In this seminar, Fiona Elwood, Interim Head of Neuroscience Neuroscience at Novartis Institutes for BioMedical Research, will discuss aggregates of hyperphosphorylated tau protein, a pathological hallmark of more than 20 distinct neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, and frontotemporal dementia. While the exact mechanism of tau aggregation is unknown, the accumulation of aggregates correlates with disease progression. Tau is a well-known but challenging drug target and advanced therapeutic strategies have the potential to treat millions of patients globally. To identify novel regulators of tau, two genome-wide CRISPR screens were performed. The first screen, performed in SH-SY5Y cells, identified positive and negative regulators of tau protein levels. The second screen, in HEK-293 cells, used pulse-chase analysis to sort cells that developed tau aggregates and identified distinct regulators of tau aggregation. Hit validation was performed using Ngn2-induced human cortical excitatory neurons and human-brain-derived tau seeding models.
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Fiona Elwood — Fiona Elwood, Ph.D., is the Interim Head of Neuroscience at Novartis Institutes for BioMedical Research. She received a medical degree from King's College London and is board-certified in Neuroscience and Pharmacology.