Investigator: Sujatha Jagannathan PhD
Category: Research - Basic
When healthy muscle cells grown in the laboratory are forced to make the FSHD causing protein DUX4, they die catastrophically. Studying these dying cells can offer a glimpse into the molecular events set in motion by DUX4 that culminate in cell death. Using engineered muscle cells that express DUX4 synchronously upon addition of a small molecule inducer, we propose to study the downstream consequences DUX4-mediated inhibition of an essential RNA quality control mechanism in the cell. Our hypothesis is that the translation of defective RNAs stabilized by DUX4 could flood the cell with defective and toxic protein products. We will identify such toxic protein products, confirm their presence in FSHD muscle, and assess their contribution to DUX4-induced cell death. As these aberrant RNAs and proteins are unique to DUX4-expressing cells, we will also test their utility as biomarkers for FSHD.