Research & Publications
The Guo lab studies RNA regulation in health and diseases of the nervous system, taking a combination of computational, biochemical, genetic, and genomic approaches.
Extensive Research Description
1. RNA dysregulation in nucleotide repeat expansion-associated neurodegeneration
An increasing number of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have been linked to the instability and expansion of nucleotide repeats in the genome, involving a variety of disease mechanisms. For example, some repeat sequences interfere with transcription and pre-mRNA processing. Some repeat RNAs form aggregates and sequester RNA-binding proteins. Others are translated into toxic polypeptides. We aim to determine the causes of these distinctive properties and how they impact disease, with the goal of developing new therapeutics.
2. Noncanonical translation mechanisms
Deviations from canonical translation can occur during each step of mRNA translation (initiation, elongation, and termination). For example, initiation at non-AUG codons plays important roles in regulating canonical translation in normal cells, but also causes the production of toxic peptide from repeat RNAs in neurological disorders. Many RNA viruses employ ribosomal frameshifting to regulate translation of essential viral proteins. We are investigating both physiological and pathological roles of these noncanonical translation mechanisms.
3. Neuronal mRNA transport and local translation
In polarized cells like neurons, newly transcribed mRNAs are often trafficked to distinct subcellular locations (e.g., dendrites and axon), where they can be locally translated in response to external stimuli. We are developing novel technologies that can help better understand the spatial and temporal regulation of mRNA transport and local translation.
Amyotrophic Lateral Sclerosis; Neurons; RNA; Motor Neuron Disease; RNA-Binding Proteins; Computational Biology; Neurodegenerative Diseases; Genomics; RNA Transport; Frontotemporal Dementia; High-Throughput Nucleotide Sequencing