Signaling and gene expression in inflammation

The Question

Our research aims at understanding of how immune homeostasis is maintained and how a robust but not exaggerated immune response is accomplished. Defense against infectious agents and damaging cues requires efficient activation of inflammatory response and timely re-establishment of immune homeostasis once the hostile microbial or sterile cues have been eliminated. Unproductive responses result in infectious disease whereas failures in homeostatic processes cause tissue damage and prevent healing. Thus, inflammatory response needs to be strong but quantitatively and timely restricted. Although many of the inflammation-promoting and –controlling processes are known, the basic question of how these processes are coordinated in the context of balanced tissue-protective immune responses remains poorly understood. We study the molecular wiring of robust yet controlled inflammation at the level of transcription, mRNA decay and signaling.

The Approach

Not Too Little, Not Too Much, Just Right: We investigate immune homeostasis and balanced immune responses in 3 areas:

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

2) Mediator kinases in transcriptional responses to cytokines. We investigate how Mediator kinases - enigmatic positive and negative general transcription regulators – tune responses to cytokines. Approach: biochemistry, proteomics and genome-wide assays (GRO-Seq, PRO-Seq, ChIP-Seq etc.).

3) Cytokine signaling in resistance and resilience to infections. Using animal models of infection combined with metabolomics, transcriptomics and cell biology we investigate the key question of how cytokines regulate both elimination of pathogens (resistance) and tissue protection (resilience).