Dr. Gitler’s group leverages a combination of yeast and human genetics to define biophysical mechanisms of protein misfolding in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson’s disease. In a previous study, Dr. Gitler’s group identified a mutation in ataxin 2 gene that poses a major genetic risk factor and proved to be a therapeutic target. His group also identified dozens of cryptic splicing events in ALS tissue in neurons harboring TDP-43 pathology. This project aims to use genome-wide approaches to reveal additional regulators and therapeutic targets to lower neurodegenerative disease proteins, single-cell transcriptomics to define mechanisms of motor neuron degeneration and explore additional TDP-43 cryptic splicing targets.