Partners in crime: STAT3 and CDK6 control transformation in hematopoietic cells
Oncogenes teaming up – activated STAT3 and STAT5 shaping chromatin in connection with CDK6
NETWORK CONTRIBUTION
We propose a novel mode by which STAT3 regulates the chromatin landscape in transformed haematopoietic cells in cooperation with the cell cycle regulator CDK6. We shall test this notion by means of BCR ABL+ and NPM-ALK+ tumors.. If either STAT3 or CDK6 is absent, tumor formation is severely reduced. Our preliminary studies suggest a tight interaction of STAT3 and CDK6 on chromatin, which we intend to investigate further. Our investigations will include the STAT3 mutations that have been repeatedly found in human lymphoid malignancies. These clinically relevant STAT3 mutations will be studied in model cell lines and in vitro and in vivo in B and T lymphoid cells.
Our major goal is to test the ability of lymphocytes to propagate leukaemia, their epigenetic landscape and their interaction with CDK6. The work should reveal a novel layer of regulation of STAT3, mediated via its interaction with CDK6 and might open a novel therapeutic avenue to interfere with STAT3´s function.
Within the proposed project we aim to determine the stepwise cooperativity of STAT3 and TFs in gene induction and histone modification.
CONTACT
Institut für Tierzucht und Genetik
Veterinärmedizinische Universität Wien
Veterinärplatz 1
A-1210 Vienna
Austria
PUBLICATIONS
SFB-F61 / F28 related publications - Former Group Sexl
| 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 |
| 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. |
| Ott, R.G., Simma, O., Kollmann, K., Weisz, E., Zebedin, E.M., Schorpp-Kistner, M., Heller, G., Zochbauer, S., Wagner, E.F., Freissmuth, M. and Sexl, V. (2007). Jun B is a gatekeeper for B-lymphoid leukemia. Oncogene 26:4863-71. doi: 10.1038/sj.onc.1210285 |
| Staber, P.B., Vesely, P., Haq, N., Ott, R.G., Funato, K., Bambach, I., Fuchs, C., Schauer, S., Linkesch, W., Hrzenjak, A., Dirks, W.G., Sexl, V., Bergler, H., Kadin, M.E., Sternberg, D.W., Kenner, L. and Hoefler, G. (2007). The oncoprotein NPM-ALK of anaplastic large cell lymphoma induces JUNB transcription via ERK1/2 abd JunB translation via mTOR signaling. Blood 110:3374-83. doi: http://dx.doi.org/10.1182/blood-2007-02-071258 |
| 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 |
| Schuster, C., Mueller, M., Freissmuth, M., Sexl, V. and Stoiber, D. (2008). Commentary on H.Ide et al: “Tyk2 expression and its signaling enhances invasiveness of prostate cancer cellsâ€. Biochem Biophys Res Commun 366:869-70. doi: 10.1016/j.bbrc.2007.12.017 |
| Kornfeld, J.W., Grebien, F., Kerenyi, M.A., Friedbichler, K., Kovacic, B., Zankl, B., Hoelbl, A., Nivarti, H., Beug, H., Sexl, V., Mueller, M., Kenner, L., Muellner, 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 |
| Mayerhofer, M., Gleixner, K.V., Mayerhofer, J., Hoermann, G., Jaeger, E., Aichberger, K.J., Ott, R.G., Greish, K., Nakamura, H., Derdak, S., Samorapoompichit, P., Pickl, W.F., Sexl, V., Esterbauer, H., Schwarzinger, I., Sillaber, C., Maeda, H. and Valent, P. (2008). Targeting of heat shock protein 32 (Hsp 32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myleoid leukemia. A novel approach to overcome resistance against imatinib. Blood 111:2200-14. doi: http://dx.doi.org/10.1182/blood-2006-11-055723 |
