Research Program

The overarching goal of our research program is to investigate the molecular mechanisms linking tau alterations with cellular dysfunction, and in particular, with RNA translation. These events contribute to the pathogenesis of more than 20 neurodegenerative disorders that share a common pathological hallmark: intracellular aggregation of tau. Tauopathies include Alzheimer’s disease, fronto-temporal dementia with tau inclusions, and chronic traumatic encephalopathy / traumatic brain injury (CTE/TBI), which are central to the focus of my research. With support from NIH and the Alzheimer’s Association, we identified that tau pathogenesis and progression compromises nascent protein synthesis via two distinct pathways: by altering ribosomal function and inducing the PERK pathway of the unfolded protein response. In addition, support from the DoD and the VA contribute to our work in TBI. Finally, we worked with GlaxoSmithKline to validate novel compounds that improve RNA translation in models of tauopathy. Together, their support is bringing us closer to understanding the mechanisms of tau-mediated neurotoxic events stemming from translational dysfunction. Ultimately, this work can aid in the identification of therapeutic targets for more than 30 million people currently suffering from tauopathies world-wide.

Projects

Publications