Two publications from the Institute of Pharmacology and Toxicology at Vetmeduni Vienna were awarded prizes. The article "STAT5 is a key regulator in NK cells and acts as molecular switch from tumor surveillance to tumor promotion", published in Cancer Discovery, received the research award from the City of Vienna Fund for innovative cancer research. The renowned Theodor Billroth Prize of the Vienna Medical Association was awarded to the publication "Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1 / 2 inhibitor therapy", published in Blood.

The City of Vienna Fund for Innovative Interdisciplinary Cancer Research is an initiative to support science and research in Vienna and to strengthen its importance in the public consciousness. This year's research funding award goes to a publication by first author Dagmar Gotthardt and last author Veronika Sexl from the Institute of Pharmacology and Toxicology at Vetmeduni Vienna. The research group showed for the first time that natural killer cells produce a factor (VEGF-A; Vascular Endothelial Growth Factor A) that can promote tumour growth. This study also defines STAT5 as a master regulator of NK-cell proliferation and lytic functions. Link to the publication can be found here.

The Theodor Billroth Prize of the Vienna Medical Association was awarded to another study led by Veronika Sexl, including first authors Edit Porpaczy (MedUni Vienna), Sabrina Tripolt and Andrea Hölbl-Kovacic (Vetmeduni Vienna). The results of this study show a risk for patients with the rare bone marrow disease myelofibrosis when treated with a JAK1/2 inhibitor, which is commonly used as a standard drug. Founded by the Vienna Chamber of Physicians, the Theodor Billroth Prize supports young academics and scientific activities. The Prize was awarded on December 17th 2018 in Vienna. Link to the publication can be found here.

The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway is critical in tuning immune responses and its dysregulation is tightly associated with cancer and immune disorders. Disruption of interleukin (IL)-15/STAT5 signaling pathway due to the loss of IL-15 receptor chains, JAK3 or STAT5 leads to immune deficiencies with natural killer (NK) cell abnormalities. JAK1, together with JAK3 transmits signals downstream of IL-15, but the exact contribution of JAK1 to NK cell biology remains to be elucidated. In this study we show that deletion of NK cell-intrinsic JAK1 leads to an almost complete loss of NK cells in the spleen, blood, and liver, proving a crucial role of JAK1 in peripheral NK cells. The absence of one allele of Jak1 suffices to drastically impair NK cell function whereas the deletion of JAK2 in NK cells has no impact on their survival or maturation. We thus propose that in contrast to currently used JAK1/JAK2 inhibitors, the use of JAK2-specific inhibitors would be advantageous for the cancer patients by leaving NK cells intact.

Publication in Frontiers in Immunology

Agnieszka Witalisz-Siepracka, Klara Klein, Daniela Prinz, Nicoletta Leidenfrost, Gernot Schabbauer, Alexander Dohnal and Veronika Sexl

Loss of JAK1 Drives Innate Immune Deficiency (2019), doi: 10.3389/fimmu.2018.03108

See also Video:

The best scientific posters at the Vetmeduni Vienna and the winners of the new VetIdeas Poster Challenge were announced as part of the 'That's Vet' show. The Poster Award was decided in two categories by a jury of science journalists and also by the University Council. The winners of the VetIdeas Poster Challenge were determined in advance by a jury decision.

After a one-year hiatus, Vetmeduni Vienna received another poster award in the 2018 edition of these prizes. All posters from 2017 and 2018 were eligible to participate. The best posters were again determined based on the nominations of science journalists and this year also with the support of the new University Council. At the same time, a new competition format was launched this year, the VetIdeas Poster Challenge, supported by the “tecnet equity” and “Accent Gründerservice”. Individual researchers or research teams were able to present ideas and concepts that could be implemented as products or intellectual propriety. In two workshops, the participants also learned how to present their work in a poster format and in a pitch. The workshop ended with the presentation of the poster and a pitch in front of a jury.

the Aegean Conferences 4th International Conference on Cytokines in Cancer meeting website for further info.

SFB-associated PhD students receive prizes in the Annual Poster Awards of Vetmeduni Vienna 2018

STAT1 exists as two alternatively spliced isoforms, STAT1α and STAT1β; the latter lacks the C-terminal transactivation domain (TAD). Our previous study with gene-modified mice expressing only the STAT1β isoform (Stat1β/β) demonstrated that STAT1β is capable of inducing a subset of IFNγ-responsive genes but the reason for the gene-selectivity remained unclear. In this study we used primary macrophages form wild-type and Stat1β/β mice to characterize the role of the C-terminal TAD in the transactivation and cofactor recruitment to paradigmatic IFNγ-responsive genes. Our key discoveries are that the STAT1β isoform is differentially required for (i) the recruitment of the Mediator coactivator complex and the transition of poised RNA polymerase II (Pol II) into productive elongation, (ii) the association of the general transcription factors TFIIH and p-TEFb to promoter elements specifically at late time points after stimulation or (iii) the establishment of active histone marks and the recruitment of Pol II to the STAT1 and IRF1 co-regulated gene promoters.

Collectively, our results shed new light on the communication of STAT1 with the transcriptional machinery and provide mechanistic insights into isoform-specific transcriptional activities of STAT1.

