(University of Toronto, Toronto, ON)
Associate Professor, Biochemistry & Molecular Biology
AHFMR Senior Scholar;
Canada Research Chair (Tier II - Genetics/Angiogenesis);
Phone: (403)220-8277 Fax: (403)270-2211
E-mail:
Research Interests:
We are taking a genetic approach to identify new genes involved in angiogenesis, the process by which new blood vessels develop. The cardiovascular system is critical for the survival of vertebrates, and is one of the earliest organ systems to develop in an embryo. Our experimental approach is to identify mutant animals with defects in cardiovascular development during embryogenesis, and then to clone the gene underlying each defect. We then examine the role of these genes in embryonic development and disease. Angiogenesis is altered in many diseases; for instance, it is increased during tumor growth and in diabetic retinopathy. In other cases, impaired angiogenesis can also lead to disease, for instance, in ischemia. The understanding of genes controlling blood vessel growth may therefore lead to new treatments for disease.
Zebrafish as a model system
Zebrafish are a common tropical fish that develop as transparent, externally fertilized embryos. We can observe their development during all stages of embryogenesis under a microscope, in contrast to mammals which develop in utero and are inaccessible. We use zebrafish as a model system because they are small, transparent, and their cardiovascular system develops very similarly to that of mammals. This allows us to do very detailed screens for subtle genetic defects. Each pair of zebrafish lays a large number of eggs each week. This greatly facilitates genetic analysis. Furthermore, as the zebrafish genome is sequenced, it is clear that essentially all of the known genes involved in the establishment of the early vascular system are conserved between fish and mammals.
Recent Publications
Zuccolo, J., Bau, J., Childs, S.J., Goss G.G., Sensen, C.W., Deans, J.P. Phylogenetic analysis of the MS4A and TMEM176 gene families. PLoS One. 2010,5:e9369.
Lamont, R.E., Vu, W., Carter, A.D., Serluca, F.C., MacRae, C.A., Childs, S.J. Hedgehog signaling via angiopoietin1 is required for developmental vascular stability. Mech Dev. 2010, 127:159-68.
Christie, T.L., Carter, A., Rollins, E.L., Childs, S.J. Syk and Zap-70 function redundantly to promote angioblast migration. Dev Biol. 2010, 340:22-9.
Zeng, L., Carter, A.D., Childs, S.J. miR-145 directs intestinal maturation in zebrafish. Proc Natl Acad Sci U S A. 2009, 106:17793-8.
Lamont, R.E., Lamont, E.J., Childs, S.J. Antagonistic interactions among Plexins regulate the timing of intersegmental vessel formation. Dev Biol. 2009, 331:199-209.
Callander, D.C., Lamont, R.E., Childs, S.J., McFarlane, S. Expression of multiple class three semaphorins in the retina and along the path of zebrafish retinal axons.Dev Dyn. 2007, 236:2918-24.
Liu, J., Fraser, S.D., Faloon, P.W., Rollins, E.L., Vom Berg, J., Starovic-Subota, O., Laliberte, A.L., Chen, J.N., Serluca, F.C., Childs S.J. A betaPix Pak2a signaling pathway regulates cerebral vascular stability in zebrafish. Proc Natl Acad Sci U S A. 2007, 104:13990-5.
Georgijevic, S., Subramanian, Y., Rollins, E.L., Starovic-Subota, O., Tang, A.C., Childs, S.J. Spatiotemporal expression of smooth muscle markers in developing zebrafish gut. Dev Dyn. 2007, 236:1623-32.
Lamont, R.E., Childs, S. MAPping out arteries and veins. Sci STKE. 2006, 2006:pe39. Review.
Operating Funds
Canadian Institutes for Health Research
Heart and Stroke Foundation of Alberta, Nunavut and NWT
Natural Science and Engineering Research Council
Canada Foundation for Innovation
