Children's Cancer Centre
Research Projects
Project 1 - Genetic analysis of cell death, drug resistance and oncogenic co-operativity in IL-3 dependent lines
We have generated IL-3 dependent cell lines from mice lacking one or more components of the apoptosis pathway. We have also generated similar cell lines from mice lacking components of the IL-3 signaling pathway. Completing the signaling pathway from cytokine receptor to apoptotic effectors is one of the holy grails of apoptosis research. This project attempts to connect this pathway, molecule by molecule, by working downstream from the IL-3 receptor, and upstream from Bcl-2 family members such as Bax, Bak and Puma.
Project 2 - The Regulation And Role Of Puma And P53 In Interleukin-3 (Il-3) Dependent Cell Death
Puma, a pro-apoptotic member of the Bcl-2 family, plays an important role in IL-3 withdrawal induced apoptosis. Puma can be regulated by the tumour suppressor gene, p53. This project is working to understand the role of Puma and p53 in apoptosis provoked by cytokine deprivation.
Project 3 - The role of PI3 Kinase/AKT in IL-3 mediated survival signaling
PI3 Kinase/AKT is thought to be critical in growth factor signaling including survival and proliferation. Using cell lines that lack these kinases or that over-express various constitutively active forms of these proteins, we are studying the role of PI3K/AKT in IL-3 survival signaling.
Highlight Publication
Achievements
- Identified Puma as an important protein in IL-3 withdrawal induced apoptosis
- Shown that deletions of caspase-9 or Apaf-1 does not contribute to clonogenic survival
- 2 successful NHMRC project grants current