| Zebedin, E., Simma, O., Schuster, C., Putz, E.M., Fajmann, S., Warsch, W., Eckelhart, E., Stoiber, D., Weisz, E., Schmid, J.A., Pickl, W.F., Baumgartner, C., Valent, P., Piekorz, R.P., Freissmuth, M. and Sexl, V. (2008). Leukemic challenge unmasks a requirement for PI3Kdelta in NK cell-mediated tumor surveillance. Blood 112:4655-64. doi: 10.1182/blood-2008-02-139105 |
| Pilz, A., Kratky, W., Stockinger, S., Simma, O., Kalinke, U., Lingnau, K., von Gabain, A., Stoiber, D., Sexl, V., Kolbe, T., Rulicke, T., Mueller, M. and Decker, T. (2009). Dendritic cells require STAT-1 phosphorylated at its transactivating domain for the induction of peptide-specific CTL. J Immunol 183:2286-93. doi: 10.4049/jimmunol.0901383 |
| Simma, O., Zebedin, E., Neugebauer, N., Schellack, C., Pilz, A., Chang-Rodriguez, S., Lingnau, K., Weisz, E., Putz, E.M., Pickl, W.F., Felzmann, T., Mueller, M., Decker, T., Sexl, V. and Stoiber, D. (2009). Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillance. Cancer Res 69:203-11. doi: 10.1158/0008-5472.CAN-08-1705 |
| 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 |
| 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 |
| Beer-Hammer, S., Zebedin, E., von Holleben, M., Alferink, J., Reis, B., Dresing, P., Degrandi, D., Scheu, S., Hirsch, E., Sexl, V., Pfeffer, K., Nurnberg, B., and Piekorz, R.P. (2010). The catalytic PI3K isoforms F28110gamma and F28110delta contribute to B cell development and maintenance, transformation, and proliferation. J Leukoc Biol 87: 1083-1095. doi: 10.1189/jlb.0809585 |
| Eckelhart, E., Warsch, W., Zebedin, E., Simma, O., Stoiber, D., Kolbe, T., Rulicke, T., Mueller, M., Casanova, E., and Sexl, V. (2011). A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK cell survival and development. Blood 117: 1565-1573. doi: dx.doi.org/10.1182/blood-2010-06-291633 |
| 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 |
| Schneckenleithner, C., Bago-Horvath, Z., Dolznig, H., Neugebauer, N., Kollmann, K., Kolbe, T., Decker, T., Kerjaschki, D., Wagner, K.-U., Mueller, M., Stoiber, D., and Sexl, V. (2011). Putting the brakes on mammary tumorigenesis: Loss of STAT1 predisposes to intraepithelial neoplasias. Oncotarget 2: 1043-1054. online ISSN: 1949-2553 |
| Schuster*, C., Berger*, A., Hoelzl, M.A., Putz, E.M., Frenzel, A., Simma, O., Moritz, N., Hoelbl, A., Kovacic, B., Freissmuth, M., Mueller, M., Villunger, A., Mullauer, L., Schmatz, A.I., Streubel, B., Porpaczy, E., Jager, U., Stoiber, D., and Sexl, V. (2011). *equal contribution The cooperating mutation or "second hit" determines the immunological visibility towards MYC-induced murine lymphomas. Blood 118: 4635-4645. doi: http://dx.doi.org/10.1182/blood-2010-10-313098 |
| 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 |
| Strobl, B., Stoiber, D., Sexl, V., and Mueller, M. (2011). Tyrosine kinase 2 (Tyk2) in cytokine signalling and host immunity. Front Biosci 17: 3224-3232. [review] doi: http://dx.doi.org/10.2741/3908 |
