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


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.

Heidi is interested in how mutated STAT5 alters the chromatin landscape of different T-cell subsets, driving oncogenic transformation and progression in specific T-cell lymphoma entities. To this end, she is studying disease mechanisms of oncogenic STAT5, highlighting common and unique downstream effectors in specific disease subtypes, which may assist with identifying new targeted therapies for T-cell lymphoma patients.


SFB-F61 / F28 related publications - Groups Neubauer and Moriggl

Abdeldayem, A., Raouf, Y. S., Constantinescu, S. N., Moriggl, R. and Gunning, P. T.
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Cancers (Basel). 2020 Apr 21;12(4). pii: cancers12041021. doi: 10.3390/cancers12041021
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The neonatal microenvironment programs innate gammadelta T cells through the transcription factor STAT5
J Clin Invest. 2020 Apr 13. pii: 131241. doi: 10.1172/JCI131241
Maurer, B., Nivarthi, H., Wingelhofer, B., Pham, H. T. T., Schlederer, M., Suske, T., Grausenburger, R., Schiefer, A. I., Prchal-Murphy, M., Chen, D., Winkler, S., Merkel, O., Kornauth, C., Hofbauer, M., Hochgatterer, B., Hoermann, G., Hoelbl-Kovacic, A., Prochazkova, J., Lobello, C., Cumaraswamy, A. A., Latzka, J., Kitzwogerer, M., Chott, A., Janikova, A., Pospisilova, S., Loizou, J. I., Kubicek, S., Valent, P., Kolbe, T., Grebien, F., Kenner, L., Gunning, P. T., Kralovics, R., Herling, M., Muller, M., Rulicke, T., Sexl, V. and Moriggl, R.
High activation of STAT5A drives peripheral T-cell lymphoma and leukemia
Haematologica. 2019 May 23. pii: haematol.2019.216986. doi: 10.3324/haematol.2019.216986
Schmoellerl, J., Barbosa, I. A. M., Eder, T., Brandstoetter, T., Schmidt, L., Maurer, B., Troester, S., Pham, H. T. T., Sagarajit, M., Ebner, J., Manhart, G., Aslan, E., Terlecki-Zaniewicz, S., Van der Veen, C., Hoermann, G., Duployez, N., Petit, A., Lapillonne, H., Puissant, A., Itzykson, R. A., Moriggl, R. H., Heuser, M., Meisel, R., Valent, P., Sexl, V., Zuber, J. and Grebien, F.
CDK6 is an essential direct target of NUP98-fusion proteins in acute myeloid leukemia
Blood. 2020 Apr 28. pii: 454667. doi: 10.1182/blood.2019003267
Unterleuthner, D., Neuhold, P., Schwarz, K., Janker, L., Neuditschko, B., Nivarthi, H., Crncec, I., Kramer, N., Unger, C., Hengstschlager, M., Eferl, R., Moriggl, R., Sommergruber, W., Gerner, C. and Dolznig, H.
Cancer-associated fibroblast-derived WNT2 increases tumor angiogenesis in colon cancer
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de Araujo, E. D., Orlova, A., Neubauer, H. A., Bajusz, D., Seo, H. S., Dhe-Paganon, S., Keseru, G. M., Moriggl, R. and Gunning, P. T.
Structural Implications of STAT3 and STAT5 SH2 Domain Mutations
Cancers (Basel). 2019 Nov 8;11(11). pii: cancers11111757. doi: 10.3390/cancers11111757
Kaltenecker, D., Themanns, M., Mueller, K.M., Spirk, K., Suske, T., Merkel, O., Kenner, L., Luís, A., Kozlov, A., Haybaeck, J., Müller, M., Han, X. and Moriggl, R.
Hepatic growth hormone - JAK2 - STAT5 signalling: Metabolic function, non-alcoholic fatty liver disease and hepatocellular carcinoma progression
Cytokine 2019 Oct 30;124:154569. doi: 10.1016/j.cyto.2018.10.010
Orlova, A., Wagner, C., de Araujo, E. D., Bajusz, D., Neubauer, H. A., Herling, M., Gunning, P. T., Keseru, G. M. and Moriggl, R.
Direct Targeting Options for STAT3 and STAT5 in Cancer
Cancers (Basel). 2019 Dec 3;11(12). pii: cancers11121930. doi: 10.3390/cancers11121930
Klein, K., Witalisz-Siepracka, A., Maurer, B., Prinz, D., Heller, G., Leidenfrost, N., Prchal-Murphy, M., Suske, T., Moriggl, R. and Sexl, V.
STAT5B(N642H) drives transformation of NKT cells: a novel mouse model for CD56(+) T-LGL leukemia
Leukemia. 2019 Apr 9. pii: 10.1038/s41375-019-0471-3. doi: 10.1038/s41375-019-0471-3
Orlova, A., Neubauer, H. A. and Moriggl, R.
