Oncogenic Transcription Laboratory - LICR Melbourne Centre for Clinical Sciences

MELBOURNE CENTRE FOR CLINICAL SCIENCES

Research > Oncogenic Transcription Lab

Oncogenic Transcription Laboratory

Our laboratory is interested in the mechanisms by which tumor suppressor gene expression is controlled in colon cancer cells. Particularly, we focus on the role played by Histone deacetylases (HDACs), which are a large family of transcriptional co-repressors. Inhibitors of HDACs (HDACi) induce growth arrest, differentiation and apoptosis in colon cancer and other cell lines, and are presently undergoing clinical trial for treatment of colon cancer. The focus of our research is to understand the role specific HDACs play in colon cancer progression using in vitro cell line systems as well as transgenic and knockout mouse models. We also investigate the molecular and biochemical mechanisms by which HDAC inhibitors induce growth arrest, differentiation and apoptosis in colon cancer cells.

A separate focus of our laboratory is the development and application of high throughput genomic technologies such as gene expression profiling, methylation profiling and mutation screening to understand the mechanisms of drug action, and to identify molecular signatures predictive of chemotherapeutic drug response.

Publications

1. Yuan, Z., Shin, J., Wilson, A., Goel, S., Ling, Y.H., Ahmed, N., Dopeso, H., Jhawer, M., Nasser, S., Montagna, C., Fordyce, K., Augenlicht, L.H., Aaltonen, L.A., Arango, D., Weber, T.K., and Mariadason, J.M. An A13 repeat within the 3'-untranslated region of epidermal growth factor receptor (EGFR) is frequently mutated in microsatellite instability colon cancers and is associated with increased EGFR expression. Cancer Res, 69(19): p. 7811-8 2009.

2. Wilson, A.J., Chueh, A.C., Tögel, L., Corner, G., Ahmed, N., Goel, S., Byun, D., Nasser, S., Houston, M., Jhawer, M., Smartt, H., Murray, L., Nicholas, C., Heerdt, B., Arango, D., Augenlicht, L., and Mariadason, J. A coordinated Sp1/Sp3-mediated transcriptional response involving immediate-early gene induction is linked to HDAC inhibitor-induced apoptosis in colon cancer cells. Cancer Research, 2009.

3. Ganepola, G.A., Mazziotta, R.M., Weeresinghe, D., Corner, G.A., Parish, C.J., Chang, D.H., Tebbutt, N.C., Murone, C., Ahmed, N., Augenlicht, L.H., and Mariadason, J.M. Gene expression profiling of primary and metastatic colon cancers identifies a reduced proliferative rate in metastatic tumors. Clin Exp Metastasis, 2009.

4. Wilson, A.J., Byun, D.S., Nasser, S., Murray, L.B., Ayyanar, K., Arango, D., Figueroa, M., Melnick, A., Kao, G.D., Augenlicht, L.H., and Mariadason, J.M. HDAC4 promotes growth of colon cancer cells via repression of p21. Mol Biol Cell, 19(10): p. 4062-75 2008.

5. Mariadason, J.M. HDAC's and HDAC inhibitors in colon cancer. Epigenetics, 3(1): p. 28-37 2008.

6. Jhawer, M., Goel, S., Wilson, A.J., Montagna, C., Ling, Y.H., Byun, D.S., Nasser, S., Arango, D., Shin, J., Klampfer, L., Augenlicht, L.H., Perez-Soler, R., and Mariadason, J.M. PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res, 68(6): p. 1953-61 2008.

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Research Links

	Overview
	Tumour Targeting Laboratory
	Cancer Vaccine Laboratory
	T Cell Laboratory
	Uro-Oncology Laboratory
	Oncogenic Transcription Laboratory
	Joint Austin Ludwig Oncology Unit
	Centre for PET
	Key Technologies

Oncogenic Transcription Lab Staff

Laboratory Head

A/Prof. John Mariadason
Email

Staff Directory

John Mariadason - Laboratory Head
Anderly Chueh - Postdoctoral Fellow
Lars Togel - Postdoctoral Fellow
Sheren Al-Obaidi - Research Assistant
Andrew Weickhardt - M.D. Student

Of Note

Grants

John Mariadason:
NIH R01 Grant 2007-2012
Australia Research Council Future Fellowship 2009-2013

Andrew Weickhardt:
COSA/HSANZ HOTT Fellowship 2009
NH&MRC Scholarship 2009-2011