| Kollmann, K., Heller, G., Ott, R.G., Scheicher, R., Zebedin-Brandl, E., Schneckenleithner, C., Simma, O., Warsch, W., Eckelhart, E., Hoelbl, A., Bilban, M., Zochbauer-Muller, S., Malumbres, M., and Sexl, V. (2011). C-JUN promotes BCR-ABL induced lymphoid leukemia by inhibiting methylation of the 5' region of Cdk6. Blood 117: 4065-4075. doi: dx.doi.org/10.1182/blood-2010-07-299644 |
| 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 |
| Putz*, E.M., Prchal-Murphy*, M., Simma, O.A., Forster, F., Koenig, X., Stockinger, H., Piekorz, R.P., Freissmuth, M., Mueller, M., Sexl, V., and Zebedin-Brandl, E. (2012). *equal contribution PI3Kδ Is Essential for Tumor Clearance Mediated by Cytotoxic T Lymphocytes. PLoS One 7: e40852. doi: 10.1371/journal.pone.0040852 |
| 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 |
| Kernbauer, E., Maier, V., Stoiber, D., Strobl, B., Schneckenleithner, C., Sexl, V., Reichart, U., Kalinke, U., Reizis, B., Jamieson, A., Mueller, M., and Decker, T. (2012). Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection. PLoS Pathog 8: e1002763. doi: 10.1371/journal.ppat.1002763 |
| 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 |
| Mizutani*, T., Neugebauer*, N., Putz*, E.M., Moritz, N., Simma, O., Zebedin-Brandl, E., Gotthardt, D., Warsch, W., Eckelhart, E., Kantner, H.-P., Kalinke, U., Lienenklaus, S., Weiss, S., Strobl, B., Mueller, M., Sexl, V., and Stoiber, D. (2012). *equal contribution Conditional IFNAR1 ablation reveals distinct requirements of Type I IFN signaling for NK cell maturation and tumor surveillance. Oncoimmunology 1: 1027-1037. doi: 10.4161/onci.21284 |
| Hantschel*, O., Warsch*, W., Eckelhart, E., Kaupe, I., Grebien, F., Wagner, K.U., Superti-Furga, G., and Sexl, V. (2012). *equal contribution BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia. Nat Chem Biol 8: 285-293. doi: 10.1038/nchembio.775 |
| Putz, E.M., Zebedin, E., and Sexl, V. (2012). STAT Transcription Factors: Controlling All Aspects of NK Cell Biology. In Jak-Stat Signaling: From Basics to Disease (Decker, T. and Mueller, M., Eds.) Springer Wien Heidelberg New York Dordrecht London. pp. 187-204. [book chapter] doi: 10.1007/978-3-7091-0891-8_12 ISBN: 978-3-7091-0890-1 |
| 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-Mueller, 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 |
| Köpruelue, A.D., Kastner, R., Wienerroither, S., Lassnig, C., Putz, E.-M., Majer, O., Reutterer, B., Sexl, V., Kuchler, K., Mueller, M., Decker, T., and Ellmeier, W. (2013). The tyrosine kinase Btk regulates the macrophage response to Listeria monocytogenes infection. PLoS One 8: e60476. doi: 10.1371/journal.pone.0060476 |
| Putz, E.M., Gotthardt, D., Hoermann, G., Csiszar, A., Wirth, S., Berger, A., Straka, E., Rigler, D., Wallner, B., Jamieson, A.M., Pickl, W.F., Zebedin-Brandl, E.M., Mueller, M., Decker, T., and Sexl, V. (2013). CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance. Cell Rep 15: 437-444. doi: 10.1016/j.celrep.2013.07.012 |
| Hannesdottir, L., Tymoszuk, P., Parajuli, N., Wasmer, M.H., Philipp, S., Daschil, N., Datta, S., Koller, J.B., Tripp, C.H., Stoitzner, P., Muller-Holzner, E., Wiegers, G.J., Sexl, V., Villunger, A., and Doppler, W. (2013). Lapatinib and doxorubicin enhance the Stat1-dependent antitumor immune response. Eur J Immunol. 43: 2718-2729. doi: 10.1002/eji.201242505 |
