Research field: Molecular mechanisms of inflammation and immunity

Group leader: Prof. Dr. Rudi Beyaert

Tel:+32 9 33 13 770  -  Fax:+32 9 33 13 609
E-mail: Rudi.Beyaert.spam.detractor@dmbr.vib-UGentspam.corruptor.be

Research topic

The goal of our research is to understand the molecular mechanisms that control inflammation and immunity. We are focusing on specific intracellular signaling cascades, such as the nuclear factor-kappaB (NF-kB) pathway, which is activated in response to injury, infection, inflammation and other stressful conditions requiring rapid reprogramming of gene expression. Inappropriate NF-kB dependent gene expression is implicated in the pathogenesis of inflammatory diseases and cancer. We are using several molecular and biochemical approaches to elucidate the mechanisms that control NF-kB activation downstream of cytokine receptors (TNF, IL-1, IL-33) and immune receptors (TLRs, TCR). Using conditional gene targeting in the mouse we also study the role of key signaling molecules in mouse models of inflammatory diseases (multiple sclerosis, rheumatoid arthritis, asthma, Crohn’s disease), infectious diseases (Pseudomonas or Influenza lung infection), as well as cancer.

Specific research topics include:

1. Regulation of NF-kB and IRF signaling by protein-protein interactions and ubiquitination;
2. Function and regulation of the deubiquitinating protein A20;
3. Function and regulation of the paracaspase MALT1;
4. Cell death signaling in the central nervous system;
5. Modulation of innate immunity by the T3SS of Pseudomonas aeruginosa.

Area of expertise

• Signal transduction in inflammation and immunity
• Cytokine signaling (TNF, IL-1, IL-33)
• Toll-like receptor signaling
• NF-B and IRF signaling
• Protein-protein interactions
• (De)Ubiquitination
• Mouse models of inflammation
• Conditional gene targeting in the mouse
• Pseudomonas lung infection
  
  

Technology transfer potential

• Identification of therapeutic targets in autoimmune and infectious disease
• Development and validation of anti-inflammatory tools

Selected publications

1. Vereecke et al. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology.
   Trends Immunol. 30, 383-391, 2009.
2. Coornaert et al. T cell receptor stimulation induces MALT1 paracaspase mediated cleavage of the NF-kB inhibitor A20
   Nature Immunol. 9, 263-271, 2008.
3. Galle et al. The Pseudomonas aeruginosa Type III secretion system plays a dual role in the regulation of Caspase-1 mediated IL-1b maturation.
   J. Cell. Mol. Med. 12, 1767-1776, 2008.
4. Huang et al. ABINs inhibit EGF receptor mediated NF-kappaB activation and growth of EGF receptor-overexpressing tumour cells. Oncogene. 27, 6131-6140, 2008.
5. Maelfait et al. Stimulation of Toll-like receptor 3 and 4 induces Interleukin-1β maturation by Caspase-8. J. Exp. Med. 205, 1967-1973, 2008.
6. Wagner et al. Ubiquitin binding mediates the NF-kB inhibitory potential of ABIN proteins
   Oncogene. 27, 3739-3745, 2008.