Cerebral Tumour Research Laboratory
Head of laboratory
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Research Assistant Sanaz Maleki preparing the autostainer for high throughput immunohistochemistry. |
On this page:
- Overview of research program
- Major funding sources
- Selected publications
- Major collaborations
- Research project opportunities
Overview of research program
The overall objective of the Cerebral Tumour Research group is to discover biomarkers that have prognostic and predictive significance in brain and pituitary tumours. High grade brain tumours are a universally fatal disease with a median survival of just 15 months. Brain tumours have an extraordinary capacity to migrate long distances and infiltrate the normal brain, making complete surgical removal impossible. The currently available adjuvant therapies for patients: radiation therapy and chemotherapy, have limited effectiveness as a result of this invasiveness but also because of their high resistance to therapies. Consequently, the molecular targets involved in the invasive and chemoresistant processes need to be identified so that new therapeutic strategies can be established to reduce further tumour spread and improve overall survival.
Whilst pituitary tumours are associated with a much more optimistic survival outlook, they can cause significant morbidity and premature mortality can result from mass effect and hormonal dysfunction. The genetic factors that cause pituitary tumorigenesis are largely unknown. In addition, there is a lack of new chemotherapies that can help reduce the invasiveness post-surgery. The approach for both brain and pituitary tumour research is to simultaneously profile genes to identify key biological targets.
Laboratory techniques commonly used include microarray hybridization and analysis, quantitative PCR, gene silencing and over-expression in vitro, mutation sequencing, Western blot analysis and high throughput immunohistochemistry. The majority of research conducted in the cerebral tumour research group is carried out on fresh frozen human brain and pituitary tumours stored in the Australasian Brain Tumour Bank. In vitro and in vivo models are used to validate the discoveries and elucidate the mechanisms.
Major funding sources
- Sydney Neuro-oncology Group (SNOG)
- Andrew Olle Memorial Foundation
- Cancer Council NSW
- Cancer Institute NSW
- Cure For Life Foundation
Selected publications
Payne CA, Maleki S, Messina M, O’Sullivan MG, Stone G, Hall N, Parkinson JF, Wheeler HR, Cook RJ, Biggs MT, Little NS, Teo C, Robinson BG, McDonald KL. (2008) Loss of Prostaglandin D2 Synthase: A key molecular event in the transition of a low grade astrocytoma to an anaplastic astrocytoma. Molecular Cancer Therapies. 7(10):3420-8
Au AYM., McDonald K, Gill A, Diamond T, Sywak M, Conigrave AD, Clifton-Bligh RJ. (2008) PTH Mutation Associated with Primary Hyperparathyroidism and Undetectable intact PTH. New Eng J Med. 359, 1184-86
Soon PSH, McDonald KL, Robinson BG, Sidhu SB (2008). Molecular markers and pathogenesis of adrenocortical cancer. The Oncologist. 13(5) 548-61
Fowler AR, Cook RJ, Biggs M, Little N, Assad N, McDonald KL (2008). Neurosurgical Colonic Adenocarcinoma Metastasis in Northern Sydney/ Central Coast Area Health Service: A Review. J Clinical Neuroscience. 15, 998-1004
Elston MS, Gill AJ, Conaglen JV, Clarkson A, Shaw JM, Law AJ, Cook RJ, Little NS, Clifton-Bligh RJ, Robinson BG, McDonald, KL (2008) Endocrinology 149: 1235-42
Parkinson JF, Wheeler HR, Clarkson A, McKenzie CA, Biggs MT, Little NS, Cook RJ, Messina M, Robinson BG, McDonald KL (2008) Variation of 06-methylguanine-DNA methyltransferase (MGMT) promoter methylation in serial samples in glioblastoma. J Neurooncol. 87:71-8
Parkinson JF, Wheeler HT & McDonald KL (2008) Contribution of DNA repair mechanisms to determining chemotherapy response in high grade glioma J Clin Neuroscience 15: 1-8
Soon PSH, Libe R, Benn DE, Gill A, Shaw JM, Martin E, Bambach C, Campbell P, Sywak MS, Groussin L, Bertagna X, Gicquel C, Bertherat J, McDonald KL, Sidhu SB, Robinson BG. (2008) Loss of Heterozygosity of 17p13, with Possible Involvement of ACADVL and ALOX15B, in the Pathogenesis of Adrenocortical Tumors. Annals of Surgery 247: 157-164
Soon PS, Benn D, Gill A, Robinson BG & McDonald KL Microarray gene expression analysis of human adrenocortical tumours. ANZ J Surg 2007, 77 (Suppl 1) A22
McDonald KL, O’Sullivan MG, Parkinson JF, Shaw JM, Payne CA, Brewer JM, Young L, Reader DJ, Wheeler HT, Cook RJ, Biggs MT, Little NS, Teo C, Stone G, Robinson BG. IQGAP1 and IGFBP2: Valuable biomarkers for determining prognosis in glioma patients. J Neuropath Exp Neurol 2007; 66:405-17
Major collaborations
- Professor Roger Reddel (Children’s Medical Research Institute) and Dr Janice Royds (University of Dunedin, NZ)
Examining the incidence of Alternative Lengthening of Telomeres and Outcome in Glioblastoma patients - Dr Michael Buckland (St Vincents Hospital/ Victor Chang Research Institute)
Oligodendrogliomas with LOH 1p/19q: Identifying genes and methylation hot spots associated with therapeutic sensitivity - Dr David Ziegler (Sydney Children’s Hospital)
Investigating the expression of ARC at the protein level, by performing immunohistochemical analysis on samples from the Australasian Brain Tumour Bank
Research project opportunities
Supervised by Dr Kerrie McDonald
