Prof. Mathieu Bertrand, VIB, Ghent University, lectures on Regulation of TNF cytotoxicity by unconventional forms of autophagy

UIPS International Seminar Programme

Lecturer: Prof. dr. Mathieu JM Bertrand, VIB Center for Inflammation Research, Department of Biomedical Molecular Biology, Ghent University, Ghent Belgium
Title: Regulation of TNF cytotoxicity by unconventional forms of autophagy

Monday 8 June 2026 from 13.00-14.00, David de Wied Building 1.22
Hosted by dr. Kelly Stecker, k.e.stecker@uu.nl 

Short Bio:

Mathieu JM Bertrand studied bioengineering at the University of Louvain (UCL), and obtained his PhD on the functional characterisation of the MAGE genes in the lab of Prof. DeBacker at the LudwigInstitute for Cancer Research (LICR) and University of Namur. His first postdoctoral training was at the lab of Prof. Barker at McGill University, studying regulation of innate immune signalling by ubiquitylation. He later joined the lab of Prof. Vandenabeele at the Vlaams Instituut voor Biotechnologie (VIB) and Ghent University for a second postdoc, focusing on post-translational modification driven cell death regulation. In 2011, he was appointed with a professor position at Ghent University, and since then he leads a research team at the VIB-UGent Center for Inflammation Research (IRC). Research in his lab aims at characterising the interplay between cell death and inflammation, and at defining the role of cell death in the context of infection and inflammatory pathologies. The lab has expertise in the investigation and characterisation of the molecular mechanisms regulating cell survival/death and inflammatory responses downstream of TNF receptor superfamily members and pattern recognition receptors. Recently, the lab developed strong interest in the role of autophagy in the various aspects of the inflammatory response.

Bertrand research group Bibliography: https://www.irc.ugent.be/groups/bertrand-team (The VIB-UGent Center for Inflammation Research). 

Abstract: 

Tumor necrosis factor (TNF) is a central cytokine in inflammatory responses, and TNF-neutralizing biologics rank among the most successful therapies for chronic inflammatory diseases. Binding of TNF to TNFR1 induces the assembly of a membrane-bound signaling platform, known as TNFR1 Complex I, which promotes pro-inflammatory gene expression through activation of the MAPK and NF-κB pathways. In addition, TNFR1 sensing of TNF indirectly promotes and exacerbates inflammation by triggering cell death via the formation of a secondary, receptor-dissociated cytosolic complex termed TNFR1 Complex II.
While TNF-mediated cell death can be beneficial in the context of infection, uncontrolled or excessive TNF-induced cytotoxicity is highly detrimental and underlies a wide range of inflammatory pathologies. To counteract this, multiple protective mechanisms - collectively referred to as cell death checkpoints - operate to restrain TNF cytotoxicity and safeguard tissue homeostasis.
Our laboratory recently identified a novel cell death checkpoint within the TNF pathway that relies on the lysosomal turnover of TNFR1 Complex II through an unconventional form of macro-autophagy. We have now discovered that the protective function of this atypical macro-autophagy extends beyond TNFR1 Complex II degradation, revealing an unexpected additional pathologic alarm of the TNF response. Furthermore, we identify endosomal micro-autophagy (eMI) – mediated detoxification of TNFR1 Complex II as a parallel, non-redundant cell death checkpoint in the TNF signaling cascade.