Research Grant Award

Puneet Opal, MD, PhD

Northwestern University, Chicago, IL
Dissecting transcriptional misregulation in SCA1 using Laser capture microscopy and transcriptional profiling

Spinocerebellar ataxia type 1 (SCA1) is an inherited disease that causes progressive instability of gait or ataxia. Unfortunately, there is no treatment for this relentless disease and those afflicted succumb to complications of cerebellar and brainstem dysfunction. This disease is caused by an expansion of glutamines (glutamine is an amino acid) in the disease causing protein, ataxin-1. A major shortcoming in our understanding of SCA1 has been the lack of characterization of pathologic changes in Purkinje cells—the cell type most afflicted in this disease. To address this issue we will use laser capture microscopy (LCM), a method designed to purify specific cell populations from tissue samples from pre-symptomatic SCA1 knockin mice. LCM will then be combined with gene-expression profiling to characterize the earliest transcriptional alterations in SCA1. Apart from providing significant insight into SCA1 pathogenesis, we foresee that these experiments will lead to targeted therapies that might reverse the transcriptional alterations seen in this disease.