Role of transforming growth factor beta (TGFß) in pediatric neoplasia
One of the hallmarks of advanced malignancies is the production by tumour cells of TGFß and, paradoxically, the inhibition of TGFß signaling in tumour cells. The group has found through microarray studies that TGFß is markedly up-regulated by the EN protein, and that EN inhibits TGFß signaling. Therefore EN transformation appears to an excellent model of the role TGFß in neoplasia.
Role of the insulin-like growth factor 1 receptor (IGFRI) pathway in pediatric neoplasia
IGFs are expressed in many pediatric malignancies, and it is thought that the IGFRI axis plays a key role in oncogenesis in these tumours. The group recently found that the ETV6-NTRK3 (EN) fusion protein fails to transform IGFRI -/- murine fibroblasts, but that re-introduction of IGFRI restores EN transformation activity. Ongoing studies are assessing mechanisms by which IGFRI complements dominantly acting fusion proteins.
Cyclin D1 regulation in pediatric solid tumours
The abundance of cyclin D1 is rate-limiting in G1 phase progression. The group has found, by microarray and other studies, that several pediatric sarcoma translocation-associated fusion oncoproteins markedly up-regulate cyclin D1 expression. The mechanism of over-expression is currently being assessed by studying transcriptional regulation (such as by the AP-1 and NFKB transcription factors), regulation by the generation of reactive oxygen species (ROS), and regulation of cyclin D1 protein stability by the PI3-kinase-AKT pathway.
Honours & Awards
UBC Pathology Award for Excellence in Research and Discovery - 2001
UBC Pathology Award for Excellence in Research and Discovery - 2014
Research Group Members
Alberto Delaidelli, Graduate Student