Grad student Bradley Class receives NIH fellowship to advance understanding of rare neurodegenerative disorder

Bradley Class, a 3^rd year PhD student in the lab of Michael Lodato, PhD, has received an NIH predoctoral training fellowship from the National Institute of Neurological Disorders and Stroke (NINDS) to explore single-cell analysis of somatic mutation rates, mechanisms, and impacts in human ataxia telangiectasia cerebellum.

Ataxia telangiectasia is a rare, inherited disorder that primarily affects the cerebellum—the part of the brain that controls muscle movement—resulting in loss of coordination (ataxia) and other neurological symptoms. The disease is caused by mutations in the ATM gene, which encodes a protein that plays a pivotal role in coordinating the repair of DNA double-strand breaks. Mutations in ATM lead to the progressive loss of Purkinje cells (PCs), a rare population of neurons in the cerebellum that are difficulty to study due to their low abundance. Exactly how loss of ATM function affects PC genome stability, and thus PC function, is not well known.

To answer these questions, Class will leverage a protocol he recently developed for isolating PCs from frozen brain samples, and apply single-cell multi-omics to simultaneously analyze both the genome (DNA) and transcriptome (RNA). Using this approach, he will generate a catalog of DNA mutations in PCs to identify mutation “signatures”, and study the relationship between DNA damage and transcriptional changes. The results of the study will provide insight into the changes that occur in PCs in ataxia telangiectasia and the mechanisms that drive PC death—important stepping stones to finding a cure for the disease.

Read the related story from UMass Chan News.