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High-throughput screening for modulators of cellular contractile force.

Publication ,  Journal Article
Park, CY; Zhou, EH; Tambe, D; Chen, B; Lavoie, T; Dowell, M; Simeonov, A; Maloney, DJ; Marinkovic, A; Tschumperlin, DJ; Burger, S; Butler, JP ...
Published in: Integr Biol (Camb)
October 2015

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.

Duke Scholars

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Published In

Integr Biol (Camb)

DOI

EISSN

1757-9708

Publication Date

October 2015

Volume

7

Issue

10

Start / End Page

1318 / 1324

Location

England

Related Subject Headings

  • Myocytes, Smooth Muscle
  • Muscle Contraction
  • Mechanotransduction, Cellular
  • Humans
  • High-Throughput Screening Assays
  • Glaucoma
  • General Science & Technology
  • Fourier Analysis
  • Endothelial Cells
  • Drug Evaluation, Preclinical
 

Citation

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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. Integr Biol (Camb), 7(10), 1318–1324. https://doi.org/10.1039/c5ib00054h
Park, Chan Young, Enhua H. Zhou, Dhananjay Tambe, Bohao Chen, Tera Lavoie, Maria Dowell, Anton Simeonov, et al. “High-throughput screening for modulators of cellular contractile force.Integr Biol (Camb) 7, no. 10 (October 2015): 1318–24. 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. Integr Biol (Camb). 2015 Oct;7(10):1318–24.
Park, Chan Young, et al. “High-throughput screening for modulators of cellular contractile force.Integr Biol (Camb), vol. 7, no. 10, Oct. 2015, pp. 1318–24. Pubmed, doi:10.1039/c5ib00054h.
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. High-throughput screening for modulators of cellular contractile force. Integr Biol (Camb). 2015 Oct;7(10):1318–1324.
Journal cover image

Published In

Integr Biol (Camb)

DOI

EISSN

1757-9708

Publication Date

October 2015

Volume

7

Issue

10

Start / End Page

1318 / 1324

Location

England

Related Subject Headings

  • Myocytes, Smooth Muscle
  • Muscle Contraction
  • Mechanotransduction, Cellular
  • Humans
  • High-Throughput Screening Assays
  • Glaucoma
  • General Science & Technology
  • Fourier Analysis
  • Endothelial Cells
  • Drug Evaluation, Preclinical