Junjie Guo, PhD

1. RNA dysregulation in neurodegenerative diseases

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 repeat sequences in the genome. These mutations can interfere with gene expression and cause neurotoxicty in a variety of mechanisms. We apply molecular and genomic approaches in patient-derived stem cells and neuronal models to investigate these mechanisms and how they impact diseases, with the goal of developing novel therapeutics.

2. Noncanonical mRNA translation in neuronal development and functions

In contrast to the "one mRNA, one protein" dogma, some mRNAs can encode more than one protein isoform. We have recently discovered that mRNAs encoding synaptic organizers such as neuronal pentraxin receptor (NPR) can produce two distinctly localized protein isoforms by having two alternative translation initiation sites. Applying biochemical and transcriptomic approaches in primary neurons and genetically engineered mouse models, we are identifying novel roles of alternative mRNA translation and protein isoforms in synapse formation and functions.

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.