Goals
- Discover novel highly specific small molecule tools
- Provide a Portal to explore Chemotype-phenotype relationships in zebrafish
- Facilitate distribution of discoveries
- Platform for democratization of development of discoveries
- Reduce time take to develop discovery into translatable tool
Our philosophy is based on the premise that the crowd has more aggregate knowledge than the individual. Our unbiased phenotypic screening platform is capable of identifying highly selective and potent molecules, but outstrips the expertise and capabilities of any individual lab. This initiative is driven to disseminate our small molecule technologies to enable niche experts to leverage their knowledge and tools to develop novel therapeutic hypotheses and therapeutic entities for human health.
Background
Chemical genetics involves the discovery, development and use of chemical probes for interrogation of biological processes and for translational discoveries. In a manner analogous to classic forward mutagenesis screens, the Hong lab has conducted an unbiased, high-throughput chemical screen for small molecules that specifically modulate early embryonic development in zebrafish, and has carried out the follow-up task of identifying the pharmacological targets of a number of developmental modulators.
Using this target-agnostic, “high content” phenotypic screening platform, we have discovered novel BMP, Wnt and hedgehog inhibitors, as well as first-in-class modulators of cell signaling components. Moreover, since disturbances in developmental pathways play central role in the pathogenesis of many human illnesses, small molecules that selectively target them have significant translational potential. For instance, we have licensed our BMP inhibitor technology for clinical development toward a number of diseases caused by aberrant BMP signaling. In addition, leveraging the available molecular genetic information on early zebrafish embryogenesis, we have developed unbiased computational methods to map the actions of small molecules and accelerate target identification. However, the growing repository of hit compounds far outstrips our ability for target identification, which frequently require diverse array of expertise and reagents. The Chemical Phenomics Initiative is an interactive web portal through which our chemotype-phenotype database and hit compounds will be made accessible to the scientific community to overcome extant resource barriers that currently limit the impact of chemical genetics and to maximize the translational potential of this effort.
Funding
(1R01GM118557-01)
Collaborators and Partners
