© Donnelly Lab

RESEARCH INTERESTS

Nuclear pore dysfunction and nuclear transport in neurodegenerative diseases

A hallmark pathological feature of neurodegenerative diseases is the presence of intracellular protein inclusions. These protein inclusions are often found in patients despite any genetic contribution to the disease. In nearly all ALS patients (97%), the TDP-43 protein is mislocalized to the cytoplasm and aggregated in the affected regions of the central nervous system. This is also observed in nearly half of FTD patients (45%) and a majority of Alzheimer’s Disease Patients (60%). The cause of these inclusions remains unclear, and current attempts at modeling this neuropathology are unreliable. We develop and utilize novel optogenetic-based methods to recreate “ALS in a dish” and employ this to study intracellular protein inclusions on neural health and screen for modifiers of these common pathologies. We are also using this approach to other neurodegenerative disease-related proteins such as Tau and alpha-synuclein.

The Etiology of Neurodegenerative Proteinopathies​

A hallmark pathological feature of neurodegenerative diseases is the presence of intracellular protein inclusions. These protein inclusions are often found in patients despite any genetic contribution to the disease. In nearly all ALS patients (97%), the TDP-43 protein is mislocalized to the cytoplasm and aggregated in the affected regions of the central nervous system. This is also observed in nearly half of FTD patients (45%) and a majority of Alzheimer’s Disease Patients (60%). The cause of these inclusions remains unclear and current attempts at modeling this neuropathology are unreliable. We develop and utilize novel optogenetic-based methods to recreate “ALS in a dish” and employ this to study intracellular protein inclusions on neural health and screen for modifiers of these common pathologies. We are also using this approach to other neurodegenerative diseases related proteins such as Tau and alpha-synuclein.