Olivia Majer, PhD

I am an immunologist interested in how immune responses are regulated to prevent harmful reactions against own body tissue. My lab studies this through the lens of innate immune receptors, focusing on how their precise positioning within the cell is essential to avoiding autoreactive responses. By examining the sorting behavior and subcellular environments in which these receptors operate, we aim to uncover new mechanisms that control their activity and prevent disease.

During my PhD, I investigated Type I Interferon (IFN-I) signaling during fungal infections, identifying TLR7 as a critical senor of fungal RNA. This pathway triggered IFN-I responses that promoted immunopathology in vivo. Midway through my PhD, I joined Jon Kagan’s Lab at Harvard Medical School as a visiting student, a formative experience that sparked my passion for mechanistic biology, particularly using cell biology approaches to address immunological questions.

For my postdoctoral work in Greg Barton’s lab at UC Berkeley, I studied how the trafficking of nucleic acid-sensing TLRs enables discrimination between self and non-self. My work focused on Unc93b1, the trafficking chaperone for these TLRs. Through a large-scale mutagenesis screen, we established Unc93b1 as a central regulator of TLR activity and crucial checkpoint to prevent autoimmune disease in mice. The work has yielded unprecedented insights into the pathogenesis of systemic lupus erythematosus (SLE), and established for the first time the importance of receptor trafficking and localization as critical regulatory layer to maintain immune homeostasis.

Recognizing the limitations of existing tools for visualizing intracellular TLR trafficking, I trained in super-resolution microscopy in Helge Ewers’ lab in Berlin. In 2020, I established my own research group at the Max Planck Institute for Infection Biology, applying advanced imaging approaches such as structured illumination microscopy to study TLR biology.

Our recent work has identified the first human Unc93b1 mutations in pediatric patients with SLE. We found that one of these mutations disrupts the interaction between Unc93b1and the endosomal sorting complex BORC, impairing the degradation of TLR7. This leads to receptor accumulation and heightened responses to self-RNA. Importantly, our findings demonstrate that single mutations in innate immune pathways can be sufficient to trigger SLE, a disease traditionally considered an adaptive immune disorder due to its hallmark autoantibodies.

In 2025 my lab moved to the Cincinnati Children’s, where we continue to investigate how organelle biology and protein trafficking shape innate immunity, aiming to provide fundamental insights into disease mechanisms and inform targeted therapeutic strategies.