Title
Combination of Reverse and Chemical Genetic Screens Reveals Angiogenesis Inhibitors and Targets
Campus Units
Genetics, Development and Cell Biology
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
4-24-2009
Journal or Book Title
Chemistry & Biology
Volume
16
Issue
4
First Page
432
Last Page
441
DOI
10.1016/j.chembiol.2009.02.010
Abstract
We combined reverse and chemical genetics to identify targets and compounds modulating blood vessel development. Through transcript profiling in mice, we identified 150 potentially druggable microvessel-enriched gene products. Orthologs of 50 of these were knocked down in a reverse genetic screen in zebrafish, demonstrating that 16 were necessary for developmental angiogenesis. In parallel, 1280 pharmacologically active compounds were screened in a human cell-based assay, identifying 28 compounds selectively inhibiting endothelial sprouting. Several links were revealed between the results of the reverse and chemical genetic screens, including the serine/threonine (S/ T) phosphatases ppp1ca, ppp1cc, and ppp4c and an inhibitor of this gene family; Endothall. Our results suggest that the combination of reverse and chemical genetic screens, in vertebrates, is an efficient strategy for the identification of drug targets and compounds that modulate complex biological systems, such as angiogenesis.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Copyright Owner
Elsevier Ltd.
Copyright Date
2009
Language
en
File Format
application/pdf
Recommended Citation
Kalén, Mattias; Wallgard, Elisabet; Asker, Noomi; Nasevicius, Aidas; Athley, Elisabet; Billgren, Erik; Larson, Jon D.; Wadman, Shannon A.; Norseng, Elizabeth; Clark, Karl J.; He, Liqun; Karlsson-Lindahl, Linda; Häger, Ann-Katrin; Weber, Holger; Augustin, Hellmut; Samuelsson, Tore; Kemmet, Chelsy K.; Utesch, Carly M.; Essner, Jeffrey J.; Hackett, Perry B.; and Hellström, Mats, "Combination of Reverse and Chemical Genetic Screens Reveals Angiogenesis Inhibitors and Targets" (2009). Genetics, Development and Cell Biology Publications. 251.
https://lib.dr.iastate.edu/gdcb_las_pubs/251
Comments
This is a manuscript of an article published as Kalén, Mattias, Elisabet Wallgard, Noomi Asker, Aidas Nasevicius, Elisabet Athley, Erik Billgren, Jon D. Larson et al. "Combination of reverse and chemical genetic screens reveals angiogenesis inhibitors and targets." Chemistry & biology 16, no. 4 (2009): 432-441. doi: 10.1016/j.chembiol.2009.02.010. Posted with permission.