Zizheng Li, MS
Stratify Sporadic ALS and Pinpoint the Underlying Pathway Dysregulation
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease. Despite extensive research, nearly 90% of patients with sporadic ALS (sALS) and half of those with familial ALS (fALS) lack known genetic causes. sALS is notably heterogeneous, with significant variations among patients, including age of onset, rate of disease progression, severity of associated dementia, and response to therapies. We previously distinguished FUS fALS from healthy controls with machine learning classifiers trained on imaging features, and further identified sALS cases which are phenotypically similar to FUS fALS. I propose to conduct an optical pooled CRISPRi screen to comprehensively characterize the dysregulations which lead to FUS-like phenotypes in sALS. Successful execution of my proposal will enable the discovery of therapeutic targets for FUS-like sALS patients and eventually pave the way for precision treatment for this specific ALS subgroup.
Receiving the PhRMA Foundation Fellowship is a great encouragement and support for me to pursue my novel translational research approach and take a first step toward my career goal of advancing personalized medicine for neurodegenerative diseases.
