Beyaert Unit - Molecular Signal Transduction in Inflammation

Research field: Molecular mechanisms of inflammation and immunity

Group leader: Prof. Dr. Rudi Beyaert

Tel:+32 9 33 13 770  -  Fax:+32 9 221 76 73
E-mail: Rudi.Beyaert.spam.detractor@irc.vib-UGentspam.corruptor.be

Research topic

Our research is situated at the borderline between molecular biology and medicine. We are interested in the molecular mechanisms that control initiation, progression and resolution of inflammation and immunity. Further insight into these molecular mechanisms raises the prospect for better understanding and rational design of therapeutics for several diseases, including autoimmunity, allergy and cancer. In our research we make use a variety of biochemical, molecular and cellular approaches combined with mouse gene targeting and mouse models of human disease (e.g. multiple sclerosis, rheumatoid arthritis, Crohn’s disease, psoriasis, sepsis).

More specifically we are studying major intracellular signaling pathways (such as NF-κB signaling) that control gene expression in response to specific cytokine receptors (TNF, IL-1, IL-33), pattern recognition receptors (TLR4), and T cell antigen receptors. We have a particular interest in the role of protein-protein interactions and posttranslational modifications such as protein ubiquitination and phosphorylation. Our lab has made a significant contribution to the understanding of the mechanism of action and the physiological significance of the NF-kB inhibitory protein A20 (=TNFAIP3) in multiple cell types and diseases including rheumatoid arthritis and colitis. In addition, we discovered that the paracaspase MALT1, which is pivotal in antigen receptor-mediated lymphocyte activation and lymphomagenesis, has a unique proteolytic activity. This finding is now being validated and translated into therapeutics for human disease in collaboration with the pharmaceutical industry.

In collaboration with experts within and outside of IRC we are pursuing to study the molecular mechanisms that mediate and regulate the activity of A20, MALT1 and several other newly identified signaling proteins in the context of innate and adaptive immunity. We also exploit our knowledge and expertise in signaling to identify key molecules affecting phagosome function and the intracellular fate of antigens. Finally, based on innovative protein engineering approaches our research group is also developing novel biological tools that allow to interfere with the function of different cytokines and to treat immune-system related disease.

Area of expertise

  • Molecular signaling in inflammation and immunity
  • Protein-protein interactions, phosphorylation and ubiquitination
  • Cytokines, Toll-like receptor and T cell receptor signal transduction
  • NF-kappaB signaling
  • Mouse gene targeting and human disease models

Technology transfer potential

 

  • Novel therapeutic targets in inflammation and cancer (e.g. MALT1)
  • Novel immunomodulatory products (e.g. IL-33 trap)

 


Selected publications

  1. Afonina I et al. Limiting inflammation-the negative regulation of NF-kappaB and the NLRP3 inflammasome.
    Nature Immunology. 2017. 18, 861-869.

  2. Afonina I et al. The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes.
    EMBO Reports. 2016. 17, 914-27.

  3. Alloatti A et al. Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens.
    Immunity. 2015. 43, 1087-100.

  4. Vereecke L et al. A20 controls intestinal homeostasis through cell-specific activities.
    Nature Communications. 2014. 5, 5103.
  5. Verhelst K et al. A20 inhibits LUBAC-mediated NF-kappaB activation by binding linear polyubiquitin chains via its zinc finger 7. 
    EMBO Journal. 2012. 31, 3845-55.

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