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 mainly focus on the nuclear factor-kappaB (NF-kB) signaling 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 generate fundamental knowledge on the biology of a limited subset of molecules that control NF-κB signaling downstream of key cytokine (e.g. TNF, IL-1, IL-33) and immune receptors (e.g. TLR, TCR). The pathophysiological role of our in vitro findings is validated in appropriate disease models (e.g. multiple sclerosis, rheumatoid arthritis, Crohn’s disease, Influenza infection, inflammation associated cancer).

Specific research topics include:

1. Regulation of NF-kB and IRF signaling by ubiquitin binding proteins;
2. Molecular regulation of the ubiquitin-editing protein A20;
3. Study of the pathophysiological role of A20 using tissue-specific gene targeting and mouse models of disease;
4. Biological function, regulation, and novel substrates of paracaspase MALT1;
5. Cross-talk between TCR and glutamate receptor signaling;
6. ER stress and NF-κB signaling;
7. NF-κB signaling and selective autophagy.

Area of expertise

• Inflammation and innate immunity;
• Cytokines (TNF, IL-1, IL-33);
• Toll-like receptors;
• NF-kB and IRF signaling;
• Protein-protein interactions;
• (De)Ubiquitination;
• Mouse models of infection, inflammation, and inflammation associated cancer;
• Conditional gene targeting in the mouse.

Technology transfer potential

• Immunomodulatory products;
• Therapeutic targets in autoimmunity;
• Novel mouse models for inflammatory diseases.

Selected publications

1. Vereecke et al. Enterocyte specific A20/TNFAIP3 deficiency sensitizes to TNF toxicity and experimental colitis
   J Exp Med 207, 1513-1523, 2010
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. 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.
4. Galle et al. The Pseudomonas aeruginosa Type III secretion system plays a dual role in the regulation of Caspase-1 mediated IL-1β maturation.
   J Cell Mol Med 12, 1767-1776, 2008.
5. Huang et al. ABINs inhibit EGF receptor mediated NF-kB activation and growth of EGF receptor-overexpressing tumour cells.
   Oncogene 27, 6131-6140, 2008.
6. Wagner et al. Ubiquitin binding mediates the NF-kB inhibitory potential of ABIN proteins
   Oncogene 27, 3739-3745, 2008.