaction in hepatocytes controls body size and maturation-related gene expression.
Genes Dev 21:1157-62. doi: 10.1101/gad.426007
Harir, N., Pecquet, C., Kerenyi, M., Sonneck, K., Kovacic, B., Nyga, R., Brevet, M., Dhennin, I., Gouilleux-Gruart, V., Beug, H., Valent, P., Lassoued, K., Moriggl, R. and Gouilleux, F. (2007).
Constitutive activation of Stat5 promotes its cytoplasmic localization and association with PI3-kinase in myeloid leukemias.
Blood 109:1678-86. doi: http://dx.doi.org/10.1182/blood-2006-01-029918
Li, G., Wang, Z., Zhang, Y., Kang, Z., Haviernikova, E., Cui, Y., Hennighausen, L., Moriggl, R., Wang, D., Tse, W. and Bunting, K.D. (2007).
STAT5 requires the N-domain to maintain hematopoietic stem cell repopulating function and appropriate lymphoid-myeloid lineage output.
Exp Hematol 35:1684-94. doi: 10.1016/j.exphem.2007.08.026
Tsareva, S., Moriggl, R., Corvinus, F., Wiederanders, B., Schütz, A., Kovacic, B., Friedrich, K. (2007).
STAT3 activation promotes invasive growth of colon carcinomas through matrix metalloproteinase induction.
Neoplasia 9:279-91. doi: 10.1593/neo.06820
Tuckermann, J.P., Kleiman, A., Moriggl, R., Spanbroek, R., Neumann, A., Illing, A., Clausen, B.E., Stride, B., Forster, I., Habenicht, A.J., Reichardt, H.M., Tronche, F., Schmid, W. and Schutz, G. (2007).
Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy.
J Clin Invest 117:1381-90. doi: 10.1172/JCI28034
Yao, Z., Kanno, Y., Kerenyi, M., Stephens, G., Durant, L., Watford, W.T., Laurence, A., Robinson, G.W., Shevach, E.M., Moriggl, R., Hennighausen, L., Wu, C. and O'Shea, J.J. (2007).
Nonredundant roles for Stat5a/b in directly regulating Foxp3.
Blood 109:4368-75. doi: 10.1182/blood-2006-11-055756
Grebien, F., Kerenyi, M.A., Kovacic, B., Kolbe, T., Becker, V., Dolznig, H., Pfeffer, K., Klingmuller, U., Müller, M., Beug, H., Müllner*, E.W. and Moriggl*, R. (2008). *equal contribution and equal correspondence
Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2.
Blood 111:4511-22. doi: http://dx.doi.org/10.1182/blood-2007-07-102848
Kerenyi*, M.A., Grebien*, F., Gehart, H., Schifrer, M., Artaker, M., Kovacic, B., Beug, H., Moriggl, R. and Müllner, E.W. (2008). *equal contribution
Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1.
Blood 112:3878-88. doi: 10.1182/blood-2008-02-138339
Mayerhofer, M., Gleixner, K.V., Hoelbl, A., Florian, S., Hoermann, G., Aichberger, K.J., Bilban, M., Esterbauer, H., Krauth, M.T., Sperr, W.R., Longley, J.B., Kralovic, R., Moriggl, R., Zappulla, J., Liblau, R.S., Schwarzinger, I., Sexl, V., Sillaber, C. and Valent, P. (2008).
Unique effects of KIT D816V in BaF3 cells: induction of cluster formation, histamine synthesis, and early mast cell differentiation antigens.
J Immunol 180:5466-76. doi: 10.4049/jimmunol.180.8.5466
Kornfeld, J.W., Grebien, F., Kerenyi, M.A., Friedbichler, K., Kovacic, B., Zankl, B., Hoelbl, A., Nivarti, H., Beug, H., Sexl, V., Müller, M., Kenner, L., Müllner, E.W., Gouilleux, F. and Moriggl, R. (2008).
The different functions of Stat5 and chromatin alteration through Stat5 proteins.
