Pre-clinical models of cyclin E1 amplified high-grade serous ovarian cancer
Despite aggressive surgery and chemotherapy, a majority of women with high-grade serous ovarian cancer (HGSC) recur. We have shown that amplification of CCNE1 is associated with primary chemotherapy resistance in HGSC (Etemadmoghadam et al, 2009 Clin Can Res; 2010 PLoS ONE; 2012 J Path; 2013 Clin Can Res and 2013 PNAS). CCNE1 amplification also occurs in breast, lung and GI cancers.
We have a world leadership position in the development of targeted therapies for CCNE1. This project aims to further advance novel therapeutic approaches to targeting Cyclin E1 (CCNE1) gene amplification. Cyclin E1 is a key regulator of G1-S transition and forms a complex with CDK2. We have demonstrated that CCNE1 amplified tumour cells are sensitive to inhibition of CCNE1/CDK2 activity using gene knockdown and small molecule inhibitors.
This study will involve the development and characterisation of patient derived xenografts and genetically engineered mouse (GEM) models of CCNE1 amplified HGSC. The student will learn key molecular and cell biology techniques, use of transgenic and GEM models and also be exposed to large-scale functional and genomic studies, including high-throughput drug screens and next generation sequencing. The project has significant potential for clinical translation.
All PhD students at Peter Mac must have a scholarship from The University of Melbourne or through another government, trust or philanthropic organisation. Before applying for a scholarship, you must have agreed on a project with an institute supervisor.
For further information regarding scholarships (both local and international), see http://research.mdhs.unimelb.edu.au/scholarships
Closing dates for applications for scholarships to commence in 2016: Round 1 -31 October 2015; Round 2 - 18 Dec 2015