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Mol Biol Cell DOI:10.1091/mbc.E21-10-0481

A Multiparametric Activity Profiling Platform for Neuron Disease Phenotyping and Drug Screening.

Publication TypeJournal Article
Year of Publication2021
AuthorsBoivin, B, Roet, KCD, Huang, X, Karhohs, KW, Rohban, MH, Sandoe, J, Wiskow, O, Maeda, R, Grantham, A, Dornon, MK, Shao, J, Frost, D, Baker, D, Eggan, K, Carpenter, AE, Woolf, CJ
JournalMol Biol Cell
Date Published2021 Dec 15

Patient stem cell-derived models enable imaging of complex disease phenotypes and the development of scalable drug discovery platforms. Current preclinical methods for assessing cellular activity do not, however, capture the full intricacies of disease-induced disturbances, and instead typically focus on a single parameter, which impairs both the understanding of disease and the discovery of effective therapeutics. Here, we describe a cloud-based image processing and analysis platform that captures the intricate activity profile revealed by GCaMP fluorescent recordings of intracellular calcium changes and enables the discovery of molecules that correct 153 parameters that define the amyotrophic lateral sclerosis motor neuron disease phenotype. In a high-throughput screen, we identified compounds that revert the multiparametric disease profile to that found in healthy cells, a novel and robust measure of therapeutic potential quite distinct from unidimensional screening. This platform can guide the development of therapeutics that counteract the multifaceted pathological features of diseased cellular activity.


Alternate JournalMol Biol Cell
PubMed ID34910584
Grant ListR35 GM122547 / GM / NIGMS NIH HHS / United States
R35 NS105076 / NS / NINDS NIH HHS / United States