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

Dysregulated immune signaling may lead to the development of chronic autoimmune diseases and cancer. The Beyaert group studies the complex role of key signaling molecules in the fine-tuning and self-limiting nature of major signaling pathways that control gene expression in response to inflammatory triggers, further insights of which raises the prospect for better understanding and rational design of therapeutics for several diseases, including autoimmunity, allergy and cancer. The researchers use a variety of omics-based molecular approaches combined with cellular models, mouse gene targeting and mouse models of human disease.

A major research interest of the group is the function and regulation of MALT1. The groupís discovery that MALT1 holds a unique proteolytic activity in lymphocytes has led to a conceptual breakthrough and initiated a strong interest worldwide in the therapeutic targeting of MALT in the context of autoimmunity and certain MALT1-dependent lymphoma cancers. Besides studying the complex role of MALT1 in T cell receptor signaling and T cell homeostasis, the Beyaert lab has taken another great leap forward by also studying the role of MALT1 signalosomes in skin and gut epithelial cells in the context of psoriasis and colitis, respectively.

A second research line focuses on IL-33, a cytokine that is well known for its key role in allergy. Here, the team is studying not only the molecular mechanisms that regulate IL-33 activity, but also uses innovative protein engineering approaches to develop novel IL-33 targeting biologics as new tools to treat allergic and other diseases in which IL-33 plays an important role.

Recently, a third and completely novel research line has been initiated, which aims to investigate the biosynthesis and anti-inflammatory function of two metabolites, abscisic acid and salicylic acid, as novel endogenous immune regulators in mammals.

Finally, Rudi Beyaert also coordinates the recently launched VIB Grand Challenge Program on Primary Immune Deficiency, which is a multidisciplinary translational initiative that addresses the urgent need for molecular diagnostic tools to better identify and classify PID patients and guide therapeutic decisions in the clinic.

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. Gilis E et al. MALT1-deletion in T-cells protects against the development of auto-immune arthritis, but causes spontaneous osteoporosis.
    Arthritis Rheumatol, in press, 2019.
  2. Holgado A et al. IL-33trap is a novel IL-33 neutralizing biologic that inhibits allergic airway inflammation.
    J Allergy Clin Immunol, 144, 204-215, 2019.
  3. Afonina I et al. Limiting inflammation-the negative regulation of NF-kappaB and the NLRP3 inflammasome.
    Nature Immunology, 18, 861-869, 2017.
  4. Afonina I et al. The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes.
    EMBO Reports, 17, 914-27, 2016.
  5. Alloatti A et al. Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens.
    Immunity, 43, 1087-100, 2015.

VIB Grand Challenges Program

This research is part of the VIB Grand Challenges Program. More information, click here.

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