Front Biosci 13:6237-54. [review] doi: dx.doi.org/10.2741/3151
Harir, N., Boudot, C., Friedbichler, K., Sonneck, K., Kondo, R., Martin-Lanneree, S., Kenner, L., Kerenyi, M., Yahiaoui, S., Gouilleux-Gruart, V., Gondry, J., Benit, L., Dusanter-Fourt, I., Lassoued, K., Valent, P., Moriggl*, R. and Gouilleux* F. (2008). *equal contribution and equal correspondence
Oncogenic Kit controls neoplastic mast cell growth through a Stat5/PI3-kinase signaling cascade.
Blood 112:2463-73. doi: 10.1182/blood-2007-09-115477
Tsyrulnyk, A. and Moriggl, R. (2008).
A detailed protocol for bacterial artificial chromosome recombineering to study essential genes in stem cells.
Hematopoietic Stem Cell Protocols. Methods in Molecular BiologyTM, Humana Press. 430:269-293. [book chapter] doi: 10.1007/978-1-59745-182-6_19 Online ISBN: 978-1-59745-182-6
Ecker, A., Simma, O., Hoelbl, A., Kenner, L., Beug, H., Moriggl, R. and Sexl, V. (2009).
The dark and the bright side of Stat3: proto-oncogene and tumor-suppressor.
Front Biosci 14:2944-58. [review] doi: dx.doi.org/10.2741/3425
Friedbichler, K., Kerenyi, M.A., Müllner, E.W. and Moriggl, R. (2009).
Stat5 as hematopoietic gatekeeper and oncogene upon tyrosine kinase-induced transformation.
In JAK-STAT Pathways in Disease (Stephanou, A., Ed.). Landes Biosci, Austin, TX. pp. 131-150. [book chapter] ISBN-13: 978-1587063152
Baumgartner, C., Sonneck, K., Mayerhofer, M., Gleixner, K., Fritz, R., Cerny-Reiterer, S., Kerenyi, M., Kornfeld, J.W., Sillaber, C., Moriggl, R. and Valent, P. (2009).
Expression of activated STAT5 in neoplastic mast cells in systemic mastocytosis: subcellular distribution and role of the transforming oncoprotein KIT D816V.
American J Pathol 75(6):2416-29. doi: 10.2353/ajpath.2009.080953
Pflegerl, P., Vesely, P., Hantusch, B., Schlederer, M., Zenz, R., Janig, E., Steiner, G., Meixner, A., Petzelbauer, P., Wolf, P., Soleiman, A., Egger, G., Moriggl, R., Kishimoto, T., Wagner, E.F., and Kenner, L. (2009).
Epidermal loss of JunB leads to a SLE phenotype due to hyper IL-6 signaling.
Proc Natl Acad Sci USA 106: 20423-20428. doi: 10.1073/pnas.0910371106
Blaas*, L., Kornfeld*, J.W., Schramek, D., Musteanu, M., Zollner, G., Gumhold, J., van Zijl, F., Schneller, D., Esterbauer, H., Egger, G., Mair, M., Kenner, L., Mikulits, W., Eferl, R., Moriggl, R., Penninger, J., Trauner, M., and Casanova, E. (2010). *equal contribution
Disruption of the growth hormone--signal transducer and activator of transcription 5--insulinlike growth factor 1 axis severely aggravates liver fibrosis in a mouse model of cholestasis.
Hepatology 51: 1319-1326. doi: 10.1002/hep.23469
Friedbichler, K., Kerenyi, M.A., Kovacic, B., Li, G., Hoelbl, A., Yahiaoui, S., Sexl, V., Mullner§, E.W., Fajmann, S., Cerny-Reiterer, S., Valent, P., Beug†, H., Gouilleux, F., Bunting, K.D., and Moriggl, R. (2010). §SFB member of the 1st funding period †1945-2011, SFB member of the 1st funding period; associated with coordination project
Stat5a serine 725 and 779 phosphorylation is a prerequisite for hematopoietic transformation.
