Unit

UNIT 14.24 Discovery of Biologically Active Oncologic and Immunologic Small Molecule Therapies using Zebrafish: Overview and Example of Modulation of T Cell Activation

  1. Nikolaus S. Trede1,2,
  2. William Heaton1,
  3. Suzanne Ridges1,
  4. Hossein Sofla1,
  5. Matthew Cusick3,
  6. David Bearss1,
  7. David Jones1,
  8. Robert S. Fujinami3

Published Online: 1 MAR 2013

DOI: 10.1002/0471141755.ph1424s60

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Trede, N. S., Heaton, W., Ridges, S., Sofla, H., Cusick, M., Bearss, D., Jones, D. and Fujinami, R. S. 2013. Discovery of Biologically Active Oncologic and Immunologic Small Molecule Therapies using Zebrafish: Overview and Example of Modulation of T Cell Activation. Current Protocols in Pharmacology. 60:14.24:14.24.1–14.24.13.

Author Information

  1. 1

    Department of Oncological Sciences, Huntsman Cancer Institute, Salt Lake City, Utah

  2. 2

    Department of Pediatrics, University of Utah, Salt Lake City, Utah

  3. 3

    Department of Pathology, University of Utah, Salt Lake City, Utah

Publication History

  1. Published Online: 1 MAR 2013

Abstract

Zebrafish models continue to gain popularity as in vivo models for drug discovery. Described in this overview are advantages and challenges of zebrafish drug screening, as well as a novel in vivo screen for immunomodulatory compounds using transgenic, T cell reporting zebrafish larvae designed for discovery of compounds targeting T cell leukemia. This assay system allows rapid screening of large numbers of compounds while avoiding the pitfalls of assays based on cell cultures, which lack biologic context and are afflicted by genomic instability. The rationale for this approach is based on similarities of immature normal T cells and developmentally arrested, malignant lymphoblasts in mammalian species. The screening algorithm has been used to identify a nontoxic compound with activity in both acute leukemia models and models of multiple sclerosis, demonstrating the utility of this screening procedure. Curr. Protoc. Pharmacol. 60:14.24.1-14.24.13. © 2013 by John Wiley & Sons, Inc.

Keywords:

  • zebrafish;
  • leukemia;
  • immunomodulatory agents;
  • multiple sclerosis;
  • melanoma;
  • pancreatic carcinoma;
  • liver cancer;
  • rhabdomyosarcoma;
  • testicular cancer;
  • small molecule drug screening