Topic Overview:
To better understand factors underlying the onset and progression of disease, researchers can approach the issue by studying embryonic development.  Certain processes and pathways that are critical for development are also key in normal adult physiology.  By investigating cellular and molecular developmental processes, one can harness the information to study disease onset and progression as well as to postulate therapeutic targets.     

Fibroblast growth factors (FGFs) constitute a large family of secreted proteins required for proper development and physiological processes. Abnormal embryogenesis and lethality have been show to result from FGF mutations; more specifically, cardiovascular development is critically dependent on FGFs.  To understand the precise role FGFs play in embryogenesis, their spatial and temporal activity must be discerned. 

Vertebrate development research has become increasingly dependent on use of Danio rerio, also known as the zebrafish.  This model organism is well suited to in vivo developmental studies because it has large broods, breeds all year, is easily maintained, develops rapidly, and has transparent embryos that develop outside of the mother.  Researchers can track gene expression during development by tagging a gene of interest with green fluorescent protein (GFP) and observing the whole organism over the developmental period.   

Dr. Tsang’s laboratory is interested in screening for small molecules that modulate the action of FGFs on the Ras-MAPK (mitogen-activated protein kinase) pathway.  Because this pathway is used for multiple aspects of embryogenesis and is critical for cardiac development, creating knockouts at the embryonic stage are often fatal.  However, if Dr. Tsang identifies molecules that disrupt or enhance this pathway, he will be able to control it at later stages of development and understand FGF physiology in the adult.  To find these compounds, his lab has generated a biosensor for FGF activity in live embryos.  Given its small size and optical transparency, researchers can simply observe FGF signaling-based GFP expression in the zebrafish; a compound that successfully blocks FGF signaling will also block GFP expression.   

Dr. Tsang’s development of an in vivo model to easily screen compounds that affect the FGF signaling pathway yields a wealth of information to researchers in drug discovery, developmental biology, and cardiovascular investigation.  It provides a tremendous resource for investigators as well as a good foundation for interdisciplinary collaboration.