Graduate Program Affiliations

• Biochemistry, Molecular, Cellular and Developmental Biology Graduate Group

Preceptor

• Kassandra Ori-McKenney

Research

Mutations in the microtubule-severing enzyme spastin are responsible for approximately 40% of cases of Hereditary Spastic Paraplegia (HSP), a rare neurodegenerative disorder. HSP is marked by progressive axonal degeneration of corticospinal motor neurons, leading to spasticity and loss of voluntary motor function in the lower limbs. Despite spastin’s central role in microtubule dynamics, the impact of disease-associated mutations on its severing activity and interactions with microtubules remains poorly understood. To address this, I will employ in vitro reconstitution and fluorescence microscopy to dissect the biophysical mechanism of spastin function on microtubules and investigate how mutations may disrupt its regulatory interactions with other microtubule-associated proteins, thereby contributing to HSP pathogenesis.