Our laboratory is interested in the mechanisms by which tumour 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.

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Histone deacetylase inhibitors (HDACi) are an emerging class of chemotherapeutic agents which induce growth arrest and apoptosis in tumor cells. We have identified a unique transcriptional response selectively induced by HDACi in colon cancer cells responsive to this class of agents.

1. HDACs and HDAC inhibitors in colon cancer. JM Mariadason. Epigenetics. 2008 Jan-Feb;3(1):28-37.

2. HDAC4 promotes growth of colon cancer cells via repression of p21. AJ Wilson, D-S Byun, S Nasser, LB Murray, K Ayyanar , D Arango, M Figueroa, A Melnick, G Kao, LH. Augenlicht and JM. Mariadason. Mol. Biol. Cell. 2008. 19: 4062-4075.

3. Class I Histone deacetylases are upregulated in human colonic tumors and are linked to reduced cell differentiation in vivo and in vitro. AJ Wilson, DS Byun, HJ Smartt, K L'Italien, Y Sowa, D Arango, LH Augenlicht and JM Mariadason. J. Biol. Chem. 2006 May 12;281(19):13548-58.

4. PIK3CA/PTEN mutation status predicts response of colon cancer cells to cetuximab. M Jhawer, S. Goel, YH Ling, D-S Byun, A Wilson, S Nasser, J Shin, D Arango, L Augenlicht, R Perez-Soler, JM Mariadason. Cancer Res, 2008, Mar 15;68(6):1953-61