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Protein Quality Control Pathways in ALS

Establishing a high-throughput drug discovery resource to advance understanding of ALS

Full Project Name:Dissecting Protein Quality Control Pathways in ALSPrincipal Investigator:Allison Ebert, PhD, Cell Biology, Neurobiology and AnatomyCo-Investigator:Brian A. Link, PhD, Cell Biology, Neurobiology and Anatomy; Allison Ebert, PhD, Cell Biology, Neurobiology and AnatomyAward Amount:$200,000
Award Date
January2018
Project Duration:24 months

Project Description Narrative:


As our population ages, neurodegenerative diseases afflict an increasing percentage of Americans. Among neurodegenerative diseases, ALS is the most common form of motor neuron disease and is unique in that it affects both the upper and lower motor neurons.

Despite advances in discovering genes that cause hereditary ALS, the mechanism of how these mutations cause ALS is unknown. Currently, few effective medications exist to combat these debilitating disorders and no cures exist.Identifying therapeutic targets and understanding the molecular mechanisms by which these targets act represent key steps toward developing selective and effective therapeutics.

Through this award, researchers aim to establish a high-throughput drug discovery resource at MCW and utilize this resource to identify compounds that accelerate the clearance of aggregation prone proteins that cause ALS.

Outcomes & Lessons Learned:


  • Established a high throughput drug discovery resource at MCW
  • Developed a protocol that reliably detects aggregated proteins in human iPSC-derived neurons
  • Established a journal club with other investigators at MCW who have an interest in neurodegeneration to discuss data and technology
  • Secured external funding to continue the research
  • Began preparing a manuscript for submission to a stem cell-specific journal
  • Presented the work at three local, regional, and international meetings

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