Veronika Sexl, MD
Insitute of Pharmacology and Toxicology
Our lab has a long standing interest in leukemogenesis and NK-cell mediated tumor surveillance. Natural killer (NK) cells represent an important arm of the innate immune system being the first line of defence against transformed cells. Their cytolytic capacity towards malignant cells renders them a highly attractive point of therapeutic intervention. Recently, immune-based strategies have been recognized as major break-through in medicine – NK cells being postulated a powerful weapon against a variety of solid cancers and leukemia. NK cell-based therapies are also envisioned a powerful option for treating minimal residual disease and for the prevention of metastasis. It therefore appears of utmost importance to understand which signalling pathways and key molecular players control and mediate NK cell development and function.
Kovacic B, Stoiber D, Moriggl R, Weisz E, Ott RG, Kreibich R, Levy DE, Beug H, Freissmuth M, Sexl V. STAT1 acts as a tumor promoter for leukemia development. Cancer Cell. 2006 Jul;10(1):77-87.
Eckelhart E, Warsch W, Zebedin E, Simma O, Stoiber D, Kolbe T, Rülicke T, Müller M, Casanova E, Sexl V. A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK-cell survival and development. Blood. 2011 Feb 3;117(5):1565-73. doi: 10.1182/blood-2010-06-291633. Epub 2010 Dec 2.
Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott R, Schäfer M, Fajmann S, Schlederer M, Schiefer AI, Reichart U, Mayerhofer M, Hoeller C, Zoechbauer-Mueller S, Kerjaschki D, Bock C, Kenner L, Hoefler G, Freissmuth M, Green AR, Moriggl R, Busslinger M, Malumbres M, Sexl V. A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis. Cancer Cell. 2013 Aug 12;24(2):167-81. doi: 10.1016/j.ccr.2013.07.012.
Putz EM, Gotthardt D, Hoermann G, Csiszar A, Wirth S, Berger A, Straka E, Rigler D, Wallner B, Jamieson AM, Pickl WF, Zebedin-Brandl EM, Müller M, Decker T, Sexl V. CDK8-mediated STAT1-S727 phosphorylation restrains NK cell cytotoxicity and tumor surveillance. Cell Rep. 2013 Aug 15;4(3):437-44. doi: 10.1016/j.celrep.2013.07.012. Epub 2013 Aug 8.
Gotthardt D, Putz EM, Grundschober E, Prchal-Murphy M, Straka E, Kudweis P, Heller G, Bago-Horvath Z, Witalisz-Siepracka A, Cumaraswamy AA, Gunning PT, Strobl B, Müller M, Moriggl R, Stockmann C, Sexl V. Stat5 is a key regulator in NK cells and acts as molecular switch from tumor surveillance to tumor promotion. Cancer Discovery. 2016 Apr;6(4):414-29. doi: 10.1158/2159-8290.CD-15-0732. Epub 2016 Feb 12.