Laura P. W. Ranum Research Group

University of Florida

How do repeat expansion RNAs produce toxic proteins and drive neuron degeneration in ALS, FTD and other disorders? The Ranum Lab discovered that repeat expansion RNAs lacking AUG start codons undergo Repeat Associated Non-AUG (RAN) translation, producing homopolymeric proteins detected in patient brain tissue to study pathogenic protein accumulation. The group develops and characterizes transgenic and BAC mouse models of C9orf72, SCA8 and DM to link repeat-driven RNAs and RAN proteins to neuronal phenotypes using molecular and in vivo optical-imaging strategies. Researchers use high-throughput sequencing and repeat-enrichment strategies to identify novel repeat expansion mutations in genetically undiagnosed ataxia, ALS and dementia families. The lab tests therapeutic strategies that target RAN proteins, including passive immunotherapy and metformin-mediated PKR inhibition, in cell and mouse models to evaluate effects on RAN translation and disease-related outcomes.