Douglas Boyd, Ph.D.

1985, Edinburgh University, U.K.

UT M.D. Anderson Cancer Center
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.
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Yan C, Boyd DD (2006) Histone H3 acetylation and H3 K4 methylation define chromatin regions permissive for transgene expression. Mol Cell Biol. 26: 6357-6371.

Yan C, Lu D, Hai T, Boyd DD (2005) ATF3, a stress sensor, activates p53 by blocking its ubuiquitination. EMBO J. 24: 2425-2435.

Nair RR, Solway J, Boyd DD (2006). Expression cloning identifies transgelin (SM22) as a novel repressor of 92 kDa type IV collagenase (MMP-9) expression. J. Biol. Chem 281: 26424-26436.

Wang H, Yang L, Jamaluddin S, Boyd DD (2004). The Kruppel-like KLF4 transcription factor, a novel regulator of urokinase receptor expression, drives synthesis of this binding site in colonic crypt luminal surface epithelial cells. J. Biol. Chem 279: 22674-22683.

Yan C, Wang H, Aggarwal BB, Boyd DD (2004) A novel homologous recombination system to study 92 kDa type IV collagenase transcription demonstrates that the NFkB motif drives the transition from a repressed to an activated state of gene expression FASEB J., 10.1096/fj.03-0960fje.

Wang H, Hicks J, Khanbolooki P, Kim S-J, Yan C, Wang Y, Boyd D (2003) Transgenic mice demonstrate novel promoter regions for tissue-specific expression of the urokinase receptor gene. Am. J. Patholol: 163: 453-464.

Program Affiliation:
Program in Cancer Biology