Molecular Signal Transduction in Inflammation

Molecular mechanisms of inflammation and immunity

A major research topic is MALT1 paracaspase signaling, which mediates NF-κB activation and modulates the threshold for activation of several immune and non-immune cells in response to a rapidly growing number of stimuli. Our original discovery that MALT1 holds a unique proteolytic activity has led to a conceptual breakthrough and the therapeutic targeting of MALT1 in autoimmunity and cancer. On the other hand, genetic defects in the MALT1 pathway are associated with human immunodeficiency syndromes, autoinflammation and cancer. Moreover, MALT1 signaling is now known to play roles that extend well beyond NF-κB. This biological breadth of MALT1 signaling opens up several research opportunities. We are studying the functional role of specific MALT1 substrates and MALT1 interacting proteins in T cells, as well as the cell type-specific interaction of MALT1 with CARD-CC family proteins, with a particular interest in the role of CARD14 in epithelial cells in the context of skin and gut-related disease. We are also investigating novel therapeutic targeting approaches of MALT1 signaling.

Our lab is also involved in a number of other multidisciplinary projects that are imbedded in well-established research consortia with other academic labs, clinicians, and the biotech sector, including the bio-engineering and use of innovative biologics targeting specific cytokines, nutritional applications of phytohormones in inflammatory disease, as well as the characterization of novel candidate susceptibility genes in IBD or immunodeficiency syndromes.

Areas of Expertise

• Intracellular signaling (protein-protein interactions, phosphorylation, ubiquitination)
• T cell and epithelial cell biology
• Cytokine biology
• Innate and adaptive immunity
• Inflammatory bowel disease and psoriasis models in mice

Technology Transfer Potential

• Mouse engineering and modeling of human disease (IBD, psoriasis, immunodeficiency)
• Therapeutic targeting of cytokines, cytokine receptors and intracellular signaling proteins (small compound inhibitors, protein engineering, nanobodies, …)
• Assay development
• Nutritional applications in inflammatory or metabolic disease

Selected publications

• Holgado, A. et al. A20 is a master switch of IL-33 signaling in macrophages and determines IL-33-induced lung immunity. J Allergy Clin Immunol 152, 244-256 (2023). Visit ➚
• Demeyer, A. et al. Long-Term MALT1 Inhibition in Adult Mice Without Severe Systemic Autoimmunity. iScience 23, 101557 (2020). Visit ➚
• Van Nuffel, E. et al. MALT1 targeting suppresses CARD14-induced psoriatic dermatitis in mice. EMBO Rep 21, e49237 (2020). Visit ➚
• 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). Visit ➚
• Coornaert, B. et al. T cell antigen receptor stimulation induces MALT1 paracaspase mediated cleavage of A20. Nat. Immunol. 9, 263-271 (2008). Visit ➚

Bibliography

• Full bibliography Visit ➚

External links

• VIB Grand Challenges Program - Understanding primary immune deficiencies Visit ➚