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