BBS Faculty Member - Joanne Chan

Joanne Chan

Department of Surgery and Vascular Biology Program

Boston Children's Hospital
Karp Family Research Labs, Rm. 12.217
300 Longwood Ave.
Boston, MA 02115
Tel: 617-919-2379
Fax: 617-730-0231
Email: joanne.chan@childrens.harvard.edu
Lab Members: 3 postdoctoral fellows, 1 graduate student, 2 technicians
Visit my lab page here.



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.



Last Update: 8/21/2013



Publications

Bolcome, RE, III, Sullivan, SE, Zeller, R, Barker, AP and Collier, RJ and Chan, J (2008) Anthrax Lethal Toxin Induces Cell Death-Independent Permeability in Zebrafish Vasculature, Proc Natl Acad Sci U S A, 105:2439-2444.

Bayliss PE*, Bellavance KL*, Whitehead, G, Abrams, JM, Aegerter, S, Robbins, HS, Cowan, DB, Keating, MT, O’Reilly T, Wood JM, Roberts TM and Chan J. (2006) Chemical Modulation of Receptor Signaling Inhibits Regenerative Angiogenesis in Adult Zebrafish. (2006) Nature Chemical Biology 2:265-273. (*equal contributions).

Chan J, Bayliss PE, Wood JM and Roberts TM. (2002) Dissection of angiogenic signaling in zebrafish using a chemical genetic approach. Cancer Cell 1: 257-267.

Chan J, Mably JD, Serluca FC, Chen J, Goldstein NB, Thomas MC, Cleary JA, Brennan C, Fishman MC and Roberts TM. (2001) Morphogenesis of prechordal plate and notochord requires intact Eph/ephrin B signaling. Developmental Biology 234: 470-482.



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