Dr. Douglas D. Boyd
The University of Texas M.D. Anderson Cancer Center
Department of Cancer Biology
My research focuses on the transcriptional control of genes contributing to cancer spread (metastasis). One of these genes is the urokinase receptor (u-PAR) and we are using transgenic mice and DNaseI hypersensitivity assays to identify novel regions driving tissue-specific expression. We will cross our transgenic mice with mucin2 -/- mice to genetically induce colon cancer allowing an analysis of transcriptional requirements in colon cancer in vivo. We also study the regulation of 92 kDa type IV metalloproteinase (MMP-9) expression since this gene is required for tumor progression especially for cancers metastatic to the bone. We focus on how the chromatin environment regulates its expression using recombinant technology to genomically-integrate MMP-9 promoter-reporter constructs in a site-specific manner.
We are also employing an expression cloning strategy in combination with bioinformatics approaches to identify novel regulators of both u-PAR and MMP-9 synthesis of relevance to their over-expression in cancer. To date, we have identified 2 hitherto unknown modulators of u-PAR and MMP-9 expression (KLF4 and SM22 respectively).
Finally, using bioinformatics panning (Unigene Cluster Analysis) and “wet lab” methods (CAST-ing, expression profiling, gene knockdown), we have identified a novel gene (ZKSCAN3) encoding a master regulator of gene expression that drives progression of a colon cancer subset unaltered in genes typically mutated in this malignancy. We are currently identifying downstream effectors of ZKSCAN3 on the basis of gene knockdown(s) compromising the effects of this master regulator on tumor progression.