Ongoing Projects
Characterizing the developmental role of the tau protein
During my postdoctoral fellowship with Dr. John Crary at Mount Sinai, I characterized tau phosphorylation and splicing in the developing human brain. In my laboratory, I then went on to determine the timing of tau expression in the developing human brain and show that loss of tau in human neurons causes abnormal dendritogenesis, likely due to the loss of trophic NMDAR signaling (Fiock et al., 2020). These remarkable findings have led to the pending R01 award from NIH/NINDS, which received a 3rd percentile score and cemented our position as experts in working with human brain tissue and stem-cell-derived neuronal and astrocytic models. I have also collaborated closely with other leading investigators at the University of Iowa, including Drs. Joseph Glykys, Banu Gumusoglu, and Hanna Stevens to build an extensive collaborative neurodevelopment research network.
Identifying mechanisms of tau resilience in the developing brain
My laboratory carried out the first systematic comparison of the tau interactome between human fetal, adult, and Alzheimer’s disease brains, showing previously undescribed developmental shifts in the tau interactome (Betters et al., 2023). Building on this, we used stem-cell-derived neurons and astrocytes to identify protective mechanisms that prevent tau toxicity in the developing human brain (Fiock et al., 2023). Our data has identified a potential, previously unknown, role of tau in impairing astrocyte differentiation, thereby triggering neuroprotective phenotypes in immature astrocytes (Fiock et al., 2023). This suggests that, in the developing brain, otherwise toxic tau secreted by neurons causes adjacent astrocytes to remain undifferentiated, provide neurotrophic support, and potentially maintain pluripotency and the ability to transdifferentiate into neurons.