The SFB members Birgit Strobl, Mathias Müller and Richard Moriggl show in complex mouse models and human cells the pivotal role of TYK2 in the development of severe organ damage during endotoxemia. Mechanistically the TYK2-dependent pathology was driven by murine caspase-11 (CASP11) or the human homolog CASP5 activity and the subsequent release of IL-1ß and IL-18.

Published in Cell Death & Differentiation

Andrea Poelzl, Caroline Lassnig, Sabine Tangermann, Dominika Hromadová, Ursula Reichart, Riem Gawish, Kristina Mueller, Richard Moriggl, Andreas Linkermann, Martin Glösmann, Lukas Kenner, Mathias Mueller & Birgit Strobl
TYK2 licenses non-canonical inflammasome activation during endotoxemia

https://doi.org/10.1038/s41418-020-00621-x

 

Using sophisticated genetically engineered mouse models the SFB members Birgit Strobl, Mathias Müller and Veronika Sexl further dissect the NK cell-intrinsic and -extrinsic requirements for STAT1a versus STAT1b in NK cell biology and tumor surveillance.

Published in Frontiers in Immunology

Kartin Meissl, Natalija Simonović, Lena Amenitsch, Agnieszka Witalisz-Siepracka, Klara Klein, Caroline Lassnig, Ana Puga, Claus Vogl, Andrea Poelzl, Markus Bosmann, Alexander Dohnal, Veronika Sexl, Mathias Müller & Birgit Strobl

STAT1 isoforms differentially regulate NK cell maturation and anti-tumour activity

https://doi.org/10.3389/fimmu.2020.02189

 

 

We are pleased to announce the second Cold Spring Harbor winter 2020 conference on JAK-STAT Pathways in Health & Disease, which will begin at 7:30 pm on Monday, April 6 and run through lunch on Thursday, April 9. 

Topics:

  • Jak-STAT Mutations and Genomic Functions
  • JAK-STAT Signaling in the Hematopoietic System
  • STAT3, Metabolism and Cancer
  • JAK-STAT Signaling and Regulation
  • Transcriptional and Epigenetic Regulation by STATs
  • JAK-STAT Inhibition

https://meetings.cshl.edu/meetings.aspx?meet=stats&year=20

cold spring harbor labratory

Therapeutic targeting of STAT3 by monobodies

An international consortium headed by the Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences ETH Lausanne collaborated with Veronika Sexl group members and developed the first monobodies targeted against STAT3. Monobodies are synthetic binding proteins engineered to selectively bind intracellular proteins – also those lacking an enzymatic domain. High affinity STAT3 monobodies were identified in a combinatorial phage and yeast display library sorting screen. The authors show selective interference of the monobodies with cellular STAT3 activity. This is an attractive therapeutic option due to STAT3’s homology with other STAT proteins that complicates the development of selective inhibitors.

Published in Nature Communications

Grégory La Sala, Camille Michiels, Tim Kükenshöner, Tania Brandstoetter, Barbara Maurer, Akiko Koide, Kelvin Lau, Florence Pojer, Shohei Koide, Veronika Sexl, Laure Dumoutier & Oliver Hantschel

Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains

Doi: https://doi.org/10.1038/s41467-020-17920-z

 

Nikolaus Fortelny and Christoph Bock of CeMM showed the usefulness of knowledge-primed neural networks (KPNNs) for the interpretation of single-cell RNA-seq data. They expect that the use of deep learning on biological networks will also be relevant in other areas of biomedicine analysing big data sets, including metabolomics, proteomics and cellular or cognitive networks.

Published in Genome Biology

Nikolaus Fortelny and Christoph Bock

Knowledge-primed neural networks enable biologically interpretable deep learning on single-cell sequencing data

Doi: https://doi.org/10.1186/s13059-020-02100-5

Special Issue ‚Targeting STAT3 and STAT5 in Cancer’ with Guest Editors Richard Moriggl (Vienna, AT), Patrick Gunning (Toronto, CA) and György Miklós Keserü (Budapest, HU). The Editorial of this Special Issue of Cancers (Basel) is now published: https://www.mdpi.com/2072-6694/12/8/2002.

The Special Issue contains various contributions of SFB members and associate members: https://www.mdpi.com/journal/cancers/special_issues/STAT_cancers

The mammalian immune system implements a remarkably effective set of mechanisms for fighting pathogens. Its main components are haematopoietic immune cells, including myeloid cells that control innate immunity, and lymphoid cells that constitute adaptive immunity. However, immune functions are not unique to haematopoietic cells, and many other cell types display basic mechanisms of pathogen defence. This study highlights the prevalence and organ-specific complexity of immune gene activity in non-haematopoietic structural cells, and it provides a high-resolution, multi-omics atlas of the epigenetic and transcriptional networks that regulate structural cells in the mouse.

Nature News and Views: https://www.nature.com/articles/d41586-020-01916-2

Article: https://www.nature.com/articles/s41586-020-2424-4

The conference will be held at the Grecotel Kos Imperial, Kos, Greece on May 26 - 31, 2021.

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 (www.aegeanconferences.org). Registration will be limited to 80-110 participants for this meeting; therefore, there should be ample opportunities for interactions and discussions.

Please click this link (http://www.aegeanconferences.org/src/App/conferences/view/150) to go to the Aegean Conferences 4th International Conference on Cytokines in Cancer meeting website for further info.

Acute myeloid leukemia (AML) is an aggressive form of blood cancer that affects children and adults. In cases with particularly poor prognosis, this cancer is triggered by oncogenic fusion proteins, the formation of which involves the Nucleoporin 98 (NUP98) gene. A study published in the journal Blood results from a collaborative effort, including the groups of Richard Moriggl and Veronika Sexl of the Vetmeduni Vienna, and introduces a new therapeutic approach to fight this disease.

Genetic rearrangements, in which the NUP98 gene is involved, are rare genetic events that occur repeatedly in AML patients and are associated with a particularly poor prognosis - especially if this process occurs in children and adolescents. In a cooperation that included the Institute of Biochemistry and the Institute of Pharmacology at the Vetmeduni Vienna, researchers have for the first time identified the genes that are activated directly by NUP98 fusion proteins.

The authors developed novel mouse models that mimic the rare blood cancer AML, which included NUP98-fusion proteins. By integrating chromatin occupancy profiles of NUP98-fusion proteins with transcriptome profiling they discovered that NUP98-fusion proteins directly regulate leukemia-associated gene expression programs. Among these is the CDK6 protein, for which molecular inhibitors were already approved for clinical usage to treat other types of cancer. The authors then showed that treatment with CDK6 inhibitors significantly improved the survival of the test animals. Further clinical studies are now required to confirm the effectiveness of targeted CDK6 inhibition in patients suffering from AML.

Johannes Schmöllerl, Inês Amorim Monteiro Barbosa, Thomas Eder, Tania Brandstoetter, Luisa Schmidt, Barbara Maurer, Selina Troester, Ha Thi Thanh Pham, Mohanty Sagarajit, Jessica Ebner, Gabriele Manhart, Ezgi Aslan, Stefan Terlecki-Zaniewicz, Christa Van der Veen, Gregor Hoermann, Nicolas Duployez, Arnaud Petit, Helene Lapillonne, Alexandre Puissant, Raphael Itzykson, Richard Moriggl, Michael Heuser, Roland Meisel, Peter Valent, Veronika Sexl, Johannes Zuber and Florian Grebien

Doi: https://doi.org/10.1182/blood.2019003267