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Andy Wullaert

  • Research interest  (University of Antwerp):My research group investigates the function of cytosolic protein complexes termed inflammasomes that play important roles in immune responses. Inflammasome activation happens through a sensor protein that senses the trigger, after which a protease termed caspase-1 executes inflammasome functions. Both pathogens and host-derived danger and stress signals can trigger caspase-1 activity of inflammasomes, which then cleaves its substrates. These substrates include Gasdermin D, of which the N-terminal fragment then triggers a lytic form of cell death termed pyroptosis. This inflammasome-induced cell death mode is accompanied by the release of the IL-1β and IL-18 pro-inflammatory cytokines, both of which are maturated by caspase-1 activity, as well as several danger-associated molecular patterns that together mount an efficient inflammatory response. Among the widespread impact of inflammasome signaling on human health, our research focuses on the role of inflammasome signaling and pyroptosis in infectious diseases and auto-inflammatory diseases (AIDs). During infections, inflammasome responses mainly contribute to host defense. Conversely, individuals with gain-of-function mutations in genes encoding inflammasome components suffer from AIDs. For the latter we have several genetic mouse models at our disposal in which inflammasomes are hyperactivated. In the context of infectious diseases, we are investigating murine inflammasome and pyroptosis responses to several viral, bacterial and fungal pathogens. By studying these auto-inflammation and infection mouse models we aim to elucidate the cellular and molecular mechanisms how inflammasome-induced pyroptosis drives auto-inflammatory diseases as well as host defense against pathogens.
  • Keywords  (University of Antwerp):CYTOKINES, AUTO-INFLAMMATIE, INFLAMMATION, INNATE IMMUNITY, CELL FATE, INFLAMMASOME, INFECTIONS, Biomedical sciences (incl. biochemistry)
  • Keywords  (Ghent University):inflammation
  • Disciplines  (University of Antwerp):Inflammation, Innate immunity, Infectious diseases, Cell death , Cell signalling, Posttranslational modifications
  • Disciplines  (Ghent University):Gastro-enterology, Inflammation, Innate immunity, Infectious diseases, Cell death , Microbiome
  • Research techniques  (University of Antwerp):Our expertise lies in the generation and use of genetic mouse models in innate immunity research. We have several genetic mouse models at our disposal with full-body or cell type specific deletion of genes, or with constitutive or inducible expression of mutant genes encoding for proteins involved in inflammasome and innate immune responses. In the context of innate immunity we have expertise in immunological analysis of in vivo myeloid immune responses (flow cytometry, cell sorting, histology, immune histochemistry, cytokine analyses) during inflammation and infection. Ex vivo, we have expertise in primary cell isolation and culture from mice (bone marrow derived macrophages, monocytes, neutrophils; peritoneal cells; intestinal epithelial organoids). In addition we have expertise in using primary human cells (PBMCs, monocytes, cord blood derived hematopoietic stem cells). Using human hematopoietic stem cells we have expertise in the generation of humanised mice. Using in vivo and ex vivo samples we have expertise in molecular analyses of inflammasome activation (western blot analyses, imaging) as well as analyses of cell death (real-time imaging, flow cytometry, western blot).
  • Users of research expertise  (University of Antwerp):Our expertise in the analysis of innate immune responses and in particular inflammasome signaling can be useful for all researchers interested in inflammation, infection and immune responses at large. In addition to immune responses, inflammasomes are involved also in in neurodegenerative diseases. For instance, Alzheimer’s disease associated β-amyloid crystals are well-established inflammasome triggers. In addition, inflammasome activities also determine host metabolism, for instance by their cholesterol-induced activation while ketones have inflammasome inhibitory effects. In cancer, inflammasome inflammatory effects in the tumor micro-environment can promote tumorigenesis, while some chemotherapeutics were shown to induce tumor cell pyroptosis, which might enhance anti-tumor immune responses. Taken together, inflammasomes are protein complexes that are regulated by a very diverse set of molecules and thereby impact on a wide variety of human diseases. Therefore, our inflammasome expertise can be of wide interest to biomedical researchers.