Publications
Discovery of MK-8719, A Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies
Inhibition of O-GlcNAcase (OGA) has emerged as a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer’s disease and progressive supranuclear palsy. Beginning with carbohydrate-based lead molecules, we pursued an optimization [...]
Cytosolic Glucosylceramide Regulates Endolysosomal Function in Niemann-Pick type C Disease
Niemann-Pick type C disease (NPCD) is a neurodegenerative disease associated with increases in cellular cholesterol and glycolipids and most commonly caused by defective NPC1, a late endosomal protein. Using ratiometric probes we find that NPCD [...]
N-Butyldeoxynojirimycin Delays Motor Deficits, Cerebellar Microgliosis, and Purkinje Cell Loss in a Mouse Model of Mucolipidosis type IV
Mucolipidosis type IV (MLIV) is a lysosomal storage disease exhibiting progressive intellectual disability, motor impairment, and premature death. There is currently no cure or corrective treatment. The disease results from mutations in the gene encoding [...]
Mutant Huntingtin Disrupts the Nuclear Pore Complex
Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus [...]