The stromal microenvironment provides an escape route from FLT3 inhibitors through the GAS6-AXL-STAT5 axis
Haematologica. 2019 Oct;104(10):1907-1909. doi: 10.3324/haematol.2019.225862
Prutsch, N., Gurnhofer, E., Suske, T., Liang, H. C., Schlederer, M., Roos, S., Wu, L. C., Simonitsch-Klupp, I., Alvarez-Hernandez, A., Kornauth, C., Leone, D. A., Svinka, J., Eferl, R., Limberger, T., Aufinger, A., Shirsath, N., Wolf, P., Hielscher, T., Aberger, F., Schmoellerl, J., Stoiber, D., Strobl, B., Jager, U., Staber, P. B., Grebien, F., Moriggl, R., Muller, M., Inghirami, G. G., Sanda, T., Look, A. T., Turner, S. D., Kenner, L. and Merkel, O.
Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma
Leukemia. 2018 Aug 21. pii: 10.1038/s41375-018-0239-1. doi: 10.1038/s41375-018-0239-1
Boutillon, F., Pigat, N., Sala, L. S., Reyes-Gomez, E., Moriggl, R., Guidotti, J. E. and Goffin, V.
STAT5a/b Deficiency Delays, but does not Prevent, Prolactin-Driven Prostate Tumorigenesis in Mice
Cancers (Basel). 2019 Jul 2;11(7). pii: cancers11070929. doi: 10.3390/cancers11070929
Aigner, P., Mizutani, T., Horvath, J., Eder, T., Heber, S., Lind, K., Just, V., Moll, H. P., Yeroslaviz, A., Fischer, M. J. M., Kenner, L., Gyorffy, B., Sill, H., Grebien, F., Moriggl, R., Casanova, E. and Stoiber, D.
STAT3beta is a tumor suppressor in acute myeloid leukemia
Blood Adv. 2019 Jul 9;3(13):1989-2002. doi: 10.1182/bloodadvances.2018026385
Maurer, B., Nivarthi, H., Wingelhofer, B., Pham, H. T. T., Schlederer, M., Suske, T., Grausenburger, R., Schiefer, A. I., Prchal-Murphy, M., Chen, D., Winkler, S., Merkel, O., Kornauth, C., Hofbauer, M., Hochgatterer, B., Hoermann, G., Hoelbl-Kovacic, A., Prochazkova, J., Lobello, C., Cumaraswamy, A. A., Latzka, J., Kitzwogerer, M., Chott, A., Janikova, A., Pospisilova, S., Loizou, J. I., Kubicek, S., Valent, P., Kolbe, T., Grebien, F., Kenner, L., Gunning, P. T., Kralovics, R., Herling, M., Muller, M., Rulicke, T., Sexl, V. and Moriggl, R.
High activation of STAT5A drives peripheral T-cell lymphoma and leukemia
Haematologica. 2019 May 23. pii: haematol.2019.216986. doi: 10.3324/haematol.2019.216986
de Araujo, E. D., Erdogan, F., Neubauer, H. A., Meneksedag-Erol, D., Manaswiyoungkul, P., Eram, M. S., Seo, H. S., Qadree, A. K., Israelian, J., Orlova, A., Suske, T., Pham, H. T. T., Boersma, A., Tangermann, S., Kenner, L., Rulicke, T., Dong, A., Ravichandran, M., Brown, P. J., Audette, G. F., Rauscher, S., Dhe-Paganon, S., Moriggl, R. and Gunning, P. T.
Structural and functional consequences of the STAT5B(N642H) driver mutation
Nat Commun. 2019 Jun 7;10(1):2517. doi: 10.1038/s41467-019-10422-7
Liu, R., Moriggl, R., Zhang, D., Li, H., Karns, R., Ruan, H. B., Niu, H., Mayhew, C., Watson, C., Bangar, H., Cha, S. W., Haslam, D., Zhang, T., Gilbert, S., Li, N., Helmrath, M., Wells, J., Denson, L. and Han, X.
Constitutive STAT5 activation regulates Paneth and Paneth-like cells to control Clostridium difficile colitis
Life Sci Alliance. 2019 Apr 4;2(2). pii: 2/2/e201900296. doi: 10.26508/lsa.201900296
Rauth, M., Freund, P., Orlova, A., Grunert, S., Tasic, N., Han, X., Ruan, H. B., Neubauer, H. A. and Moriggl, R.
