Joanne Chan


Department of Surgery and Vascular Biology Program
Children's Hospital
Karp Family Research Laboratories, Room 12.217
300 Longwood Ave.
Boston, MA 02115-5737
Tel: (617) 919-2379
Fax: (617) 730-0231
Email: Joanne.chan@childrens.harvard.edu
Web Page: The Chan Lab Page
2 postdoctoral fellows, 2 graduate students,

1 technician

 

My research is focused on defining the molecular mechanisms governing blood vessel formation, as many of these genes are re-activated in human diseases. My lab uses molecular, chemical genetic and genetic approaches to examine angiogenesis and receptor signaling using the zebrafish as a model system.

 

The transparency of the zebrafish embryo, its external development and the ability to survive for the first few days of life without a functional circulatory system, make it possible to study genes with critical functions in angiogenesis. As a vertebrate organism, zebrafish genes encoding receptor signaling pathways are highly conserved with their mammalian counterparts. This has facilitated our use of a small molecule inhibitor against the vascular endothelial growth factor receptor (VEGFR) to regulate angiogenesis in the fish with the potency and precision approaching a genetic knockout. This chemical genetic approach has allowed us to demonstrate that over-expression of AKT, a downstream component of VEGFR signaling, can rescue an upstream loss of receptor function induced by the inhibitor in an intact embryo (Chan et al., 2002). We also developed a novel screening strategy that combines chemical inhibition with ENU-mutagenesis to identify angiogenic mutants. Each of our mutant lines displays distinctive vascular defects in angiogenic sprouting, vessel remodeling, and/or heart function. Identification of the defective genes will provide insights into the molecular mechanisms of blood vessel formation that might provide novel targets for the development of anti-angiogenic therapy. With the completion of the zebrafish genome on the horizon, these mutants will facilitate our understanding of vertebrate gene function in development and disease.

 

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BBS webpage updated 12/02/2009