| Kantner*, H.P., Warsch*, W., Delogu, A., Bauer, E., Esterbauer, H., Casanova, E., Sexl, V., and Stoiber, D. (2013). *equal contribution ETV6/RUNX1 Induces Reactive Oxygen Species and Drives the Accumulation of DNA Damage in B Cells. Neoplasia 15: 1292-1300. doi: 10.1593/neo.131310 |
| Richter, K., Perriard, G., Behrendt, R., Schwendener, R.A., Sexl, V., Dunn, R., Kamanaka, M., Flavell, R.A., Roers, A., and Oxenius, A. (2013). Macrophage and T cell produced IL-10 promotes vrial chronicity. PLoS Pathog 9: e1003735. doi: 10.1371/journal.ppat.1003735 |
| Warsch, W., Grundschober, E., and Sexl, V. (2013). Adding a new facet to STAT5 in CML: Multitasking for leukemic cells. Cell Cycle 12: 1813-1814. [editorial feature] doi: 10.4161/cc.25116 |
| Warsch, W., Walz, C., and Sexl, V. (2013). JAK of all trades: JAK2-STAT5 as novel therapeutic targets in BCR-ABL1+ chronic myeloid leukemia. Blood 122: 2167-2175. doi: dx.doi.org/10.1182/blood-2013-02-485573 |
| Koromilas, A.E., and Sexl, V. (2013). The tumor suppressor function of STAT1 in breast cancer. JAK-STAT 2:2, 1-5. [review] doi: 10.4161/jkst.23353 |
| 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 |
| Gotthardt, D., Putz, E.M., Straka, E., Kudweis, P., Biaggio, M., Poli, V., Strobl, B., Mueller, M., and Sexl, V. (2014). Loss of STAT3 in murine NK cells enhances NK cell-dependent tumor surveillance. Blood 124: 2370-2379. doi: http://dx.doi.org/10.1182/blood-2014-03-564450 |
| Kovacic, B., Hoelbl-Kovacic, A., Fischhuber, K.M., Leitner, N.R., Gotthardt, D., Casanova, E., Sexl, V., and Mueller, M. (2014). Lactotransferrin-Cre reporter mice trace neutrophils, monocytes/macrophages and distinct subtypes of dendritic cells. Haematologica 99: 1006-1015. doi: 10.3324/haematol.2013.097154 |
| Gotthardt, D., Prchal-Murphy, M., Seillet, C., Glasner, A., Mandelboim, O., Carotta, S., Sexl, V., and Putz, E.M. (2014). NK cell development in bone marrow and liver: site matters. Genes Immun 15: 584-587. doi: 10.1038/gene.2014.55 |
| Grundschober, E., Hoelbl-Kovacic, A., Bhagwat, N., Kovacic, B., Scheicher, R., Eckelhart, E., Kollmann, K., Keller, M., Grebien, F., Wagner, K.U., Levine, R.L., and Sexl, V. (2014). Acceleration of Bcr-Abl leukemia induced by deletion of JAK2. Leukemia 28: 1918-1922. doi: 10.1038/leu.2014.152 |
| Putz, E.M., Hoelzl, M.A., Baeck, J., Bago-Horvath, Z., Schuster, C., Reichholf, B., Kern, D., Aberger, F., Sexl, V., and Hoelbl-Kovacic, A. (2014). Loss of STAT3 in Lymphoma Relaxes NK Cell-Mediated Tumor Surveillance. Cancers 6: 193-210. doi: 10.3390/cancers6010193 |
| Klose, C.S., Flach, M., Mohle, L., Rogell, L., Hoyler, T., Ebert, K., Fabiunke, C., Pfeifer, D., Sexl, V., Fonseca-Pereira, D., Domingues, R.G., Veiga-Fernandes, H., Arnold, S.J., Busslinger, M., Dunay, I.R., Tanriver, Y., and Diefenbach, A. (2014). Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages. Cell 157: 340-356. |
| Pathria*, P., Gotthardt*, D., Prchal-Murphy*, M., Putz*, E.M., Holcmann, M., Schlederer, M., Grabner, B., Crncec, I., Svinka, J., Musteanu, M., Hoffmann, T., Filipits, M., Berger, W., Poli, V., Kenner, L., Bilban, M., Casanova, E., Mueller, M., Strobl, B., Bayer, E., Mohr, T., Sexl, V., and Eferl§, R. (2015). *equal contribution §SFB member of the 1st and 2nd funding period Myeloid STAT3 promotes formation of colitis-associated colorectal cancer in mice. Oncoimmunology 4(4):e998529. doi: 10.1080/2162402X.2014.998529 |
