Albert LaSpada, MD, PhD
Role of senataxin in regulating c9orf72 repeat mediated transcription dysregulation and neurotoxicity in ALS
Mutations in a gene known as senataxin cause a rare form of juvenile-onset ALS. The normal function of senataxin is to regulate how genes are turned into proteins by breaking up pieces of DNA and RNA that get stuck together during the process. Recent work on ALS has shown that the so-called “c9orf72” repeat expansions that cause ALS in human patients promote the formation of such RNA-DNA hybrids. Using a combination of approaches, including studying cell lines from human ALS patients and new mouse models of ALS disease mutations, we will determine if senataxin’s normal role is to regulate the formation of c9orf72 repeat-associated RNA-DNA hybrids and if an interaction between senataxin and the c9orf72 repeat expansion mutation is relevant to the onset and maintenance of ALS.