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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 and liver progenitor cells in zebrafish. To acheive these goals, we have developed 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 identified compounds that can promote regeneration in the heart, liver and kidney.
From Molina et. al. Nat Chem Bio. 2009
Chemical Screening Using a Zebrafish Model for Liver Progenitor Cell-Driven Liver Regeneration.
Ko S, Shin D.
Methods Mol Biol. 2019;1905:83-90.
A High-Content Screen reveals New Small-Molecule enhnacers of Ras/Mapk Signaling as Probes for Zebrafish Heart Development.
Saydmohammed M., Vollmer LL, Onuoha EO., Maskrey TS, Gibson G, Watkins SC, Wipf P, Vogt A, Tsang M.
Molecules (2018) Jul 11, 23(7)
Exploiting Analysis of Heterogeneity to Increase the Information Content Extracted from Fluorescence Micrographs of Transgenic Zebrafish Embryos
Shun T, Gough AH, Sanker S, Hukriede NA, Vogt A.
Assay Drug Dev Technol (2017) Aug/Sep;15(6):257-266.
Delayed Treatment with PTBA analogs reduces postinjury real fibrosis after kidney injury.
Skrypnyk NI, Sanker S, Skvarca LB, Novitskaya T, Woods C, Chiba T, Patel K, Goldberg ND, McDermott L, Vinson PN, Calcutt MW, Huryn DM, Vernetti LA, Vogt A, Hukriede NA, de Caestecker MP.
Am J Physiol Renal Physiol (2016) Apr 15;310(8):F705-F716
Bromodomain and extraterminal (BET) proteins regulate biliary-driven liver regeneration
Ko S, Choi TS, Russel JO, So J, Monga SPS, Shin D.
J Hepatol. 2016 Feb;64(2):316-325.
In vivo structure-activity relationship studies support allosteric targeting of a dual specificity phosphatase
Korotchenko VN, Saydmohammed M., Vollmer, LL, Bakan A, Sheetz K, Debiec KT, Agliori CS, Bahar I., Day BW, Vogt A, Tsang M.
Chembiochem (2014) Jul 7:15(10):1436-45
Development of high-content assays for kidney progenitor cell expansion in transgenic zebrafish.Sanker S, Cirio MC, Vollmer LL, Goldberg ND, McDermott LA, Hukriede NA, Vogt A.
J Biomol Screen (2013) Dec;18(10):1193-202.
A high-content screening assay in transgenic zebrafish identifies two novel activators of fgf signaling.
Saydmohammed M., Vollmer LL, Onuoha EO, Vogt A*, Tsang M*.
Birth Defects Res C Embryo Today (2011) Sep;93(3)281-7
Zebrafish: A tool for Chemical Screens
Birth Defects Res C Embryo Today (2010) 90(3):185-92.
Development of automated imaging and analysis for zebrafish chemical screens
Vogt, A., Codore, H., Day, BW., Hukriede, NA., Tsang, M.
J Vis Exp. (2010) Jun 24;(40). pii: 1900. doi: 10.3791/1900.
Inhibition of histone deacetylase expands the renal progenitor cell population.
de Groh ED, Swanhart LM, Cosentino CC, Jackson RL, Dai W, Kitchens CA, Day BW, Smithgall TE, Hukriede NA.
J Am Soc Nephrol (2010) 5:794-802.
High-content analysis of cancer-cell specific apoptosis and inhibition of in vivo angiogenesis by synthetic (–)-pironetin analogs
Vogt A., McPherson PA., Shen X., Balachandran R., Zhu G., Raccor BS., Nelson SG., Tsang M., Day BW.
Chem Biol Drug Des. (2009) 74: 358-368.
Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages.
Molina G*, Vogt A*, Bakan A*, Dai W, Queiroz de Oliveira P, Znosko, W, Smithgall TE, Bahar I, Lazo JS, Day B, Tsang M.
Nat Chem Biol. (2009) 5:680-687.
Automated analysis of angiogenesis in zebrafish embryos by object-based image processing.
Vogt A., Cholewinski A., Shen X, Nelson S, Lazo J, Tsang M*, Hukriede N*.
Dev Dyn (2009) 238: 656-663.