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Oncogenic transcription

Laboratory overview

Our lab investigates the role epigenetic regulatory proteins play in the onset of colon cancer, with the goal of identifying new treatment targets for this disease. We also seek to discover molecular biomarkers which can predict response to targeted therapeutics used in the treatment of colon cancer and other gastrointestinal malignancies.

The goal of our laboratory is to improve the outcomes for patients affected with colon and other gastrointestinal cancers. We’ll achieve this by identifying new treatment targets. PROF. JOHN MARIADASON. HEAD, ONCOGENIC TRANSCRIPTION LABORATORY
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Our focus

Epigenetic Therapy

Our laboratory investigates the role epigenetic regulatory proteins play in the progression of colon cancer and other gastrointestinal malignancies, with the goal of targeting these molecules as a potential treatment for these diseases. Specifically, we have demonstrated that histone deacetylases (HDACs) and bromodomain-containing proteins are required for colon cancer cell growth, and have demonstrated that inhibitors of these enzymes induce growth arrest and apoptosis in colon cancer cell lines. Through investigation of their mechanism of action we are seeking to advance these agents as novel treatments for gastrointestinal cancers.

Differentiation Therapy

Our laboratory also investigates the transcriptional mechanisms by which cellular and tissue differentiation is perturbed during colorectal tumorigenesis. We have identified a number of key transcription factors that are deregulated during this process, and we are using this information to investigate mechanisms by which differentiation can be reprogrammed in tumour cells.

Discovery of biomarkers to targeted therapies

Through access to clinical trial samples provided by our long-term collaborator A/Professor Niall Tebbutt, our laboratory has an active translational research program aimed at discovering biomarkers predictive of response to targeted therapeutics in gastrointestinal cancers. Agents we are investigating include anti-angiogenic therapeutics (avastin), EGFR inhibitors (cetuximab), BRAF inhibitors and mTOR inhibitors, in colorectal cancer, gastric cancer and cholangiocarcinoma.

 

Quick facts

What is a gene?

A gene is a small, functional unit of our DNA, containing the information, or 'instructions' to produce other functional units, such as proteins.

What is transcription?

Transcription is the process the cell uses to transfer the information contained within the DNA into a format that can be used to inform the production of proteins.

What is a gene's role in cancer?

Cancer is a genetic disease. When a gene is mutated, the gene may become unable to provide the right information and instructions to the proteins it informs. As such, the cell is unable to perform its proper job. This can lead to cancer.

What is a protein?

Proteins are molecules consisting of amino acids, which the cells in the human body need to function properly. Each cell may have thousands of different proteins, each with it's own instructions for that cell or those that it interacts with. When the proteins work together they ensure the cell does its job.

1.     Shin J, Carr A, Corner GA, Tögel L, Dávalos-Salas M, Tran H, Chueh AC, Al-Obaidi S, Chionh F, Ahmed N, Buchanan DD, Young JP, Malo MS, Hodin RA, Arango D, Sieber OM, Augenlicht LH, Dhillon AS, Weber TK, Mariadason JM. The Intestinal Epithelial Cell Differentiation Marker ALPi is Selectively Induced by HDAC Inhibitors in Colon Cancer Cells in a KLF5-dependent Manner. J Biol Chem. 2014,  289: 25306-16.

2.     Rodrigues P, Macaya I, Bazzocco S, Mazzolini R, Andretta E, Dopeso H, Mateo-Lozano S, Bilić J, Cartón-García F, Nieto R, Suárez-López L, Afonso E, Landolfi S, Hernandez-Losa J, Kobayashi K, Cajal SR, Tabernero J, Tebbutt NC, Mariadason JM, Schwartz S Jr, Arango D. RHOA inactivation enhances Wnt signalling and promotes colorectal cancer. Nat Commun. 2014, 5:5458.

3.     Mouradov D, Sloggett C, Jorissen RN, Love CG, Li S, Burgess AW, Arango D, Strausberg RL, Buchanan D, Wormald S, O'Connor L, Wilding JL, Bicknell D, Tomlinson IP, Bodmer WF, Mariadason JM*, Sieber OM*. Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer.Cancer Res. 2014, 74(12):3238-47 *Corresponding authors.

4.     Anderly C. Chueh, Janson W.T Tse, Lars Tögel, John M. Mariadason. Mechanisms of HDAC inhibitor regulated gene expression in cancer cells (Review). Antioxid Redox Signal, 2015. 23(1): p. 66-84.. 

5.     Weickhardt AJ, Price J, Chong G, Gebski V, Pavlakis N, Johns T, Azad A, Skrinos E, Fluck K,  Dobrovic A, Salemi R, Scott AM, Mariadason JM*, Tebbutt NC*. Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: preclinical evaluation and results of the phase II DUX study in chemotherapy-refractory, advanced colorectal cancer. J Clin Oncol 30(13):1505-12, 2012.  *Co-corresponding authors.

For a complete list of John M. Mariadason's publications, click here.

Meet our team

David Lau

May 30, 2017, 17:05 PM
Position : PhD Student
Theme : Blue

My translational research interests involve clinical trials evaluating targeted biologic agents, particularly early phase trials with targeted antibodies. Along with the development of investigator initiated clinical trial concepts, the application of immunotherapies and cancer vaccines to clinical trials.

In addition to participation in melanoma and hepatoma cancer clinics, my principal responsibilities involve the management of patients involved in early phase clinical trials with oncological malignancy: protocol development, regulatory affairs, trial conduct in line with GCP, and all aspects of trial clinical and administrative management and reporting.

In 2004 I completed my Bachelor of Medicine, Bachelor of Surgery degree at the University of Western Australia in Perth.  In 2010 I completed studying the basic physician training at the Royal Australasian College of Physicians. Since then I have been an advanced Medical Oncology trainee.

Education

2010      Current: Advanced Medical Oncology trainee

2010       Basic Physician Training - Royal Australasian College of Physicians

2004       Bachelor of Medicine, Bachelor of Surgery - University of Western Australia, Perth

 

 Email: david.lau@onjcri.org.au

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