Cell Metabolism Control Through O-GlcNAcylation of STAT5: A Full or Empty Fuel Tank Makes a Big Difference for Cancer Cell Growth and Survival
Int J Mol Sci. 2019 Feb 27;20(5). pii: ijms20051028. doi: 10.3390/ijms20051028
Kosack, L., Wingelhofer, B., Popa, A., Orlova, A., Agerer, B., Vilagos, B., Majek, P., Parapatics, K., Lercher, A., Ringler, A., Klughammer, J., Smyth, M., Khamina, K., Baazim, H., de Araujo, E. D., Rosa, D. A., Park, J., Tin, G., Ahmar, S., Gunning, P. T., Bock, C., Siddle, H. V., Woods, G. M., Kubicek, S., Murchison, E. P., Bennett, K. L., Moriggl, R. and Bergthaler, A.
The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease
Cancer Cell. 2019 Jan 14;35(1):125-139.e9. doi: 10.1016/j.ccell.2018.11.018
Wingelhofer, B., Neubauer, H.A., Valent, P., Han, X., Constantinescu, S., Gunning, P.T., Müller, M. and Moriggl, R.
Implications of STAT3 and STAT5 signaling on gene regulation and chromatin remodeling in hematopoietic cancer
Leukemia. 2018 March 27. doi:10.1038/s41375-018-0117-x
Sternberg, C., Gruber, W., Eberl, M., Tesanovic, S., Stadler, M., Elmer, D. P., Schlederer, M., Grund, S., Roos, S., Wolff, F., Kaur, S., Mangelberger, D., Lehrach, H., Hache, H., Wierling, C., Laimer, J., Lackner, P., Wiederstein, M., Kasper, M., Risch, A., Petzelbauer, P., Moriggl, R., Kenner, L. and Aberger, F.
Synergistic Cross-Talk of Hedgehog and Interleukin-6 Signaling Drives Growth of Basal Cell Carcinoma
Int J Cancer. 2018 Jul 10. doi: 10.1002/ijc.31724
Prutsch, N., Gurnhofer, E., Suske, T., Liang, H. C., Schlederer, M., Roos, S., Wu, L. C., Simonitsch-Klupp, I., Alvarez-Hernandez, A., Kornauth, C., Leone, D. A., Svinka, J., Eferl, R., Limberger, T., Aufinger, A., Shirsath, N., Wolf, P., Hielscher, T., Aberger, F., Schmoellerl, J., Stoiber, D., Strobl, B., Jager, U., Staber, P. B., Grebien, F., Moriggl, R., Muller, M., Inghirami, G. G., Sanda, T., Look, A. T., Turner, S. D., Kenner, L. and Merkel, O.
Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma
Leukemia. 2018 Aug 21. pii: 10.1038/s41375-018-0239-1. doi: 10.1038/s41375-018-0239-1
Pham, H. T. T., Hengstschlager, M. and Moriggl, R.
A haunted beast: Targeting STAT5BN642H in T-Cell Neoplasia
Mol Cell Oncol. 2018 Mar 28;5(3):e1435181. doi: 10.1080/23723556.2018.1435181. eCollection 2018.
Moll, H. P., Pranz, K., Musteanu, M., Grabner, B., Hruschka, N., Mohrherr, J., Aigner, P., Stiedl, P., Brcic, L., Laszlo, V., Schramek, D., Moriggl, R., Eferl, R., Moldvay, J., Dezso, K., Lopez-Casas, P. P., Stoiber, D., Hidalgo, M., Penninger, J., Sibilia, M., Gyorffy, B., Barbacid, M., Dome, B., Popper, H. and Casanova, E.
Afatinib restrains K-RAS-driven lung tumorigenesis
Sci Transl Med. 2018 Jun 20;10(446). pii: 10/446/eaao2301. doi: 10.1126/scitranslmed.aao2301
Kaltenecker, D., Themanns, M., Mueller, K.M., Spirk, K., Suske, T., Merkel, O., Kenner, L., Luís, A., Kozlov, A., Haybaeck, J., Müller, M., Han, X. and Moriggl, R.
Hepatic growth hormone - JAK2 - STAT5 signalling: Metabolic function, non-alcoholic fatty liver disease and hepatocellular carcinoma progression
Cytokine.2018 Oct 30. doi: 10.1016/j.cyto.2018.10.010
Kaltenecker, D., Themanns, M., Mueller, K. M., Spirk, K., Golob-Schwarzl, N., Friedbichler, K., Kenner, L., Haybaeck, J. and Moriggl, R.
STAT5 deficiency in hepatocytes reduces diethylnitrosamine-induced liver tumorigenesis in mice
Cytokine. 2018 Oct 27. pii: S1043-4666(18)30402-2. doi: 10.1016/j.cyto.2018.10.014
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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:
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
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
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
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
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
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
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
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
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/
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
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
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:
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
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
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
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
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
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
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
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
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
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:
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:
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
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
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:
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
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., 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
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
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
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
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
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
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
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:
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
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
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:
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
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
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:
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
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
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
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
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:
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
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.
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
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
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