Johns Hopkins School of Medicine

RNA metabolism dysfunction and RNA-targeting therapy in neurodegeneration

The nervous system has extremely complex RNA processing regulation. Dysfunction of RNA metabolism has emerged to play crucial roles in multiple neurological diseases. Mutations and pathologies of several RNA-binding proteins are found to be associated with neurodegeneration in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). An alternative RNA-mediated toxicity arises from microsatellite repeat instability in the human genome. The expanded repeat-containing RNAs could potentially induce neuron toxicity by disrupting protein and RNA homeostasis through various mechanisms. The Sun Lab is interested in deciphering the molecular pathway perturbation caused by disease-linked mutants and develop novel therapeutic strategies. We seek to translate the mechanistic findings at molecular level to biomarker and therapeutic target development to advance treatment options against neurodegenerative diseases.