Dan Lu

University of NSW
Cure for Life Neuro-Onclogy Group - Lowy Cancer Research Centre, Pirnce of Wales Clinical School
Rotary Club of North Sydney
Ian McNair Scholarship
Brain Tumours
Funding Partner 2009, 2010 and 2011

Dan received her Bachelor of Biomedical Science with honours from the University of Technology, Sydney in 2007. Her honours project focused on using bioinformatics techniques to search for a novel protein antigen in the Australian paralysis tick, Ixodes holocyclus. In 2008, Dan worked as a research assistant in the Iron Metabolism and Chelation Program at the University of Sydney. Her project was to validate iron chelators as a potential anti-tumour agent, by examining the polyamine pathways in cancer cells. Dan’s science experience also involved a two-month Summer Scholarship Research at the Kolling Medical Research Institute and teaching as a practical class demonstrator. Through her science journey, Dan has acquired broad experiment skills from general molecular biology, tissue culturing to radiation work handling with X-ray machine and radioactive isotopes.

In 2009, Dan was awarded the Australian Rotary Health Ian McNair Scholarship for brain tumour. She is a PhD student in Cure for Life Neuro-Oncology Group, University of New South Wales. Her project is to investigate the genomic alterations in recurrent glioblastoma that characterize tumour relapse and drug resistance. Specifically, she searches for abnormal changes in gene structure that affect downstream transcription and protein expression, which ultimately influence the overall biology of a tumour. By doing this project, Dan further develops her knowledge in epigenetics and she hopes that her results will not only provide molecular details of recurrent glioblastoma but also deliver new targets for cancer treatment.


SUMMARY OF PROJECT:

Unravelling the complexity of glioblastoma relapse and drug resistance

Glioblastoma is the most common and devastating brain tumour in adults. The median survival time is less than 15 months and patients typically have a very poor quality of life. The biggest hurdle of curing this disease is treatment resistance leading to tumour recurrence. The objective of this study is to discover and define key genetic changes underlying in relapsed tumour, which contribute to the malignant and refractory nature of tumour cells. It will enhance current knowledge of cancer biology as well as implicate targeted cancer treatment.

Currently, temozolomide is a standard drug used to treat glioblastoma. It kills cancer cells by attacking the DNA molecules hence inhibiting cell proliferation and reducing tumour growth. MGMT (O6-methylguanine methyltransferase) and MMR (mismatch repair) are DNA repair enzymes that act as guardians and protect cells from external damages. Changes in the expression of these “loyal” enzymes can diminish the effectiveness of cancer treatment.
This project will determine the role of these enzymes in mediating the cytotoxicity of TMZ. Specifically, it will examine the protein expression level as well as modifications of gene structure and changes in nucleotide sequence. Aside from MGMT and MMR, there are other unknown genetic factors acquired during the development of a recurrent tumour.

These include variations in chromosome copy number, single nucleotide polymorphism and microRNA –small piece of RNA that regulates gene transcription. Therefore, a large- scale genomic analysis using matched primary and recurrent patient samples will be undertaken to identify aberrations unique to the relapsed tumour. Eventually these results could help in treatment and/ or prevention of glioblastoma relapse.