Endothelial Cell Growth & Signalling
The receptor tyrosine kinase (RTK) family of cell surface proteins is known to play key roles in cell-cell communication in multi-cellular metazoan organisms. Genetic and biochemical studies on this large family of proteins have shown that different RTKs are responsible for transducing important developmental, proliferative, cell survival and migratory signals from the outside to the inside of the cell. The development and proper functioning of cell systems as diverse as the compound eye in the fly, the vulva in the nematode and hematopoiesis and endothelial growth in the mouse all depend on intact signalling pathways that are controlled by different members of the RTK family.
Our lab is investigating the signal transduction pathways
of different RTKs during vascular development in the mouse and
during tumour formation. Vascular endothelial cells constitute an
unusually quiescent epithelial cell population. The turnover rate
of both large and small vessel endothelium is very low. The
mechanisms that underlie this growth control are not well understood,
and the factors which initiate and control subsequent
proliferation are unknown. It is clear, however, that vascular
growth occurs under nonpathological conditions (e.g. wound
healing, corpus luteum formation, and development) and that this
growth is somehow terminated at the correct time. In contrast,
uncontrolled vessel growth (including tumour vascularization,
diabetic retinopathy, and arthritis) are associated with many
different diseased states. The determinants which control these
processes remain unknown; however the study of peptide growth
factors, their receptors and their downstream substrates will
provide both a biochemical and genetic entry point into the elucidation
of the underlying controls of these processes.
Our group uses gene-targeting in embryonic stem cells, transgenic mice, proteomics and receptor biochemistry to attempt to address the importance of these different RTKs and their related signal transduction pathways during vascular growth in development and in disease.
Our research has the potential to impact numerous diseases where aberrant vessel growth or vessel stability lead to progression of disease or increased complications, such as diabetes, heart disease and cancer. Furthermore, our group is also using this knowledge to in fact also augment vessel growth for applications in regenerative medicine.
For further information, please visit our laboratory homepage at http://sunnybrook.ca/research/?page=angiogenicsignallinghome
Graduate Students:
- Vicky Nguyen
Selected References:
Link to Pubmed Publications
