Brian Zou
Program: Unspecified
Current advisor:
Undergraduate university: Macalester College
Research summary
Huntington’s disease (HD) is an inherited progressive neurodegenerative disorder, often characterized by progressive motor, cognitive and behavioral impairment. HD leads to premature death and is genetically due to a trinucleotide CAG repeat expansion in the HTT gene. The literature on pathogenesis of HD often focuses on the mutant HTT (mHTT) protein with a prolonged polyglutamine tract that results from CAG repeat expansion. However, post-mortem findings of mHTT aggregates fail to fully represent the cascade of cellular- and molecular- level dysregulation and the complexities of disease progression prior to death. In our work, we are proposing an investigation that directly looks at source: the misfolding of RNA, in an organoid model of Huntington’s Disease. The CAG repeat expansion in the HTT gene has been shown to result in RNA foci; however, disease contribution from RNA foci and details about its’ mechanism, cell-type and organelle-specific localization, and significance are widely underexplored. For my proposed research in the Cremins Lab, we will further explore the role of RNA foci in the pathogenesis of HD and tease apart specific RNA transcripts that result in this misfolded structure, other biomolecules that such RNA structures can interact with, and associated physiological impacts.
Graduate publications