Blood 116: 1548-1558. doi: 10.1182/blood-2009-12-258913
Hoelbl*, A., Schuster*, C., Kovacic, B., Zhu, B., Wickre, M., Hoelzl, M.A., Fajmann, S., Grebien, F., Warsch, W., Stengl, G., Hennighausen, L., Poli, V., Beug†, H., Moriggl, R., and Sexl, V. (2010). *equal contribution †1945-2011, SFB member of the 1st funding period; associated with coordination project
Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia.
EMBO Mol Med 2: 98-110. doi: 10.1002/emmm.201000062
Li, G., Miskimen, K.L., Wang, Z., Xie, X.Y., Brenzovich, J., Ryan, J.J., Tse, W., Moriggl, R., and Bunting, K.D. (2010).
STAT5 requires the N-domain for suppression of miR15/16, induction of bcl-2, and survival signaling in myeloproliferative disease.
Blood 115: 1416-1424. doi: 10.1182/blood-2009-07-234963
Creamer, B.A., Sakamoto, K., Schmidt, J.W., Triplett, A.A., Moriggl, R., and Wagner, K.U. (2010).
Stat5 promotes survival of mammary epithelial cells through transcriptional activation of a distinct promoter in Akt1.
Mol Cell Biol 30: 2957-2970. doi: 10.1128/MCB.00851-09
Li, G., Miskimen, K.L., Wang, Z., Xie, X.Y., Tse, W., Gouilleux, F., Moriggl, R., and Bunting, K.D. (2010).
Effective targeting of STAT5-mediated survival in myeloproliferative neoplasms using ABT-737 combined with rapamycin.
Leukemia 24: 1397-1405. doi: 10.1038/leu.2010.131
Kornfeld, J.W., Isaacs, A., Vitart, V., Pospisilik, J.A., Meitinger, T., Gyllensten, U., Wilson, J.F., Rudan, I., Campbell, H., Penninger, J.M., Sexl, V., Moriggl, R., van Duijn, C., Pramstaller, P.P., and Hicks, A.A. (2011).
Variants in STAT5B Associate with Serum TC and LDL-C Levels.
J Clin Endocrinol Metab. 96: E1496-501. doi: dx.doi.org/10.1210/jc.2011-0322
Mueller, K.M., Kornfeld, J.W., Friedbichler, K., Blaas, L., Egger, G., Esterbauer, H., Hasselblatt, P., Schlederer, M., Haindl, S., Wagner, K.U., Engblom, D., Haemmerle, G., Kratky, D., Sexl, V., Kenner, L., Kozlov, A.V., Terracciano, L., Zechner, R., Schuetz, G., Casanova, E., Pospisilik, J.A., Heim, M.H., and Moriggl, R. (2011).
Impairment of hepatic growth hormone and glucocorticoid receptor signaling causes steatosis and hepatocellular carcinoma in mice.
Hepatology 54: 1398-1409. doi: 10.1002/hep.24509
Schneller*, D., Machat*, G., Sousek*, A., Proell, V., van Zijl, F., Zulehner, G., Huber, H., Mair, M., Muellner, M.K., Nijman, S.M., Eferl, R., Moriggl, R., and Mikulits, W. (2011). *equal contribution
p19(ARF) /p14(ARF) controls oncogenic functions of Stat3 in hepatocellular carcinoma.
Hepatology 54: 164-172. doi: 10.1002/hep.24329

Warsch, W., Kollmann, K., Eckelhart, E., Fajmann, S., Cerny-Reiterer, S., Holbl, A., Gleixner, K.V., Dworzak, M., Mayerhofer, M., Hoermann, G., Herrmann, H., Sillaber, C., Egger, G., Valent, P., Moriggl, R., and Sexl, V. (2011).
High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia.
Blood 117: 3409-3420. doi: http://dx.doi.org/10.1182/blood-2009-10-248211
Friedbichler, K., Hoelbl, A., Li, G., Bunting, K.D., Sexl, V., Gouilleux, F., and Moriggl, R. (2011).
Serine phosphorylation of the Stat5a C-terminus is a driving force for transformation.
