HDAC3 is a transcriptional co-repressor that is overexpressed in several cancers. The goal of this Ph.D project is to dissect the transcriptional mechanism by which HDAC3 gene expression is regulated in colon cancer cells and in the normal colonic epithelium. Specifically, the role of b-cateinin-TCF signaling and the MYC-MAD-MAX transcriptional network on HDAC3 regulation will be examined in detail. This project will provide sound insight into colon cancer biology, and mechanisms of transcriptional regulation.

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

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.

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.

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