2023 Safadi Pilot Grant Recipients

Paschalis Kratsios, MD
Supervising Faculty

Nidhi Sharma, PhD
Postdoctoral Associate

Department of Neurobiology
In Collaboration with The Departments of Neurology and Chemistry

Dipeptide Repeat (DPR) Aggregation and Lysosomal Impairment in C9ORF72 ALS/FTD

Amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) are devastating, neurodegenerative diseases with no effective treatments. A hexanucleotide repeat expansion GGGGCC in the first intron of humanC9ORF72 is the most common genetic cause of ALS/FTD. The GGGGCC repeats are translated into dipeptide repeat proteins  (DPRs )that are neurotoxic. We have demonstrated that the translation initiation factor eIF2D plays a significant role in  DPRs synthesis in the C. elegans model of C9ORF72ALS/FTDALS. However, eIF2D does act partially; other regulatory factors likely act together with eIF2D as collaborators. The focus of my study is to investigate novel eIF2D collaborators in the DPRs synthesis using a biased and unbiased approach. In addition, I also aim to investigate altered lysosome function upon DPRs aggregation in C. elegans model of C9ORF72ALS/FTDALS using cutting-edge functional and quantitative imaging techniques.