The Sun Lab explores the fascinating frontiers of RNA metabolism dysfunction and RNA-targeting therapeutics in neurodegenerative diseases. The nervous system has extremely complex RNA processing regulation and 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. We are interested in deciphering the RNA processing pathways altered by the ALS-causative mutants to uncover the mechanisms of toxicity and molecular basis of cell type-selective vulnerability. We also apply various high-throughput screening platforms to identify small molecule and genetic inhibitors of neuronal toxic factors. We aim to bridge basic mechanistic studies and translational disease modeling to decipher molecular mechanism of pathogenesis, identify novel biomarkers and promising drug targets for therapy development by combining innovative techniques and interdisciplinary approaches.
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