- Identifying the molecular mechanisms of GEMIN5 mutations in a novel cerebellar ataxia syndrome
1R01NS134215-01 07/01/2023 - 06/30/2028 NINDS/NIH Pandey (PI)
GEMIN5 is a key RNA‑binding protein required for healthy brain development and proper RNA processing. Our team discovered that mutations in GEMIN5 cause a previously unrecognized neurodevelopmental disorder marked by motor dysfunction, ataxia, and cerebellar atrophy. This project investigates how loss of GEMIN5 disrupts neuronal health by studying patient‑derived neurons alongside Drosophila and mouse models. We focus on how reduced GEMIN5 levels impair RNA regulation, cellular stability, and mitochondrial function. By defining the underlying mechanisms, this research aims to identify critical disease drivers and pave the way for future therapies for children with rare neurological conditions.
2. Investigating the Contribution of ALS/FTD-Associated Mutations in the NEK1 Kinase to Disease Pathophysiology
1R01NS134166-01 07/01/2023 - 06/30/2028 NINDS/NIH PI: Kiskinis/Pandey
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes loss of motor function and is often associated with frontotemporal dementia. Mutations in the NEK1 gene have recently emerged as a significant genetic contributor to ALS, yet their effects on motor neurons remain unclear. This project investigates how NEK1 mutations disrupt cellular processes using patient‑derived stem cell motor neurons, Drosophila models, and human postmortem tissue. By defining how altered NEK1 function leads to neurodegeneration, this research aims to uncover key disease mechanisms and identify potential therapeutic targets for ALS and related disorders.