Front Biosci 17: 3043-3056. [review] doi: http://dx.doi.org/10.2741/3897
Ermakova, O., Piszczek, L., Luciani, L., Cavalli, F.M., Ferreira, T., Farley, D., Rizzo, S., Paolicelli, R.C., Al-Banchaabouchi, M., Nerlov, C., Moriggl, R., Luscombe, N.M., and Gross, C. (2011).
Sensitized phenotypic screening identifies gene dosage sensitive region on chromosome 11 that predisposes to disease in mice.
EMBO Mol Med 3: 50-66. doi: 10.1002/emmm.201000112
Ferbeyre, G., and Moriggl, R. (2011).
The role of Stat5 transcription factors as tumor suppressors or oncogenes.
Biochim Biophys Acta 1815: 104-114. [review] doi: 10.1016/j.bbcan.2010.10.004
Laimer, D., Dolznig, H., Kollmann, K., Vesely, P.W., Schlederer, M., Merkel, O., Schiefer, A.-I., Hassler, M.R., Heider, S., Amenitsch, L., Thallinger, C., Staber, P.B., Simonitsch-Klupp, I., Artaker, M., Lagger, S., Pileri, S., Piccaluga, P.P., Valent, P., Messana, K., Landra, I., Weichhart, T., Knapp, S., Shehata, M., Todaro, M., Sexl, V., Höfler, G., Piva, R., Medico, E., Riggeri, B.A., Cheng, M., Eferl, R., Egger, G., Penninger, J.M., Jaeger, U., Moriggl, R., Inghirami, G., and Kenner, L. (2012).
PDGFR blockade is a rational and effective therapy for NPM-ALK–driven lymphomas.
Nat Med 18: 1699-1704. doi: 10.1038/nm.2966
Warsch, W., Grundschober, E., Berger, A., Gille, L., Cerny-Reiterer, S., Tigan, A.-S., Hoelbl-Kovacic, A., Valent, P., Moriggl, R., and Sexl, V. (2012).
STAT5 triggers BCR-ABL1 mutation by mediating ROS production in chronic myeloid leukaemia.
Oncotarget 3: 1669-1687. online ISSN: 1949-2553
Friedbichler, K., Themanns, M., Mueller, K.M., Schlederer, M., Kornfeld, J.-W., Terracciano, L.M., Kozlov, A.V., Haindl, S., Kenner, L., Kolbe, T., Mueller, M., Snibson, K., Heim, M.H., and Moriggl, R. (2012).
Growth hormone-induced STAT5 signaling causes gigantism, inflammation and premature death but protects mice from aggressive liver cancer.
Hepatology 55: 941-952. doi: 10.1002/hep.24765
Kovacic, B., Hoelbl, A., Litos, G., Alacakaptan, M., Schuster, C., Fischhuber, K.M., Kerenyi, M.A., Stengl, G., Moriggl, R., Sexl, V., and Beug†, H. (2012). †1945-2011, SFB member of the 1st funding period; associated with coordination project
Diverging fates of cells of origin in acute and chronic leukaemia.
EMBO Mol Med 4: 283-297. doi: 10.1002/emmm.201100208
Musteanu, M., Blaas, L., Zenz, R., Svinka, J., Hoffmann, T., Grabner, B., Schramek, D., Kantner, H.P., Müller, M., Kolbe, T., Rülicke, T., Moriggl, R., Kenner, L., Stoiber, D., Penninger, J., Popper, H., Casanova, E., and Eferl, R. (2012).
A mouse model to identify cooperating signaling pathways in cancer.
Nat Methods 9: 897-900. doi: 10.1038/nmeth.2130
Nivarthi, H., Friedbichler, K., and Moriggl, R. (2012).
Stat5 as a Hematopoietic Master Regulator for Differentiation and Neoplasia Development.
In Jak-Stat Signaling: From Basics to Disease. (Decker, T. and Müller, M., Eds.) Springer Wien Heidelberg New York Dordrecht London. pp. 153-168. [book chapter] doi: 10.1007/978-3-7091-0891-8_10 ISBN: 978-3-7091-0890-1
Mueller, K.M., Themanns, M., Friedbichler, K., Kornfeld, J.W., Esterbauer, H., Tuckermann, J.P., and Moriggl, R. (2012).
Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development.
Mol Cell Endocrinol 361: 1-11. [review] doi: 10.1016/j.mce.2012.03.026
Kollmann, K., Heller, G., Schneckenleitner, C., Warsch, W., Scheicher, R., Ott, R.G., Schäfer, M., Fajmann, S., Schlederer, M., Schiefer, A.-I., Reichart, U., Mayerhofer, M., Hoeller, C., Zöchbauer-Müller, S., Kerjaschki, D., Bock, C., LKenner, L., Hoefler, G., Freissmuth, M., Green, A.R., Moriggl, R., Busslinger, M., Malumbres, M., and Sexl, V. (2013).
A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.
Cancer Cell 24: 167-181. doi: dx.doi.org/10.1016/j.ccr.2013.07.012
Chatain, N., Ziegler, P., Fahrenkamp, D., Jost, E., Moriggl, R., Schmitz-Van de Leur, H., and Müller-Newen, G. (2013).
Scr family kinases mediate cytoplasmic retention of activated STAT5 in BCR-ABL-positive cells.
Oncogene 32: 3587-3597. doi: 10.1038/onc.2012.369
Gordziel, C., Bratsch, J., Moriggl, R., Knosel, T. and Friedrich. K. (2013).
Both STAT1 and STAT3 are favourable prognostic determinants in colorectal carcinoma.
Br J Cancer 109: 138-146. doi: 10.1038/bjc.2013.274
McGuckin, C.P., Jurga, M., Miller, A.M., Sarnowska, A., Wiedner, M., Boyle, N.T., Lynch, M.A., Jablonska, A., Drela, K., Lukomska, B., Domanska-Janik, K., Kenner, L., Moriggl, R., Degoul, O., Perruisseau-Carrier, C., and Forraz, N. (2013).
Ischemic brain injury: a consortium analysis of key factors involved in mesenchymal stem cell-mediated inflammatory reduction.
Arch Biochem Biophys. 534: 88-97. doi: 10.1016/j.abb.2013.02.005
Berger*, A., Hoelbl-Kovacic*, A., Bourgeais, J., Hoefling, L., Warsch, W., Grundschober, E., Uras, I.Z., Menzl, I., Putz, E.M., Hoermann, G., Schuster, C., Fajmann, S., Leitner, E., Kubicek, S., Moriggl, R., Gouilleux, F., and Sexl, V. (2014). *equal contribution
PAK-dependent STAT5 serine phosphorylation is required for BCR-ABL-induced leukemogenesis.
Leukemia 28: 629-641. doi: 10.1038/leu.2013.351
Berger, A., Sexl, V., Valent, P., and Moriggl, R. (2014).
Inhibition of STAT5: A therapeutic option in BCR-ABL1-driven leukemia.
Oncotarget 5: 9564-9576. Online ISSN: 1949-2553
Strobl, B., and Moriggl, R. (2014).
Editorial: Recovery from chemotherapy depends on STAT1 for replenishment of B lymphopoiesis.
J Leukocyte Biol 95: 849-851. [editorial review] doi: 10.1189/jlb.0114051
Schlederer, M., Mueller, K.M., Haybaeck, J., Heider, S., Huttary, N., Rosner, M., Hengstschlager, M., Moriggl, R., Dolznig, H., and Kenner, L. (2014).
Reliable Quantification of Protein Expression and Cellular Localization in Histological Sections.
PLoS One 9: e100822. doi: 10.1371/journal.pone.0100822
Bibi, S., Arslanhan, M.D., Langenfeld, F., Jeanningros, S., Cerny-Reiterer, S., Hadzijusufovic, E., Tchertanov, L., Moriggl, R., Valent, P., and Arock, M. (2014).
Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy.
