Education & Training
- Ph.D. in Molecular Biology from University College Dublin, Ireland, 1996
- BSc. in Pharmacology from University College Dublin, Ireland, 1992
Research Interest Summary
The main interest in the lab is the role of Fibroblast Growth Factor (FGF) signaling in zebrafish organogenesis. Fibroblast growth factors (FGFs) are secreted molecules that activate signaling pathways required for proper embryogenesis. We have established transgenic zebrafish that reports on FGF signaling in live embryos. In these transgenic animals, expression of green fluorescent protein (GFP) is under the control of the Dusp6 promoter, a gene that is regulated by FGFs. These fish act as biosensors for FGF activity and allow the possibility to rapidly screen chemical libraries for novel compounds that modulate the FGF pathway. The goal is to identify chemical probes to investigate the role of FGFs in development. Further, small molecules can potentially be developed into novel therapeutics in the treatment of FGF related disorders. We have identified a compound, BCI, that hyperactives FGF signaling. Our data from computational modeling and biochemistry suggests that this molecule is an allosteric inhibitor of Dusp6. Using BCI as a chemical probe we describe how FGF signaling plays an important role in maintaining cardiac progenitor identity during somitogenesis in the zebrafish. Future avenues of research are to determine the role of FGFs in regeneration and repair, and to develop fully automated high-throughput in vivo chemical screens.
Korotchenko, V*., Saydmohammed, M*., Vollmer, L., Bakan, A., Sheetz, K., Debiec, K., Greene, K., Agliori, C., Gibson, G., Watkins, S., Bahar, I., Day, B., Vogt, A+., Tsang, M.
(2014) In vivo Structure-Activity Relationship Studies support Allosteric Targeting o a Dual Specificity Phosphatase. ChemBioChem 15(10):1436-45
Saydmohammed, M., Vollmer, L., Onuoha, E., Vogt, A., Tsang, M. (2011)
A high-content screening assay in transgenic zebrafish identifies two novel activators of FGF signaling. Birth Defects Research Part C: Embryo Today 93:281-7.
Znosko W., Yu, S., Thomas K., Molina G., Li C., Tsang W., Dawid IB., Moon, AM., Tsang M. (2010)
Overlapping functions of Pea3 ETS transcription factors in FGF signaling during zebrafish development. Development Biology 342:11-25.
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.
Kansara M., Tsang M., Kodjabachian L., Sims N., Trivett M., Ehrich M., Dobrovic A., Snell C., Slavin J., Choong PFM., Simmons PJ., Dawid IB., Thomas DM. (2009)
Epigenetic silencing of Wnt Inhibitory Factor 1 accelerates osteosarcomagenesis in vivo. Journal of Clinical Investigations 119:837-51.
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.
Molina, G., Watkins, SC., Tsang, M. (2007)
Generation of FGF reporter transgenic zebrafish and their utility in chemical screens. BMC Developmental Biology 7:62.
Tsang, M., Meagawa, S., Kiang, A., Habas, R., Weinberg, E., Dawid, I. (2004)
A role for Mkp3 in axial patterning of the zebrafish embryo. Development: 131: 2769-2779.
Tsang, M., Friesel, R., Kudoh, T., Dawid, I.B., (2002)
Identification of Sef: A novel modulator of FGF signaling. Nature Cell Biology 4:165-169.
Kudoh, T*., Tsang, M*., Hukriede, NA., Chen, J., Dedekian, M., Clarke, CJ., Kiang, A., Schultz, S., Epstein, JA., Toyama, R., Dawid, IB. (2001)
A Gene Expression Screen in Zebrafish Embryogenesis. Genome Research 11:1979-1987.