Research Grant Award

Research Fellowship Award/Post Doc

Marija Cvetanovic, PhD

Northwestern University
Molecular mechanism of transcription alterations in SCA 1

Spinocerebellar ataxia1 (SCA1) is a devastating dominantly inherited disease that causes progressive loss of coordination and death due to pulmonary failure.

It is caused by polyglutamine stretch expansion in protein ataxin-1, which is toxic to neurons. Molecular mechanism of ataxin-1 toxicity is still unclear. Previous studies have established transcriptional misregulation as the earliest detectable change in SCA1. We envision ataxin-1 induced transcriptional misregulation in SCA1 to be underlying cause of neuronal toxicity. We hypothesize that ataxin-1 regulate transcription via modification of histone acetylation. Indeed, in this regard, we have already found that cerebella from SCA-1 mice have decreased global levels of acetylated histones, suggestive of inhibited transcription. In this grant, we propose to further explore the role of ataxin-1 in modulating histone acetylation, both in vitro and in vivo and correlate these properties with neurotoxicity.

We hope that our result will help identify the molecular mechanism that underlies neurodegeneration in SCA1, eventually leading to design of rational therapies.