Libert Unit - Mouse Genetics in Inflammation

Research field: Regulation of inflammation, infection and aging

Group leader: Prof. Dr. Claude Libert

Tel:+32 9 33 13 700  -  Fax:+32 9 221 76 73
E-mail: Claude.Libert.spam.detractor@irc.vib-UGentspam.corruptor.be

Research topic

The main goal of our research is to contribute to the understanding of the molecular mechanisms that are involved in the progression of sepsis. Sepsis is a deadly disease that is initiated by a (bacterial) infection and leads to a severe host response. It hits 30 million people yearly, 8 million of which die (3 million children). The savage, acute and complex nature of sepsis has caused much confusion as to the most relevant molecular mechanisms involved. Since many clinical trials for sepsis have failed, the classical belief that sepsis is primarily inflammatory in nature is under pressure. In our group, we focus our attention on metabolic reprogramming in sepsis, which we think follows a pattern that is compatible with an extremely acute starvation response, but which fails due to the inhibition of the function of several important transcription factors, such as the Glucocorticoid Receptor and PPAR. The molecular pathways that undermine these factors form a central theme in our research.

Next to this metabolic project, we are also interested in the control of host-pathogen interplay between microbes of the gut and the Paneth cells in the ileum. This interaction is important in defining the composition of these microbes, as well as the sensitivity of intestinal cells for inflammation and cell death. We are focusing on the interaction between bacteria and Paneth cells, and the role of interferons in this interplay and the impact of zinc and other nutrients on this axis.

Finally, because we are applying mice as model animals, we are interested in the details of the mouse genome and which naturally occurring alleles of protein-coding genes and micro RNA genes are available in the 40 dee- sequenced mouse strains and the role that these variant alleles play in phenotypes of interest in the mouse strains.

 

Area of expertise

  • Cytokine biology
  • Sepsis models in mice
  • Metabolism
  • Liver biology
  • Nuclear receptors
  • Generation of mouse mutants
  • Mapping and cloning traits in mice
  • Genomics and transcriptomics


Fluorescent staining of MMP7 and lysosyme
located in the Paneth cells of the ileum

Selected publications

  1. Dendoncker K et al. TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile.
    Proc Natl Acad Sci USA., 116, 12942-12951, 2019.
  2. Ballegeer M et al. Glucocorticoid receptor dimers control intestinal STAT1 and TNF-induced inflammation in mice.
    J Clin Invest. 128, 3265-3279, 2018.
  3. Timmermans S et al. Complete overview of protein-inactivating sequence variations in 36 sequenced mouse inbred strains.
    Proc Natl Acad Sci USA. 114, 9158-9163, 2017.
  4. Puimège L et al. Glucocorticoid-induced microRNA-511 protects against TNF by down-regulating TNFR1.
    EMBO Molecular Medicine, 7, 1004-17, 2015.
  5. Van Hauwermeiren F et al. Safe TNF-based antitumor therapy following p55TNFR reduction in intestinal epithelium.
    Journal of Clinical Investigation, 123, 2590-603, 2013.

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