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. Pathogenic RNA repeats
A variety of neurological disorders, including myotonic dystrophy, amyotrophic lateral sclerosis, and frontotemporal dementia, are caused by the expansion of nucleotide repeats in the human genome. The repeat-containing RNAs transcribed from these loci exhibit unique properties. For example, some RNA repeats undergo phase separation and form distinct foci, which may sequester essential RNA-binding proteins. Some RNA repeats are translated into toxic polypeptides via a noncanonical mechanism. We aim to determine whether and how the structures formed by RNA repeats may contribute to their unusual properties and the associated disease symptoms, with the goal of developing novel diagnostics and therapeutics.
2. Localization of neuronal mRNAs
Spatially precise regulation of gene expression is critical for morphologically complex cells. In neurons, this is achieved in part through the localization of mRNAs to distal compartments in dendrites and axons. Although mRNA localization and local translational control are known to play important roles in neuronal development and plasticity, we do not fully understand the cis-regulatory elements (often being secondary structures) in mRNAs that determine their localization and how these elements function. We aim to systematically identify these structural elements as well as the trans-acting factors that mediate their functions.
3. Noncoding RNA functions in neural development
Since the advent of high-throughput DNA sequencing technologies, the identification of the cellular repertoire of noncoding RNAs has vastly outpaced our understanding of their biological functions. Of the many thousands of small RNAs and long noncoding RNAs in cells, only a small fraction has been functionally characterized. We are interested in developing new tools to interrogate their functions during development of the mammalian nervous system.
Amyotrophic Lateral Sclerosis; Neurons; RNA; Motor Neuron Disease; RNA-Binding Proteins; Computational Biology; Neurodegenerative Diseases; Genomics; RNA Transport; Frontotemporal Dementia; High-Throughput Nucleotide Sequencing