High-throughput screening for modulators of cellular contractile force

Chan Young Park, Enhua H. Zhou, Dhananjay Tambe, Bohao Chen, Tera Lavoie, Maria Dowell, Anton Simeonov, David J. Maloney, Aleksandar Marinkovic, Daniel J Tschumperlin, Stephanie Burger, Matthew Frykenberg, James P. Butler, W. Daniel Stamer, Mark Johnson, Julian Solway, Jeffrey J. Fredberg, Ramaswamy Krishnan

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

When cellular contractile forces are central to pathophysiology, these forces comprise a logical target of therapy. Nevertheless, existing high-throughput screens are limited to upstream signalling intermediates with poorly defined relationships to such a physiological endpoint. Using cellular force as the target, here we report a new screening technology and demonstrate its applications using human airway smooth muscle cells in the context of asthma and Schlemm's canal endothelial cells in the context of glaucoma. This approach identified several drug candidates for both asthma and glaucoma. We attained rates of 1000 compounds per screening day, thus establishing a force-based cellular platform for high-throughput drug discovery.

Original languageEnglish (US)
Pages (from-to)1318-1324
Number of pages7
JournalIntegrative Biology
Volume7
Issue number10
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

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Glaucoma
Modulators
Screening
Asthma
Throughput
Endothelial cells
Canals
Drug Discovery
Smooth Muscle Myocytes
Muscle
Endothelial Cells
Cells
Technology
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Park, C. Y., Zhou, E. H., Tambe, D., Chen, B., Lavoie, T., Dowell, M., ... Krishnan, R. (2015). High-throughput screening for modulators of cellular contractile force. Integrative Biology, 7(10), 1318-1324. https://doi.org/10.1039/c5ib00054h

High-throughput screening for modulators of cellular contractile force. / Park, Chan Young; Zhou, Enhua H.; Tambe, Dhananjay; Chen, Bohao; Lavoie, Tera; Dowell, Maria; Simeonov, Anton; Maloney, David J.; Marinkovic, Aleksandar; Tschumperlin, Daniel J; Burger, Stephanie; Frykenberg, Matthew; Butler, James P.; Stamer, W. Daniel; Johnson, Mark; Solway, Julian; Fredberg, Jeffrey J.; Krishnan, Ramaswamy.

In: Integrative Biology, Vol. 7, No. 10, 01.10.2015, p. 1318-1324.

Research output: Contribution to journalArticle

Park, CY, Zhou, EH, Tambe, D, Chen, B, Lavoie, T, Dowell, M, Simeonov, A, Maloney, DJ, Marinkovic, A, Tschumperlin, DJ, Burger, S, Frykenberg, M, Butler, JP, Stamer, WD, Johnson, M, Solway, J, Fredberg, JJ & Krishnan, R 2015, 'High-throughput screening for modulators of cellular contractile force', Integrative Biology, vol. 7, no. 10, pp. 1318-1324. https://doi.org/10.1039/c5ib00054h
Park CY, Zhou EH, Tambe D, Chen B, Lavoie T, Dowell M et al. High-throughput screening for modulators of cellular contractile force. Integrative Biology. 2015 Oct 1;7(10):1318-1324. https://doi.org/10.1039/c5ib00054h
Park, Chan Young ; Zhou, Enhua H. ; Tambe, Dhananjay ; Chen, Bohao ; Lavoie, Tera ; Dowell, Maria ; Simeonov, Anton ; Maloney, David J. ; Marinkovic, Aleksandar ; Tschumperlin, Daniel J ; Burger, Stephanie ; Frykenberg, Matthew ; Butler, James P. ; Stamer, W. Daniel ; Johnson, Mark ; Solway, Julian ; Fredberg, Jeffrey J. ; Krishnan, Ramaswamy. / High-throughput screening for modulators of cellular contractile force. In: Integrative Biology. 2015 ; Vol. 7, No. 10. pp. 1318-1324.
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