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Douglas D. Boyd

Present Title & Affiliation

Primary Appointment

Professor, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

My laboratory investigates the transcriptional control of the urokinase receptor (u-PAR) gene the product of which contributes to the spread of cancer. We are using transgenic mice and DNaseI hypersensitivity assays to identify novel regions driving tissue-specific u-PAR expression in animals genetically induced for colon cancer. We are also determining which chromatin modifications (focusing on histone phosphorylation) lead to elevated u-PAR expression in invasive cancers.

It is now evident that tumor development/progression reflects the combinatorial action of multiple gene products, each providing some “fitness advantage.” In data-mining for transcripts over expressed in colon cancer, we identified ESTs corresponding to a novel zinc finger protein (ZKSCAN3) as over-represented in this malignancy. Using genetic models (ZKSCAN3 transgenic and null mice) we will determine if expression of the zinc finger protein alone, or with a mutated APC, contributes to intestinal tumor development/progression. Conversely, do mice null for ZKSCAN3 show low colon tumor development in response to azoxymethane or the new Western diet? We will also determine the role of ZKSCAN3 in bladder cancer progression. The predicted ZKSCAN3 protein sequences includes domains (tandem zinc fingers, KRAB domain) typically present in proteins regulatory for gene expression. Using unbiased methods (CAST-ing and expression profiling) we identified putative downstream effectors.
 
In addition to the abovementioned basice science projects, we are also pursuing a joint epidemiology/clinical project with investigators at the USAF School of Aerospace Medicine and the University of Texas Health Science Center in Houston/San Antonio. We have determined that the majority of prostate cancers diagnosed in active duty USAF servicemen are categorized as low-risk. Our project seeks to determine (a) what is the natural history of low-risk disease in servicemen who opt for active surveillance (b) for those who elect for intervention, what type of treatment is selected and the reason(s) for the choice.

Office Address

Phone: 713-563-4918
Email: dboyd@mdanderson.org

Education & Training

Degree-Granting Education

1985 Edinburgh University, Edinburgh, Scotland, PHD, Cell Biology
1982 Leeds University, Leeds, United Kingdom, BSc, Pharmacology

Experience/Service

Other Appointments/Responsibilities

Aviation Safety Committee Member, Aerospace Medical Association, Alexandria, VA, 5/2010-present

Professional Memberships

Aerospace Medical Association
Vice President Resolutions Committee, 2011-present

Selected Publications

Peer-Reviewed Original Research Articles

1. Chauhan S, Goodwin JG, Chauhan S, Manyam G, Wang, J, Kamat, AM, Boyd DD. ZKSCAN3 is a master transcriptional repressor of autophagy. Molecular Cell 11(50):16-28, 2013.
2. Chauhan S, Boyd D. Regulation of u-PAR expression by H2A.Z is modulated by the MEK-/AP-1 pathway. Nucleic Acids Research 40:600-613, 2012.
3. Avila H, Wang H, Chauhan S, Hartig S, Boyd DD. Accelerated urokinase receptor protein turnover triggered by interference with the addition of the glycolipid anchor. Biochemical Journal 434:233-242, 2011.
4. Rogers D, Boyd DD, Fox EE, Cooper S, Goldhagen M, Shen Y, and del Junco DJ. Prostate cancer incidence in USAF Officers: Aviators compared with non-aviators. Aviation Space and Environmental Medicine 82:1067-0170, 2011.
5. Ishiguro T, Lin S-Y, Nakamura T, Yamamoto M, |Boyd. D. Gene trapping identifies chloride channel 4 as a novel inducer of colon cancer cell migration, invasion and metastases. British Journal of Cancer 102(4):774-782, 2/2010.
6. Yang L, Hamilton SR, Sood A, Kuwai T, Ellis L, Sanguino A, Lopez-Berestin G, and Boyd DD. The previously un-described ZKSCAN3 is a novel driver of colorectal cancer progression. Cancer Res 68:4321-4330, 2008. PMID: 18519692.
7. Yang L, Zhang L, Wu Q, Boyd DD. Unbiased screening for transcriptional targets ofZKSCAN3 identifies integrin b4 and vascular endothelial growth factor as downstream targets. Journal of Biological Chemistry 283:35295-35304, 2008. PMCID: PMC2596387.
8. Wang H, Yan C, Asangani I, Allgayer H, Boyd DD. Identification of an histone H3 acetylated/K4-methylated-bound intragenic enhancer regulatory for urokinase receptor expression. Oncogene 26:2058-2070, 2007. PMCID: PMC17001307.
9. Nair RR, Solway J, Boyd DD. Expression cloning identifies transgelin (SM22) as a novel repressor of 92-kDa type IV collagenase (MMP-9) expression. J Biol Chem 281(36):26424-36, 2006. PMID: 16835221.
10. Yan C, Boyd DD. Histone H3 acetylation and H3 K4 methylation define distinct chromatin regions permissive for transgene expression. Mol Cell Biol 26(17):6357-71, 2006. PMID: 16914722.
11. Yang L, Avila H, Wang H, Trevino J, Gallick GE, Kitadai Y, Sasaki T, Boyd DD. Plasticity in Urokinase-Type Plasminogen Activator Receptor (uPAR) Display in Colon Cancer Yields Metastable Subpopulations Oscillating in Cell Surface uPAR Density--Implications in Tumor Progression. Cancer Res 66(16):7957-67, 2006. PMID: 16912170.
12. Yan C, Lu D, Hai T, Boyd DD. Activating transcription factor 3, a stress sensor, activates p53 by blocking its ubiquitination. Embo J 24(13):2425-35, 2005. PMID: 15933712.

Grant & Contract Support

Title: Prostate cancer incidence in the USAF: Implications for screening and treatment in the general US population
Funding Source: NIH
Role: Principal Investigator
Duration: 2010 - 2012
 
Title: Regulation of u-PAR in colon cancer
Funding Source: NIH/NCI
Role: Principal Investigator
Duration: 2009 - 2011

Last updated: 1/31/2014