Project Grant R01NS144500

Federal Project Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded the University of Arizona $644,814 on July 6, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to support research on tau variants in FUS-mediated amyotrophic lateral sclerosis (ALS). The five-year project, concluding June 30, 2031, will investigate the molecular mechanisms by which specific variants in the microtubule-associated protein tau (MAPT) gene protect unaffected mutation carriers from developing ALS despite carrying the disease-causing FUS R521G mutation. Researchers will generate and analyze induced pluripotent stem cell (iPSC)-derived motor neurons from unaffected carriers, ALS patients, and healthy controls to characterize electrophysiological properties, tau protein expression levels, and the protective role of identified MAPT 3' untranslated region variants in mitigating neuronal hyperexcitability.

The project deliverables include comprehensive molecular and cellular characterization studies utilizing whole genome sequencing, RNA-sequencing analysis, and electrophysiological measurements to elucidate the protective tau variant mechanisms. Research outputs will contribute foundational knowledge toward developing therapeutic interventions for FUS-linked ALS, a currently untreatable neurodegenerative disease. The grant supports basic research aligned with NINDS's mission to reduce the burden of neurological disease through fundamental scientific discovery.