Haematologica 99: 417-429. [review] doi: 10.3324/haematol.2013.098442
Gilbert*, S., Nivarthi*, H., Mayhew*, C.N., Lo, Y.H., Noah, T.K., Vallance, J., Rulicke, T., Müller, M., Jegga, A.G., Tang, W., Zhang, D., Helmrath, M., Shroyer, N., Moriggl, R., and Han, X. (2015). *equal contribution
Activated STAT5 Confers Resistance to Intestinal Injury by Increasing Intestinal Stem Cell Proliferation and Regeneration.
Stem Cell Rep 4: 209-225. doi: 10.1016/j.stemcr.2014.12.004
Nivarthi, H., Prchal-Murphy, M., Swoboda, A., Hager, M., Schlederer, M., Kenner, L., Tuckermann, J., Sexl, V., Moriggl, R., and Ermakova, O. (2015).
Stat5 gene dosage in T cells modulates CD8 T cell homeostasis and attenuates contact hypersensitivity response in mice.
Allergy 70: 67-79. doi: 10.1111/all.12535
Pencik, J., Schlederer, M., Gruber, W., Unger, C., Walker, S.M., Chalaris, A., Marié, I.J., Hassler, M.R., Javaheri, T., Aksoy, O., Blayney, J.K., Prutsch, N., Skucha, A., Herac, M., Krämer, O.H., Mazal, P., Grebien, F., Egger, G., Poli, V., Mikulits§, W., Eferl§, R., Esterbauer, H., Kennedy, R., Fend, F., Scharpf, M., Braun, M., Perner, S., Levy, D.E., Malcolm, T., Turner, S.D., Haitel, A., Susani, M., Moazzami, A., Rose-John, S., Aberger, F., Merkel, O., Moriggl, R., Culig, Z., Dolznig, H., and Kenner, L. (2015). §SFB member of the 1st and 2nd funding period
STAT3 regulated ARF expression suppresses prostate cancer metastasis.
Nat Commun. 6:7736. doi: 10.1038/ncomms8736
Schutz, A., Roser, K., Klitzsch, J., Lieder, F., Aberger, F., Gruber, W., Mueller, K.M., Pupyshev, A., Moriggl, R., and Friedrich, K. (2015).
Lung Adenocarcinomas and Lung Cancer Cell Lines Show Association of MMP-1 Expression With STAT3 Activation.
Transl Oncol 8: 97-105. doi: dx.doi.org/10.1016/j.tranon.2015.02.002
Girardot, M., Pecquet, C., Chachoua, I., Van Hees, J., Guibert, S., Ferrant, A., Knoops, L., Baxter, E.J., Beer, P.A., Giraudier, S., Moriggl, R., Vainchenker, W., Green, A.R., and Constantinescu, S.N. (2015).
Persistent STAT5 activation in myeloid neoplasms recruits p53 into gene regulation.
Oncogene 34:1323-1332. doi: 10.1038/onc.2014.60
Merkel, O., Hamacher, F., Griessl, R., Grabner, L., Schiefer, A.I., Prutsch, N., Baer, C., Egger, G., Schlederer, M., William Krenn, P., Nicole Hartmann, T., Simonitsch-Klupp, I., Plass, C., Staber, P., Moriggl, R., Turner, S.D., Greil, R., and Kenner, L. (2015).
Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation.
J Pathol Mar 26. [Epub ahead of print] doi: 10.1002/path.4539
Park, J., Schlederer, M., Schreiber, M., Ice, R., Merkel, O., Bilban, M., Hofbauer, S., Kim, S., Addison, J., Zou, J., Ji, C., Bunting, S.T., Wang, Z., Shoham, M., Huang, G., Bago-Horvath, Z., Gibson, L.F., Rojanasakul, Y., Remick, S., Ivanov, A., Pugacheva, E., Bunting, K.D., Moriggl, R., Kenner, L., and Tse, W. (2015).
AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.
Oncotarget. Online ISSN: 1949-2553
Minas, T.Z., Han, J., Javaheri, T., Hong, S.H., Schlederer, M., Saygideger-Kont, Y., Celik, H., Mueller, K.M., Temel, I., Ozdemirli, M., Kovar, H., Erkizan, H.V., Toretsky, J., Kenner, L., Moriggl, R., and Uren, A. (2015).
