Van der Veen lab - Nucleic Acid Immunity

The innate immune system is activated upon infection with bacteria, fungi, and viruses. All nucleated cells are equipped with innate immune receptors, with which they screen their environment for signs of an ongoing infection. When they detect an infection, these receptors initiate defense pathways to destroy the pathogen. In the case of a virus infection, nucleic acid sensors detect the presence of viral DNA or RNA in the infected cells. Activation of these sensors subsequently leads to an antiviral type I interferon response.

In some cases, nucleic acid sensors are accidentally activated by one’s own molecules (in the absence of a viral infection) leading to unwanted type I inteferon production and sterile inflammation. This happens in inherited autoinflammatory disorders (known as type I interferonopathies) and complex autoimmune diseases. A sterile inflammatory response is also a hallmark of the tumor microenvironment and can impact on immune responses against a tumor.

The overarching goal of our research is to understand how cells maintain a balanced type I interferon response to ensure effective antimicrobial defense while avoiding sterile inflammation. By studying the molecular mechanisms that underly nucleic acid sensing, we aim to identify new targets for therapeutic intervention in autoinflammatory conditions and to inspire strategies to promote immunosurveillance in cancer.

The focus of our research is to understand how precisely type I interferons are induced in different disease contexts. What type of endogenous RNA molecules activate RNA sensors? What mechanisms do cells have in place to prevent this? And what happens if these mechanisms fail? We are using novel methods, such as iCLIP (individual-nucleotide UV crosslinking and immunoprecipitation) and CRISPR/Cas9, to understand the molecular basis of self/non-self recognition by the nucleic acid sensors of the innate immune system. Ultimately, this work will allow us to steer sterile inflammatory responses into a certain direction and to use it to our own advantage.