Poster abstracts
Poster number 113 submitted by Hailey Mulvihill
Novel small molecule screening of CAG expansion clonal inducible cell lines
Hailey Mulvihill (The RNA Institute, University at Albany ), Victoria DeMeo (The RNA Institute, Department of Biological Sciences, University at Albany), Daphne Rincon (The RNA Institute, Department of Biological Sciences, University at Albany), Hannah K. Shorrock (The RNA Institute, Department of Biological Sciences, University at Albany)
Abstract:
Huntington’s disease (HD), spinal and bulbar muscular atrophy (SBMA), and spinocerebellar ataxias (SCAs), specifically SCAs 1, 2, 3, 6, 7, and 12, are a collection of neurodegenerative disorders caused by CAG nucleotide repeats. The CAG RNA repeats code for expanded polyglutamine (polyQ) proteins that misfold and aggregate, disrupting normal cellular functions including protein quality control, synaptic transmission, and transcriptional regulation. Currently, there are no published small molecules that therapeutically target CAG expansion transcripts. This lab has identified a novel small molecule, Hit 2, that reduces the levels of CAG expanded RNA in CAG repeat expansion cell lines. To investigate this therapeutic small molecule, four clonal cell lines were developed with the ability to selectively induce CAG expansion via doxycycline. This study assesses a dosage range of doxycycline for fine tuning of CAG repeat expression across two of the four inducible clonal cell lines and evaluates the effectiveness of Hit 2 on the most expressive cell line, 1-F2.
References:
DeMeo, Victoria, "Developing Cellular Systems to Elucidate RNA Structural Dynamics of CAG Expansion Transcripts in Spinocerebellar Ataxias" (2024). Electronic Theses & Dissertations (2024 - present). 62.
Shorrock, Hannah K. et. al, “CAG repeat-selective compounds reduce abundance of expanded CAG RNAs in patient cell and murine models of SCAs” (2025), in revision.
Keywords: CAG repeat disease, small molecule therapeutics