Group Pavel Kovarik

Signaling and gene expression in inflammation

On this page

The Question

Not Too Little, Not Too Much, Just Right.

Effective defense against infectious agents and tissue-damaging cues requires rapid activation of inflammatory responses, followed by the timely re-establishment of immune homeostasis once the microbial threats have been eliminated. Insufficient responses lead to infectious disease, whereas failures in homeostatic control result in tissue damage and impaired healing. Therefore, inflammatory responses must be strong, but also precisely regulated in magnitude and duration. Our research aims to understand molecular mechanisms that drive the precise balance between pro- and anti-inflammatory processes and how these processes are coordinated such that healthy immunity is maintained.

The Approach

We investigate immune homeostasis and balanced immune responses in 3 areas:

1) mRNA decay. mRNA decay is fundamental for immune homeostasis and control of inflammation. We employ genome-wide approaches, systems biology and organismal models to reveal mechanisms defining the timely and selective removal of inflammation-associated mRNAs.

2) Transcription regulation by Mediator kinase. We investigate how Mediator kinase precisely adjusts transcriptional responses during inflammation using infection models, biochemistry, proteomics and genome-wide assays.

3) Cell signaling. We employ infection models to understand how cells and organisms integrate external and internal signaling events to launch efficient immune responses against pathogens.

Pavel Kovarik

Pavel Kovarik studied molecular biology and biochemistry at universities in Brno and Vienna. He received PhD in biochemistry from the University of Vienna in 1995. In 2003 he became associate professor at Max F. Perutz Laboratories, University of Vienna, where is was promoted to full Professor of Immunobiology in 2012. He has been director of the Vienna Biocenter PhD Program since 2022. He coordinated several national and European research projects. 

Download CV

Main Building
Room: 4.615

   +43 1 4277 54608

Spotlights

Inflammation is controlled by mRNA fate decision in the nucleus

The fidelity of immune responses depends on timely controlled and selective degradation of mRNAs coding for inflammatory mediators such as cytokines. It remained unclear whether the selection of an individual mRNA molecule for degradation is a stochastic or regulated process. By studying the hierarchy of mRNA decay, we revealed that the fate of a given mRNA molecule is decided already during its synthesis by binding of the RNA-destabilizing protein TTP to pre-mRNA in the cell nucleus (Bestehorn et al, Molecular Cell 2025).

IL-1α and IL-1β: Why two is better than one

IL-1α and IL-1β are pro-inflammatory cytokines that use the same receptor and elicit same cellular responses. Why are both maintained in mammalian genomes? We were able to define essential and non-redundant functions of IL-1α and IL-1β in protection against bacterial infections: IL-1α drives pathways preventing tissue damage, hence tolerance, while IL-1β is essential for pathogen clearance, thus resistance. See our publication Eislmayr et al, Science Advances 2022.

Mediator kinases CDK8 & CDK19: Twin enzymes with non-twin roles in transcription regulation

The Mediator kinase is an enigmatic transcription regulator. Our recent study showed that the Mediator kinase controls Pol II pause release (Steinparzer et al, Molecular Cell 2019). Moreover, the Mediator kinases CDK8 and CDK19 (originally thought to be functionally redundant) fulfil mechanistically distinct functions and activate different gene sets in the interferon-induced anti-viral response.

mRNA decay sets the clock for neutrophil apoptosis

The lifespan of neutrophils co-determines the duration of immune responses. We showed that TTP-driven mRNA decay is a selective promoter of apoptosis of pathogen-engaged neutrophils: TTP subdues anti-apoptotic (Ebner et al., J Clin Invest 2017). Intriguingly, TTP deletion augments neutrophil response and blunts bacterial infection.

TTP atlas: a functionally annotated map of TTP binding sites in the macrophage transcriptome

The mRNA-destabilizing protein TTP is a key factor in elimination of cytokine mRNAs. By using PAR-iCLIP and mRNA stability assays we established the TTP Atlas, a nucleotide resolution map of functionally annotated TTP binding sites in the macrophage transcriptome (Sedlyarov et al., Mol Syst Biol 2016).

    Team

    Ronit Chakraborty
    PhD Student
       +43 1 4277 54627
    Room: 4.514

    Jeanne Fesselet
    PhD Student
       +43 1 4277 54626
    Room: 4.516

    Maurizio Forte
    PhD Student
       +43 1 4277 54626
    Room: 4.516

    Magdalena Klawatsch
    Master Student
       +43 1 4277 54625
    Room: 4.514

    Pavel Kovarik
    Group Leader
       +43 1 4277 54608
    Room: 4.615

    Lisa Neureuter
    Lab Technician
       +43 1 4277 54625
    Room: 4.514

    Adriana Valkova
    Master Student
       +43 1 4277 54626
    Room: 4.516

    Julius von Wirén
    PhD Student
       +43 1 4277 54627
    Room: 4.514

    Christina Zeiler
    PhD Student
       +43 1 4277 54626
    Room: 4.516

    Alumni

    Fiona Freyberger (TA)          

    Annika Bestehorn (PhD thesis)

    Kevin Doppelmayer (MSc thesis)     

    Fabian Thurner (MSc thesis)

    Morelli Luisa (MSc thesis)

    Anita Le Heron (postdoc)

    Lidia Silva (postdoc)

    Kevin Eislmayr (PhD thesis) 

    Martina Borroni (PhD thesis)

    Lucy Sneezum (PhD thesis) 

