Overview
Topic status: We're looking for students to study this topic.
The family of fibroblast growth factor (FGF) signalling molecules is complex with multiple FGF ligands and receptors. Our laboratory identified mutations in FGFR2 in endometrial cancer (Pollock et al 2007). Inhibition of FGFR by pan-FGFR small molecule inhibitors leads to inhibition of tumor growth and induction of cell death in vitro and in vivo.
Kinase inhibitors have been associated with remarkable clinical responses, however many patients subsequently relapse and develop resistance to these targeted therapies.
Our laboratory has cultured three sensitive cell lines (one breast, two endometrial) in slowly increasing concentrations of Dovotinib and from this selection process has now generated multiple unique isogenic cell lines that are resistant to Dovotinib.
These parental lines (sensitive to FGFR inhibition) and the isogenic cell lines (resistant to FGFR inhibition) will be characterized for differences in cellular phenotypes (growth, differentiation, chemoresistance) as well as differences in gene expression, copy number variation and phosphotyrosine phosphorylation to identify potential molecular mechanisms responsible for the resistance phenotype.
We will then perform a variety of experiments, including gene knockdown and over-expression techniques as well as pharmalogical inhibition of the relevant pathway to validate these mechanisms.
Methods and techniques that will be developed in the course of this project:
- cell and molecular biology and intracellular signalling e.g. Westerns, siRNA/shRNA knockdown, lentiviral transductions, pharmaceutical inhibitors, flow cytometry
- translational cancer cell biology, in vivo xenografts generation
- phosphoproteomics, gene expression profiling, SNP chips, bioinformatics.
- Study level
- PhD, Masters, Honours
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
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Please contact the supervisors.
Dr Pamela Pollock
Professor Judith Clements
