Bertrand team: Signal transduction in Cell death and Inflammation

Research Field: Molecular regulation of innate immune and cell death pathways

Team leader: Prof. Dr. Mathieu Bertrand

Tel: +32 9 33 13 720 - Fax: +32 9 221 76 73
Email: Mathieu.Bertrand.spam.detractor@irc.vib-UGentspam.corruptor.be

Research topic

Our research team focuses on the study of the molecular mechanisms regulating cell death and inflammation, two interconnected cellular processes. Inflammation, the first response of the immune system to infection or tissue injury, is of crucial importance to protect the human body against these insults. Nevertheless, inflammation needs tight regulation as it can turn into a maladaptive response at the origin of various human diseases (such as septic shock, inflammatory bowel disease, psoriasis, cancer, ) when not properly controlled. On the other hand, cell death is an essential cellular process during development and for homeostasis, and is also known to drive inflammation during sterile injury or to amplify inflammation during infection. Gaining a better understanding of the molecular mechanisms that regulate cell death, the type of cell death modality induced, and how dead cells drive inflammation therefore has important implications for our understanding and treatment of inflammatory diseases.

Cell death and innate immunity are ancient evolutionary conserved processes that use a great number of related molecular effectors and parallel signal transduction mechanisms. In our research group, we study regulation of the signalling pathways activated downstream of innate immune Pattern Recognition Receptors (PRRs), and members of the Tumor Necrosis Factor Receptor (TNFR) family. We aim at understanding the molecular nature of the checkpoints that regulate the different cellular outcomes, namely cell survival, cell death (mainly apoptosis and necroptosis) and inflammation. We have a particular interest in the receptor interacting protein kinases (RIPKs) and in their regulation by post-translational modifications. Our studies are conducted at the biochemical, cellular and in vivo levels.

Schematic representation of signaling downstream of the NOD1/2 innate immune receptors. Vandenabeele P and Bertrand MJ, Nature Reviews Immunology, 2012.
Cell death checkpoints in TNFR1 signaling. Ting A and Bertrand MJM. Trends Immunol. 2016. Click to enlarge.

Areas of expertise

  • Signal transduction
  • Receptor signaling complexes, protein-protein interactions
  • Post-translational modifications (phosphorylation, ubiquitylation)
  • Cell death (apoptosis, necroptosis)
  • RIPK1/3, Caspases, cIAP1/2, TRAFs, NF-kB, MAPKs

Technology transfer potential

Identification of new therapeutic targets for the treatment of cell death and inflammation related diseases

Recent publications

  1. Dondelinger Y, Delanghe T et al. MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. 
    Nature Cell Biology, 2017. In press.
  2. Rojas-Rivera D et al. When PERK inhibitors turn out to be new potent RIPK1 inhibitors: critical issues on the specificity and use of GSK2606414 and GSK2656157.
    Cell Death and Differentiation, 24, 1100-1110, 2017.
  3. Ting A and Bertrand MJM. More to life than NF-kB in TNFR1 signaling.
    Trends in Immunology, 37(8):535-45, 2016.
  4. Aguileta M et al. A siRNA screen reveals the pro-survival effect of protein kinase A (PKA) activation in conditions of unresolved endoplasmic reticulum stress.
    Cell Death and Differentiation, 23, 1670-80, 2016.
  5. Dondelinger Y et al. NF-kB-independent role of IKKa/IKKb in preventing RIPK1 kinase-dependent apoptotic and necroptotic cell death during TNF signaling.
    Molecular Cell, 60, 63-76, 2015.

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