    Stefan Benke (postdoc)

    Helene Dworak (MSc thesis)

    Renata Kleinova (MSc thesis)

    Jakob Huemer (MSc thesis)

    Terezia Včelková (MSc thesis)

    Laura Wandruszka (MSc thesis)

    Uschi Damböck (MSc thesis)

    Masa Ivin (PhD thesis)         

    Iris Steinparzer (PhD thesis)

    Bastian Oppl (PhD thesis)

    Christina Mühlbacher/Fieber (PhD thesis)

    Virginia Castiglia (PhD thesis)          

    Florian Ebner (PhD thesis)

    Vitaly Sedlyarov (PhD thesis)           

    Marton Janos (PhD thesis)

    Thaddäus Pfaffenwimmer (MSc thesis)

    David Mairhofer (MSc thesis)

    Harald Hartweger (MSc thesis)

    Ivana Mikulic/Wiesauer (PhD thesis)

    Christian Machacek (MSc thesis)

    Joanna Bancerek (PhD thesis)

    Franz Kratochvill (PhD thesis)

    Josephine Grass (MSc thesis)

    Nina Gratz (PhD thesis)

    Irene Gattermeier (MSc thesis)

    Iwona Sadzak (PhD thesis)

    Barbara Schaljo (PhD thesis)

    Melanie Schiff (MSc thesis)

    Ines Sauer (PhD thesis)

    Selected Publications

    Cytoplasmic mRNA decay controlling inflammatory gene expression is determined by pre-mRNA fate decision.

    2025 Molecular cell
    PMID:  39862867

    Bestehorn Annika, von Wirén Julius, Zeiler Christina, Fesselet Jeanne, Didusch Sebastian, Forte Maurizio, Doppelmayer Kevin, Borroni Martina, Le Heron Anita, Scinicariello Sara, Chen WeiQiang, Baccarini Manuela, Pfanzagl Vera, Versteeg Gijs A, Hartl Markus, Kovarik Pavel

    Nonredundancy of IL-1α and IL-1β is defined by distinct regulation of tissues orchestrating resistance versus tolerance to infection.

    2022 Science advances;8(9):eabj7293.
    PMID:  35235356

    Eislmayr Kevin, Bestehorn Annika, Morelli Luisa, Borroni Martina, Vande Walle Lieselotte, Lamkanfi Mohamed, Kovarik Pavel

    Transcriptional Responses to IFN-γ Require Mediator Kinase-Dependent Pause Release and Mechanistically Distinct CDK8 and CDK19 Functions.

    2019 Molecular cell;76(3):485, 499.e8, 485-499.e8.
    PMID:  31495563

    Steinparzer Iris, Sedlyarov Vitaly, Rubin Jonathan D, Eislmayr Kevin, Galbraith Matthew D, Levandowski Cecilia B, Vcelkova Terezia, Sneezum Lucy, Wascher Florian, Amman Fabian, Kleinova Renata, Bender Heather, Andrysik Zdenek, Espinosa Joaquin M, Superti-Furga Giulio, Dowell Robin D, Taatjes Dylan J, Kovarik Pavel

    View all Publications of Group Kovarik

    Collaborations & Funding

    International and national network grants

    Doctoral college SMICH (Signaling Mechanisms in Cell Homeostasis)

    funded by the Austrian Research Fund FWF

    Marie Curie Doctoral Training Network INBIONET

    funded by European Commission MSCA

     

    Special research area (SFB) RNA-Regulation of the Transcriptome

    funded by the funded by the Austrian Research Fund FWF

     

    Infect-ERA HAPLOINFECT

    funded by the Austrian Research Fund FWF and European Commission FP7, project coordinator: Pavel Kovarik

      

    Research platform “Decoding mRNA decay in inflammation”

    funded by the University of Vienna, project coordinator: Pavel Kovarik

    Infect-ERA Innate immune responses to Streptococcus pyogenes

    funded by the Austrian Research Fund FWF and European Commission FP7; project coordinator: Pavel Kovarik

        

    Doctoral program (Initiativkolleg) Cell Nucleus

    funded by the University of Vienna, project coordinator: Pavel Kovarik

    EURODYNA Interferon-Induced Transcription and Nuclear Reorganization

    funded the Austrian Research Fund FWF and European Science Foundation; coordinator: Pavel Kovarik

     

         ESF

    Principle Investigator grants

    Nuclear licensing of cytoplasmic mRNA decay; funded by the Austrian Research Fund FWF

    Distinct functions of IL-1α versus IL-1β in host defense; funded by the Austrian Research Fund FWF

    Taming IL-1 signaling by mRNA decay; funded by the Austrian Research Fund FWF

    Transcription regulation by Mediator kinases CDK8 and CDK19; funded by the Austrian Research Fund FWF

    Regulation of STAT1 and cytokine responses by CDK8; funded by the Austrian Research Fund FWF

    Type I interferons in infection with Streptococcus pyogenes; funded by the Austrian Research Fund FWF

    Transcription cycle of Stat-1- regulated transcription; funded by the Austrian Research Fund FWF

    Innate immune responses to Streptococcus pyogenes; funded by the Austrian Research Fund FWF

    Integration of Interferon and Stress Signals; funded by the Austrian Research Fund FWF

    07
    Search on the site...

    office@maxperutzlabs.ac.at

    +43 1 4277 240 01


    Vienna BioCenter
    Dr.-Bohr-Gasse 9, 1030 Vienna