| Prchal-Murphy, M., Witalisz-Siepracka, A., Bednarik, K.T., Putz, E.M., Gotthardt, D., Meissl, K., Sexl, V., Mueller, M., and Strobl, B. (2015). In vivo tumor surveillance by NK cells requires TYK2 but not TYK2 kinase activity. Oncoimmunology. doi: 10.1080/2162402X.2015.1047579 |
| Schneckenleithner, C., Hoelbl-Kovacic, A., and Sexl, V. (2015). Modeling BCR/ABL-Driven Malignancies in the Mouse. Methods in Mol Biol 1267: 263-282. [review] doi: 10.1007/978-1-4939-2297-0_12 |
| Bottos, A., Gotthardt, D., Gill, J.W., Gattelli, A., Frei, A., Tzankov, A., Sexl, V., Wodnar-Filipowicz, A., and Hynes, N.E. (2016). Decreased NK-cell tumour immunosurveillance consequent to JAK inhibition enhances metastasis in breast cancer models. Nat Commun 7, 12258. |
| Gotthardt, D., Putz, E.M., Grundschober, E., Prchal-Murphy, M., Straka, E., Kudweis, P., Heller, G., Bago-Horvath, Z., Witalisz-Siepracka, A., Cumaraswamy, A.A., Gunning, P.T., Strobl, B., Muller, M., Moriggl, R., Stockmann, C., and Sexl, V. (2016). STAT5 is a key regulator in NK cells and acts as molecular switch from tumor surveillance to tumor promotion. Cancer discovery 6, 414-429 |
| Klose, R., Krzywinska, E., Castells, M., Gotthardt, D., Putz, E.M., Kantari-Mimoun, C., Chikdene, N., Meinecke, A.K., Schrodter, K., Helfrich, I., Fandrey, J., Sexl, V., and Stockmann, C. (2016). Targeting VEGF-A in myeloid cells enhances natural killer cell responses to chemotherapy and ameliorates cachexia. Nat Commun 7, 12528 |
| Majoros, A., Platanitis, E., Szappanos, D., Cheoan, H.J., Vogl, C., Shukla, P., Stark, G.R., Sexl, V., Schreiber, R.D., Schindler, C., Mueller, M., and Decker, T. (2016). Response to interferons and antibacterial innate immunity in absence of tyrosine-phosphorylated STAT1. EMBO Rep 17, 367-382 |
| Putz, E.M., Majoros, A., Gotthart, D., Prchal-Murphy, M., Zebedin-Brandl, E., Fux, D.A., Schlattl, A., Schreiber, R.D., Carotta, S., Mueller, M., Gerner, C., Decker, T., and Sexl, V. (2016). Novel non-Âcanonical role of STAT1 in Natural Killer cell cytotoxicity. OncoImmunology 10.1080/2162402X.2016.1186314. |
| 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 |
| Linke, M., Pham, H.T., Katholnig, K., Schnoller, T., Miller, A., Demel, F., Schutz, B., Rosner, M., Kovacic, B., Sukhbaatar, N., Niederreiter, B., Bluml, S., Kuess, P., Sexl, V., Muller, M., Mikula, M., Weckwerth, W., Haschemi, A., Susani, M., Hengstschlager, M., Gambello, M.J., and Weichhart, T. (2017). Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression. Nat Immunol 10.1038/ni.3655 |
| Maurer, B., Farlik, M., and Sexl, V. (2017). It is a differentiation game: STAT5 in a new role. Cell Death Differ 10.1038/cdd.2017.71, 953-954 |
| Glasner, A., Levi, A., Enk, J., Isaacson, B., Viukov, S., Orlanski, S., Scope, A., Neuman, T., Enk, C.D., Hanna, J.H., Sexl, V., Jonjic, S., Seliger, B., Zitvogel, L., and Mandelboim, O. (2018). NKp46 Receptor-Mediated Interferon-gamma Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis. Immunity 10.1016/j.immuni.2017.12.007 |
