A large number of neurodegenerative diseases are caused by genetic mutations in RNA metabolism genes that are widely expressed throughout the body and are essential to the survival of all cells. These include motor neuron diseases and movement disorders such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Huntington’s disease and various ataxias. The process of cellular degeneration, and why some neurons are particularly susceptible to these genetic changes is poorly understood.

The Arbab lab studies how genetic mutations result in neurological disease and develops gene-based therapeutics to treat them. We use CRISPR genome editing tools, including Cas-nucleases, base editing, and prime editing, to model genetic mutations in cells and probe pathogenic mechanisms that cause neurodegeneration in cell and animal models. We leverage the sensitivity of next-generation sequencing as a read out in high-throughput cellular assays to investigate RNA and protein interactions that go awry in these neurodegenerative diseases. This insight can help us uncover how genetic mutations that are located in broadly expressed genes can result in cell-type specific disease pathology, and help us to discover new areas for drug intervention.

Our ultimate goal is to develop  in vivo precision genome editing treatments for patients of these disorders. develop in vivo delivery strategies using viral and non-viral particles to rescue neurodegeneration in humanized mouse models, and evaluate the safety and efficacy of these approaches for clinical translation.