YK-4-279 effectively antagonizes EWS-FLI1 induced leukemia in a transgenic mouse model.
Oncotarget 6, 37678-37694
Bourgeais, J., Ishac, N., Medrzycki, M., Brachet-Botineau, M., Desbourdes, L., Gouilleux-Gruart, V., Pecnard, E., Rouleux-Bonnin, F., Gyan, E., Domenech, J., Mazurier, F., Moriggl, R., Bunting, K.D., Herault, O., and Gouilleux, F. (2016).
Oncogenic STAT5 signaling promotes oxidative stress in chronic myeloid leukemia cells by repressing antioxidant defenses.
Oncotarget 10.18632/oncotarget.11480
Javaheri, T., Kazemi, Z., Pencik, J., Pham, H.T., Kauer, M., Noorizadeh, R., Sax, B., Nivarthi, H., Schlederer, M., Maurer, B., Hofbauer, M., Aryee, D.N., Wiedner, M., Tomazou, E.M., Logan, M., Hartmann, C., Tuckermann, J.P., Kenner, L., Mikula, M., Dolznig, H., Uren, A., Richter, G.H., Grebien, F., Kovar, H., and Moriggl, R. (2016).
Increased survival and cell cycle progression pathways are required for EWS/FLI1-induced malignant transformation.
Cell Death Dis 7, e2419
Nivarthi, H., Gordziel, C., Themanns, M., Kramer, N., Eberl, M., Rabe, B., Schlederer, M., Rose-John, S., Knosel, T., Kenner, L., Freund, P., Aberger, F., Han, X., Kralovics, R., Dolznig, H., Jennek, S., Friedrich, K., and Moriggl, R. (2016).
The ratio of STAT1 to STAT3 expression is a determinant of colorectal cancer growth.
Oncotarget 10.18632/oncotarget.9315
Park, J., Kim, S., Joh, J., Remick, S.C., Miller, D.M., Yan, J., Kanaan, Z., Chao, J.H., Krem, M.M., Basu, S.K., Hagiwara, S., Kenner, L., Moriggl, R., Bunting, K.D., and Tse, W. (2016).
MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling.
Oncotarget 10.18632/oncotarget.9759
Pencik, J., Pham, H.T., Schmoellerl, J., Javaheri, T., Schlederer, M., Culig, Z., Merkel, O., Moriggl, R., Grebien, F., and Kenner, L. (2016).
JAK-STAT signaling in cancer: From cytokines to non-coding genome.
Cytokine 10.1016/j.cyto.2016.06.017
Themanns, M., Mueller, K.M., Kessler, S.M., Golob-Schwarzl, N., Mohr, T., Kaltenecker, D., Bourgeais, J., Paier-Pourani, J., Friedbichler, K., Schneller, D., Schlederer, M., Zebedin-Brandl, E., Terracciano, L.M., Han, X., Kenner, L., Wagner, K.U., Mikulits, W., Kozlov, A.V., Heim, M.H., Gouilleux, F., Haybaeck, J., and Moriggl, R. (2016).
Hepatic Deletion of Janus Kinase 2 Counteracts Oxidative Stress in Mice.
Sci Rep 6, 34719
Boidol, B., Kornauth, C., van der Kouwe, E., Prutsch, N., Kazianka, L., Gultekin, S., Hoermann, G., Mayerhoefer, M.E., Hopfinger, G., Hauswirth, A., Panny, M., Aretin, M.B., Hilgarth, B., Sperr, W.R., Valent, P., Simonitsch-Klupp, I., Moriggl, R., Merkel, O., Kenner, L., Jager, U., Kubicek, S., and Staber, P.B. (2017).
First in human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia.
Blood 10.1182/blood-2017-05-785683
Fragiadaki, M., Lannoy, M., Themanns, M., Maurer, B., Leonhard, W.N., Peters, D.J., Moriggl, R., and Ong, A.C. (2017).
