PUBLICATION
Discovery of Biologically Active Oncologic and Immunologic Small Molecule Therapies using Zebrafish: Overview and Example of Modulation of T Cell Activation
- Authors
- Trede, N.S., Heaton, W., Ridges, S., Sofla, H., Cusick, M., Bearss, D., Jones, D., and Fujinami, R.S.
- ID
- ZDB-PUB-130322-10
- Date
- 2013
- Source
- Current Protocols in Pharmacology 14: 4.24 (Chapter)
- Registered Authors
- Trede, Nick
- Keywords
- none
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacology*
- Disease Models, Animal
- Drug Evaluation, Preclinical/methods*
- Humans
- Leukemia, T-Cell/drug therapy
- Leukemia, T-Cell/immunology
- Lymphocyte Activation/drug effects*
- T-Lymphocytes/immunology*
- Zebrafish
- PubMed
- 23456612 Full text @ Curr. Protoc. Pharmacol.
Citation
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. 14:4.24.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping