Our work builds on a previously published paper (https://doi.org/10.1038/leu.2016.277) describing germ-line TYK2 gain-of-function (GOF) mutations identified in childhood leukemia. In close collaboration with the Dutch pediatric oncologists we studied the oncogenic and druggable properties of the two activating mutations of this JAK family member tyrosine kinase. We demonstrate the transformation capacity of the potent TYK2P760L mutation in various hematopoietic cell systems and its tumorigenic potential upon transplantation into mouse models. The highly selective TYK2 inhibitor deucravacitinib blocked GOF TYK2 activity. A screen for kinase pathways co-operating with oncogenic TYK2 identified the PI3K/AKT/mTOR and CDK4/6 pathways as top hits. Combinatorial treatment of the TYK2inib with blockers of these pathways turned out to be more efficacious than single treatments and could be successfully translated to PDX cells derived from the TYK2P760L mutation carrying patient. The original work with contributions from the SFB members Birgit Strobl, Veronika Sexl, Richard Moriggl and Mathias Müller establishes novel treatment options for acute leukemia in patients harboring GOF TYK2 mutations and has not been submitted to publication elsewhere.

Published in Haematologica

Katharina Wöss, Sabine Macho-Maschler, Dorette S. Van Ingen Schenau, Miriam Butler, Caroline Lassnig, Daniel Valcanover, Andrea Poelzl, Katrin Meissl, Barbara Maurer, Tania Brandstoetter, Claus Vogl, Anna Koren, Stefan Kubicek, Anna Orlova, Richard Moriggl, Birgit Strobl, Veronika Sexl, Frank N Van Leeuwen, Roland P Kuiper, Mathias Müller

Oncogenic TYK2P760L kinase is effectively targeted by combinatorial TYK2, mTOR and CDK4/6 kinase blockade


Wednesday January 12th 2022, 09 am

Olivia Majer

Max-Planck-Institut für Infektionsbiologie, Innate Immune Regulation, Berlin DE (https://www.mpiib-berlin.mpg.de/2000793/olivia-majer).

Title: Compartmentalized signaling control of endosomal TLRs maintains immune tolerance to self-nucleic acids

Host: Mathias Müller

Location: Zoom


Joint PhD Symposium Programme ‘It’s A Kind Of Magic’

November 16-17, 2021

The PhD students of the FWF-funded doctoral programs TissueHome and Inflammation And Immunity have organized the joint online conference ‘It’s A Kind Of Magic – One Golden Glance Of Immunology’. The event can be joined via registration at https://www.meduniwien.ac.at/web/ueber-uns/events/2021/its-a-kind-of-magic-joint-phd-symposium/.



Vetmeduni Vienna, January 25th 2021:

Extension of “Monarchies and Hierarchies in Shaping Chromatin Landscapes” Special Research Programme funded by Austrian Science Fund FWF



Second funding period (2021-2025) for SFB F61 approved in the FWF Board meeting from 23rd to 25th of November 2020.


Summary of the Research Program

The STAT proteins are transcription factors with a central role in cell homeostasis, survival and differentiation. They are activated by the JAK kinases, including TYK2. Dysregulated STATs cause immune- or inflammation-related, metabolic and tumorigenic diseases but how STATs interact with chromatin is unknown. We have compiled a map of chromatin activity for all wildtype STATs, TYK2, oncogenic STAT5B and a kinase-inactive TYK2 mutant in primary immune cells and in structural cells under homeostatic, cytokine-induced and cell-transforming conditions and plan to use it to determine how JAK-STAT exerts its manifold effects.

The SFB groups hypothesise

  • STATs and TYK2 cause chromatin remodeling in non-hematopoietic cells, defining their identity and shaping the interface of immune cells and stromal cells in homeostasis and disease (Christoph Bock, Mathias Müller, Birgit Strobl with all other consortium members)
  • Homeostatic macrophages use STAT2/IRF9 to prime themselves for activation (Thomas Decker, Sylvia Knapp and Christoph Bock); signals from STAT1,3,5 drive the exit from and the return to homeostasis (Sylvia Knapp, Mathias Müller, Birgit Strobl, Thomas Decker and Christoph Bock)
  • STAT5A and STAT5B are not equivalent but drive distinct developmental programs in haematopoietic and leukaemic cells (Veronika Sexl, Heidi Neubauer and Christoph Bock)
  • The chromatin signatures of haematopoietic cancers are shaped by oncogenic STAT5, oncogenic STAT3 or a STAT3-CDK6 complex (Veronika Sexl, Heidi Neubauer and Christoph Bock)
  • TYK2 determines cell fate by regulating both transcriptional and post-transcriptional processes (Birgit Strobl, Mathias Müller and Christoph Bock with Thomas Decker).


Much of the current work on signal transduction in disease conditions (e.g. during infection, transformation or drug treatment) is based on an outdated understanding of the homeostatic healthy condition. By providing a fine-scale and cell-specific definition, our work will cause a comprehensive (re-)evaluation of the early stages of perturbations and the return to homeostasis. The approach is completely novel and will revolutionize our understanding of cellular memory and the progression/resolution of disease.

Press Release

In Q2 2021 a common seminar series of the FWF-funded Vienna Life Science Region research consortia of DocFund TissueHome (speakers Karl Kuchler & Birgit Strobl; https://tissuehome.meduniwien.ac.at), SFB HIT: HADCs – Immunomolulation – T cells (speaker Willfried Ellmeier; https://www-new.meduniwien.ac.at/HIT/) and the SFB JAK-STAT & Chromatin Landscapes (speakers Mathias Müller & Thomas Decker) will start. Please look out for the upcoming announcements.

Press Release

Joined forces of FWF SFB with DFG TRR:

the Viennese JAK-STAT consortium and the DFG funded Transregio (TRR) research consortium ‘Determinants and Dynamics of Elimination versus Persistence of Hepatitis Virus Infection’ (TRR179) coordinated by Ralf Bartenschlager (http://www.trr179.de/en/) initiated a collaboration with future researcher exchanges and lab visitations.

Press Release

Ralf Bartenschlager,
Head of Research Group Viral Hepatitis and Liver Cancer at DKFZ Heidelberg DE,
Head of Department Molecular Virology at Heidelberg University Hospital,
Speaker of DFG funded research consortium TRR179 Determinants and Dynamics of Elimination versus Persistence of Hepatitis Virus Infection,

TRR179: A collaborative research network on hepatitis virus persistence and antiviral immunity

Date: 03 March 2021, 10am



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