Chemical Library Screen

One common research goal of members in the Department of Developmental Biology is to identify small molecules that can be utilized to probe the role of signaling pathways in development. The zebrafish is an important animal model that can be employed in chemical screens. Researchers in Developmental Biology in collaboration with the University of Pittsburgh Drug Discovery Institute have successfully identified new molecules that modulate Fibroblast Growth Factor (FGF) Signaling and chemicals that expand renal progenitor cells in zebrafish. A future direction is to develop automated tools that allow for high content chemical screens using zebrafish. Significant progress includes imaging zebrafish embryos in multi-well plates as well as the development of algorithms to detect fluorescence intensity in zebrafish embryos. Using this technology, researchers have initiated screens to identify compounds that alter FGF activity, angiogenesis, and toxicity in live embryos.  

Relevant Publications:

Tsang, M (2010)
Zebrafish: A tool for Chemical Screens

Birth Defects Research Part C: Embryo Today: Reviews
90(3):185-92.
[Abstract]

Vogt, A., Codore, H., Day, BW., Hukriede, NA., Tsang, M. (2010)

Development of automated imaging and analysis for zebrafish chemical screens

Journal of Visualized Experiments Jun 24;(40). pii: 1900. doi: 10.3791/1900.

[Abstract] [Article]

de Groh ED, Swanhart LM, Cosentino CC, Jackson RL, Dai W, Kitchens CA, Day BW, Smithgall TE, Hukriede NA. (2010)

Inhibition of histone deacetylase expands the renal progenitor cell population.

Journal of the American Society of Nephrology 5:794-802.

[Abstract] [Article]

Vogt A., McPherson PA., Shen X., Balachandran R., Zhu G., Raccor BS., Nelson SG., Tsang M., Day BW. (2009)

High-content analysis of cancer-cell specific apoptosis and inhibition of in vivo angiogenesis by synthetic (–)-pironetin analogs

Chemical Biology and Drug Design 74: 358-368.
[Abstract]

Molina G*., Vogt A*., Bakan A*., Dai W., Queiroz de Oliveira P., Znosko, W., Smithgall TE.,  Bahar I., Lazo JS, Day B., Tsang M.(2009)

Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages.

Nature Chemical Biology 5:680-687.
[Abstract] [Article]

Vogt A., Cholewinski A., Shen X., Nelson S., Lazo J., Tsang M., Hukriede N. (2009)

Automated analysis of angiogenesis in zebrafish embryos by object-based image processing.
Developmental Dynamics 238: 656-663.
[Abstract] [Article]