STAT5 drives abnormal proliferation in autosomal dominant polycystic kidney disease.
Kidney Int 10.1016/j.kint.2016.10.039
Freund, P., Kerenyi, M.A., Hager, M., Wagner, T., Wingelhofer, B., Pham, H.T., Elabd, M., Han, X., Valent, P., Gouilleux, F., Sexl, V., Kramer, O.H., Groner, B., and Moriggl, R. (2017).
O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies.
Leukemia 10.1038/leu.2017.4
Friedrich, K., Dolznig, H., Han, X., and Moriggl, R. (2017).
Steering of carcinoma progression by the YIN/YANG interaction of STAT1/STAT3.
Biosci Trends 10.5582/bst.2016.01250
Ghanem, S., Friedbichler, K., Boudot, C., Bourgeais, J., Gouilleux-Gruart, V., Regnier, A., Herault, O., Moriggl, R., and Gouilleux, F. (2017).
STAT5A/5B-specific expansion and transformation of hematopoietic stem cells.
Blood Cancer J 7, e514
Kaltenecker, D., Mueller, K.M., Benedikt, P., Feiler, U., Themanns, M., Schlederer, M., Kenner, L., Schweiger, M., Haemmerle, G., and Moriggl, R. (2017).
Adipocyte STAT5 deficiency promotes adiposity and impairs lipid mobilisation in mice.
Diabetologia 60, 296-305
Keller, A., Wingelhofer, B., Peter, B., Bauer, K., Berger, D., Gamperl, S., Reifinger, M., Cerny-Reiterer, S., Moriggl, R., Willmann, M., Valent, P., and Hadzijusufovic, E. (2017).
The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma.
Vet Comp Oncol 10.1111/vco.12311
Mueller, K.M., Hartmann, K., Kaltenecker, D., Vettorazzi, S., Bauer, M., Mauser, L., Amann, S., Jall, S., Fischer, K., Esterbauer, H., Muller, T.D., Tschop, M.H., Magnes, C., Haybaeck, J., Scherer, T., Bordag, N., Tuckermann, J.P., and Moriggl, R. (2017).
Adipocyte Glucocorticoid Receptor Deficiency Attenuates Aging- and Hfd-Induced Obesity, and Impairs the Feeding-Fasting Transition.
Diabetes 66, 272-286
Orlova, A., Wingelhofer, B., Neubauer, H.A., Maurer, B., Berger-Becvar, A., Keseru, G.M., Gunning, P.T., Valent, P., and Moriggl, R. (2018).
Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas.
Expert Opin Ther Targets 22, 45-57. doi: 10.1080/14728222.2018.1406924
Schrader, A., Crispatzu, G., Oberbeck, S., Mayer, P., Putzer, S., von Jan, J., Vasyutina, E., Warner, K., Weit, N., Pflug, N., Braun, T., Andersson, E.I., Yadav, B., Riabinska, A., Maurer, B., Ventura Ferreira, M.S., Beier, F., Altmuller, J., Lanasa, M., Herling, C.D., Haferlach, T., Stilgenbauer, S., Hopfinger, G., Peifer, M., Brummendorf, T.H., Nurnberg, P., Elenitoba-Johnson, K.S.J., Zha, S., Hallek, M., Moriggl, R., Reinhardt, H.C., Stern, M.H., Mustjoki, S., Newrzela, S., Frommolt, P., and Herling, M. (2018).
Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL.
Nat Commun 9, 697
Wingelhofer, B., Maurer, B., Heyes, E.C., Cumaraswamy, A.A., Berger-Becvar, A., de Araujo, E.D., Orlova, A., Freund, P., Ruge, F., Park, J., Tin, G., Ahmar, S., Lardeau, C.H., Sadovnik, I., Bajusz, D., Keseru, G.M., Grebien, F., Kubicek, S., Valent, P., Gunning, P.T., and Moriggl, R. (2018).
Pharmacologic inhibition of STAT5 in acute myeloid leukemia.
Leukemia 10.1038/s41375-017-0005-9

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