RESEARCH APPROACH

The Donnelly lab strives to uncover molecular and cellular dysfunction that underlie fatal neurodegenerative disorders. The goal of our investigation into the pathobiology of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) is to identify novel avenues for therapeutic intervention.

Induced Pluripotent Stem Cell (iPSCs) Cultures

Our lab generates iPSCs from ALS/FTD patient skin cells and differentiates these into live human motor neurons and cortical neurons. This allows us to identify pathways that may contribute to disease onset in live human neurons from patients afflicted with ALS or FTD. Furthermore, these tools provide insight into the etiology of both the genetically inherited (familial) and non-inherited (sporadic) ALS or FTD.

Optogenetic Induction of Neurodegenerative Proteinopathies

Optogenetics is the process of controlling intracellular processes using light-responsive proteins. Our laboratory employs optogenetic-based approaches to initiate intracellular molecular crowding with light. This allows us to treat cells as a test tube to study abnormal protein aggregation, a hallmark of neurodegenerative diseases.

We employ automated longitudinal microscopy to study neural health with high temporal resolution. “The Dax” microscope allows us to examine neuron health and function at single molecule resolution.

Automated Longitudinal Microscopy
ALS and Dementia Modeling using Drosophila

Harnessing the power of Drosophila genetic systems allows us to quickly identify genetic and pharmacological modifiers of neurodegeneration in vivo. We work in collaboration with the Pandey Lab to develop new models of ALS and to perform comprehensive genetic screens to uncover novel pathways that contribute to disease onset.

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