Publication in Frontiers in Immunology

Matthias Parrini, Katrin Meissl, Mojoyinola Joanna Ola, Therese Lederer, Ana Puga, Sebastian Wienerroither, Pavel Kovarik, Thomas Decker, Mathias Müller  and Birgit Strobl

The C-Terminal Transactivation Domain of STAT1 Has a Gene-Specific Role in Transativation and Cofactor Recruitment (2018), doi: 10.3389/fimmu.2018.02879

RNA helicase DDX3X is important for many aspects of RNA metabolism and RNA translation. In addition, several publications have highlighted a role for DDX3X in immunity, as it contributes to the induction of type I IFNs. However, the in vivo relevance of DDX3X in cells of hematopoietic origin remains unexplored. Using mouse genetics, we demonstrate that DDX3X makes important contributions to innate immunity against pathogens beyond its role in IFN induction, by influencing hematopoiesis as well as the transcription of many antimicrobial genes. By comparison between cells from male or female animals we show that DDX3X functions are in part compensated by its Y-chromosomal homologue DDX3Y. This suggests that DDX3X may be one of the factors contributing to well-established differences of the male and female immune systems. 

Publication in PLoS Pathogens

Daniel Szappanos, Roland Tschismarov, Thomas Perlot, Sandra Westermayer, Katrin Fischer, Ekaterini Platanitis, Fabian Kallinger, Maria Novatchkova, Caroline Lassnig, Mathias Müller, Veronika Sexl, Keiryn L. Bennett, Michelle Foong-Sobis, Josef M. Penninger and Thomas Decker

The RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity (2018),

The Austrian Pharmacological Society has awarded the renowned Heribert Konzett Prize 2018 to Andrea Hölbl-Kovacic from the Institute of Pharmacology and Toxicology (in Veronika Sexl’s group). The award recognizes outstanding achievements in experimental and clinical pharmacology. This is the first time this prize is awarded to a member of the Vetmeduni Vienna. Andrea Hölbl-Kovacic convinced the selection with her excellent publication performance on the STAT5 protein and its role in the development of acute lymphoblastic leukemia.

Named after the renowned Austrian physician, pharmacologist and pioneer in the development of asthma drugs, the Heribert Konzett Prize is a high honour from the Austrian Pharmacological Society (APHAR). It is awarded annually to young scientists under 40 from the experimental field and clinical pharmacology, who have made outstanding achievements in this research field through independent, outstanding achievements, such as multiple publications in renowned specialist journals and third-party fundraising. On September 28, 2018, APHAR officially awarded the prize at a symposium in Graz, and for the first time to an employee of Vetmeduni Vienna. For her publications about STAT5’s role in leukemia, Andrea Hölbl-Kovacic previously received the Hans Horst Meyer Award from APHAR and the Funding Award from the City of Vienna Fund.

Anaplastic Large Cell Lymphomas (ALCL) is a rare type of lymphoma comprising approximately 16 percent of all T cell lymphomas. The molecular analysis of human tumour samples to find new, personalised therapeutic targets and their validation in tumour models has become a attractive approach in cancer research, which can advance clinical management of cancer patients. This is even more important for rare tumours, like ALCL, in which researchers rely on a very small number of patients. New research led by the international ERIA consortium and with the participation of the SFB members Richard Moriggl, Mathias Müller, Birgit Strobl has now identified that all sub-types of ALCL rely on the same signalling pathway for survival.

TYK2 is a member of the JAK family of tyrosine kinases that is involved in chromosomal translocation-induced fusion proteins found in some anaplastic large cell lymphomas (ALCL). Here the authors show that TYK2 is highly expressed in all cases of human ALCL and it prevents apoptotic cell death in ALCL human cell lines by increasing the expression of Mcl1, a pro-survival member of the BCL2 family. Moreover, TYK2 inhibitors are able to induce apoptosis in ALCL cells. Therefore, TYK2 represents an attractive drug target due to its unique enzymatic domain and TYK2-specific inhibitors show promise as novel targeted inhibitors for ALCL. This is an urging therapy that still needs to be developed to treat immunological disorders, such as rare lymphomas.

Publication in Leukemia
Nicole Prutsch, Elisabeth Gurnhofer, Tobias Suske, Huan Chang Liang, Michaela Schlederer, Simone Roos, Lawren C. Wu, Ingrid Simonitsch-Klupp, Andrea Alvarez-Hernandez, Christoph Kornauth, Dario A. Leone, Jasmin Svinka, Robert Eferl, Tanja Limberger, Astrid Aufinger, Nitesh Shirsath, Peter Wolf, Thomas Hielscher, Fritz Aberger, Johannes Schmoellerl, Dagmar Stoiber, Birgit Strobl, Ulrich Jäger, Philipp B. Staber, Florian Grebien, Richard Moriggl, Mathias Müller, Giorgio G. Inghirami, Takaomi Sanda, A. Thomas Look, Suzanne D. Turner, Lukas Kenner and Olaf Merkel


The conference will be held at the Sheraton Resort, Rhodes, Greece on June 2-7, 2019.

Organizing committee: Belinda Parker, Leonidas Platanias, Mathias Müller and Serge Y Fuchs.

The Conference is under the sponsorship of Aegean Conferences, a non-profit educational organization promoting science through focused scientific conferences ( Registration will be limited to 80-110 participants for this meeting; therefore, there should be ample opportunities for interactions and discussions.

The conference sessions present subject areas focused on:

Role of cytokines in tumor initiation, progression and metastatic disease

Anti-tumorigenic effects of interferons and other cytokines

Cytokine-mediated immune regulation and tumor microenvironment

Cytokines and cancer stem cells

Targeting cytokine pathways for anti-cancer treatment and therapeutic use of cytokines

The program details will be presented soon. Click here to download the flyer

Natascha Kleiter,
Section of Translational Cell Genetics,
Medical University Innsbruck

Title: The nuclear orphan receptor NR2F6 as a new cancer immune checkpoint

Natascha Kleiter has characterized NR2F6 as an intracellular immune checkpoint, directly repressing transcription of cytokine genes in T cells relevant for cancer cell rejection and therefore enhancing tumor immune surveillance.