Edward Harhaj, PhD

The Harhaj laboratory focuses on the negative regulation of inflammatory signaling pathways and inflammation. Autophagy is a highly conserved lysosomal degradation pathway that removes unwanted or damaged cellular components such as protein aggregates, damaged organelles, and pathogens. A major focus of the lab is on TAX1BP1, a selective autophagy receptor that recruits specific cargo to autophagosomes for targeted degradation. TAX1BP1 has been shown to inhibit Toll-like receptor 3/4 (TLR3/4) signaling by targeting the adaptor TRIF for degradation. We have previously demonstrated that TAX1BP1 inhibits NF-kB signaling and are currently investigating the mechanisms by which TAX1BP1 restricts the activation of innate and inflammatory signaling pathways including RIG-I-like receptor (RLR) RNA sensing, cGAS-STING DNA sensing and NLRP3 inflammasome pathways. Our recent study showed that TAX1BP1 targets MAVS aggregates for degradation to inhibit RLR signaling, and phosphorylation of TAX1BP1 is critical for its aggrephagy function. We have generated TAX1BP1 conditional knockout mice and are examining tissue-specific functions of TAX1BP1 in regulating inflammation and inflammatory diseases. Our overarching hypothesis is that TAX1BP1 is a critical negative regulator of inflammation that safeguards immune homeostasis.