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| Lehmann, F. M., von Burg, N., Ivanek, R., Teufel, C., Horvath, E., Peter, A., Turchinovich, G., Staehli, D., Eichlisberger, T., Gomez de Aguero, M., Coto-Llerena, M., Prchal-Murphy, M., Sexl, V., Bentires-Alj, M., Mueller, C. and Finke, D. Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation Nat Commun. 2020 Apr 14;11(1):1794. doi: 10.1038/s41467-020-15612-2 |
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| La Sala, G., Michiels, C., Kuekenshöner, T., Brandstoetter, T., Maurer, B., Koide, A., Lau, K., Pojer, F., Koide, S., Sexl, V., Dumoutier, L., and Hantschel, O. Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains Nat Commun 11, 4115. Doi: 10.1038/s41467-020-17920-z |
| Demiroz, D., Platanitis, E., Bryant, M., Fischer, P., Prchal-Murphy, M., Lercher, A., Lassnig, C., Baccarini, M., Mueller, M., Bergthaler, A., Sexl, V., Dolezal, M., and Decker, T. Listeria monocytogenes infection rewires host metabolism with regulatory input from type I interferons PLoS Pathog 2021 Jul 8;17, e1009697. doi: 10.1371/journal.ppat.1009697 |
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| Gorki, A.D., Symmank, D., Zahalka, S., Lakovits, K., Hladik, A., Langer, B., Maurer, B., Sexl, V., Kain, R., and Knapp, S. Murine ex vivo Cultured Alveolar Macrophages Provide a Novel Tool to Study Tissue-Resident Macrophage Behavior and Function Am J Respir Cell Mol Biol 66, 64-75. Doi: 10.1165/rcmb.2021-0190OC |
| Maurer, B., Brandstoetter, T., Kollmann, S., Sexl, V., and Prchal-Murphy, M. Inducible deletion of CDK4 and CDK6 - deciphering CDK4/6 inhibitor effects in the hematopoietic system Haematologica 106, 2624-2632. Doi: 10.3324/haematol.2020.256313 |
| Woess, K., Macho-Maschler, S., Van Ingen Schenau, D.S., Butler, M., Lassnig, C., Valcanover, D., Poelzl, A., Meissl, K., Maurer, B., Brandstoetter, T., Vogl, C., Koren, A., Kubicek, S., Orlova, A., Moriggl, R., Strobl, B., Sexl, V., Van Leeuwen, F.N., Kuiper, R.P., and Mueller, M. Oncogenic TYK2(P760L) kinase is effectively targeted by combinatorial TYK2, mTOR and CDK4/6 kinase blockade Haematologica 2022 Jan 13. doi: 10.3324/haematol.2021.279848 |
| Boccuni, L., Podgorschek, E., Schmiedeberg, M., Platanitis, E., Traxler, P., Fischer, P., Schirripa, A., Novoszel, P., Nebreda, A.R., Arthur, J.S.C., Fortelny, N., Farlik, M., Sexl, V., Bock, C., Sibilia, M., Kovarik, P., Mueller, M., and Decker, T. Stress signaling boosts interferon-induced gene transcription in macrophages. DOI 10.1126/scisignal.abq5389 |
| Brandstoetter, T., Schmoellerl, J., Grausenburger, R., Kollmann, S., Doma, E., Huuhtanen, J., Klampfl, T., Eder, T., Grebien, F., Hoermann, G., Zuber, J., Mustjoki, S., Maurer, B., and Sexl, V. SBNO2 is a critical mediator of STAT3-driven hematological malignancies. DOI 10.1182/blood.2022018494 |
| Woess, K., Macho-Maschler, S., Van Ingen Schenau, D.S., Butler, M., Lassnig, C., Valcanover, D., Poelzl, A., Meissl, K., Maurer, B., Brandstoetter, T., Vogl, C., Koren, A., Kubicek, S., Orlova, A., Moriggl, R., Strobl, B., Sexl, V., Van Leeuwen, F.N., Kuiper, R.P., and Mueller, M. Oncogenic TYK2(P760L) kinase is effectively targeted by combinatorial TYK2, mTOR and CDK4/6 kinase blockade. DOI doi.org/10.3324/haematol.2021.279848 |
