Combination of Reverse and Chemical Genetic Screens Reveals Angiogenesis Inhibitors and Targets

Thumbnail Image
Date
2009-04-24
Authors
Kalén, Mattias
Wallgard, Elisabet
Asker, Noomi
Nasevicius, Aidas
Athley, Elisabet
Billgren, Erik
Larson, Jon
Wadman, Shannon
Norseng, Elizabeth
Clark, Karl
Major Professor
Advisor
Committee Member
Journal Title
Journal ISSN
Volume Title
Publisher
Authors
Person
Essner, Jeffrey
Professor
Research Projects
Organizational Units
Organizational Unit
Genetics, Development and Cell Biology

The Department of Genetics, Development, and Cell Biology seeks to teach subcellular and cellular processes, genome dynamics, cell structure and function, and molecular mechanisms of development, in so doing offering a Major in Biology and a Major in Genetics.

History
The Department of Genetics, Development, and Cell Biology was founded in 2005.

Related Units

Journal Issue
Is Version Of
Versions
Series
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.

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.

Description
Keywords
Citation
DOI
Copyright
Thu Jan 01 00:00:00 UTC 2009
Collections