Research topicThe goal of our research is to understand the molecular mechanisms that control inflammation and immunity. The NF-κB signaling pathway plays a prominent role in the development and function of the immune system and, not surprisingly, when dysregulated, contributes to the pathophysiology of inflammatory disease and cancer. We mainly focus on the molecular mechanisms that fine-tune NF-κB signaling in response to cytokines (TNF, IL-1, IL-33), T cell receptors, and pattern recognition receptors (TLR). In particular we are interested in NF-κB regulation by the ubiquitin-editing protein A20 and the paracaspase MALT1. Our studies utilize biochemical, cell biological, as well as whole animal approaches involving mouse gene targeting and specific mouse models of inflammatory and infectious diseases.
Specific research topics include:
- Regulation and mechanism of action of the anti-inflammatory protein A20;
- Pathophysiological role of A20 in colitis, hepatitis, diabetes, and neuroinflammation (subgroup van Loo);
- Regulation and mechanism of action of the paracaspase MALT1;
- Role of MALT1 in autoimmunity;
- Characterization of IL-33 as a therapeutic target;
- Pathophysiological role of ER stress signaling (subgroup van Loo);
- Characterization of selective autophagy receptors.
Area of expertise
- Signal transduction in immunity and inflammation;
- Cytokines and Toll-like receptors;
- NF-κB signaling;
- Protein-protein interactions and ubiquitination;
- Mouse gene targeting and disease models.
Technology transfer potential
- Immunomodulatory products;
- Therapeutic targets in autoimmunity;
- Novel mouse models for inflammatory diseases.
- Verhelst et al. A20 inhibits LUBAC-mediated NF-kB activation by binding linear polyubiquitin chains via its zinc finger 7
EMBO J 31, 3845-55, 2012
- Maelfait et al. A20 (Tnfaip3) deficiency in myeloid cells protects against Influenza A virus infection
PLoS Pathogens 8, e1002570, 2012
- Matmati et al. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis
Nature Genet 43, 908-12, 2011
- Staal et al. T-cell receptor-induced JNK activation requires proteolytic inactivation of CYLD by MALT1
EMBO J. 30, 1742-52, 2011
- Vereecke et al. Enterocyte specific A20/TNFAIP3 deficiency sensitizes to TNF toxicity and experimental colitis
J Exp Med 207, 1513-1523, 2010
- Coornaert et al. T cell receptor stimulation induces MALT1 paracaspase mediated cleavage of the NF-B inhibitor A20
Nature Immunol 9, 263-271, 2008.