Host defence against infection critically depends on the innate immune system. Invading pathogens are sensed by innate immune receptors, such as the RIG-I-like receptors (RLRs) that survey the cytosol for the presence of viral RNA structures. When activated, RLR signalling triggers the production of type I interferons that drive the expression of antiviral genes. In addition, type I interferons effectively clear infected cells by suppressing cell proliferation and sensitizing cells to apoptosis. This can, however, lead to severe immunopathology when interferons are produced in excess or for prolonged times. To avoid this, cells have evolved mechanisms that tightly regulate RLR activity. Both the induction and termination of RLR signalling are heavily regulated through dynamic post-translational modifications, including ubiquitination. My research aims to decipher how the ubiquitin machinery impacts on RLR sensing and how this aids in regulating antiviral immune responses.
I studied Life Science and Technology at the Technical University Delft and Leiden University, during which I performed a Master’s research project in the department of Cell and Chemical Biology (LUMC) in the group of Dr. Maaike Ressing and Prof. Rob Hoeben. I was awarded a personal grant by the Dutch Research Council (NWO Graduate programme) to pursue a PhD in the field of innate immune signalling and I continued as a PhD student in the same group. My PhD research focused on the cellular mechanisms that drive antiviral transcriptional programs following Toll-like receptor activation. In August 2020, I joined the group of Dr. Annemarthe van der Veen as a postdoctoral researcher.
RNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency
Stok JE*, Oosenbrug T*, Ter Haar LR, Gravekamp D, Bromley CP, Zelenay S, Reis e Sousa C, Van der Veen AG
The EMBO Journal, Feb 14 2022, DOI: 10.15252/embj.2021109760
Conditionally Controlling Human TLR2 Activity via Trans-Cyclooctene Caged Ligands
Michel J van de Graaff, Timo Oosenbrug, Mikkel H S Marqvorsen, Clarissa R Nascimento, Mark A R de Geus, Bénédicte Manoury, Maaike E Ressing, Sander I van Kasteren
Bioconjug Chem . 2020 Jun 17;31(6):1685-1692
Chemical Tools for Studying TLR Signaling Dynamics
Timo Oosenbrug, Michel J van de Graaff, Maaike E Ressing, Sander I van Kasteren
Cell Chem Biol. 2017 Jul 20;24(7): 801-812