Research interests: Establishment of normal DNA methylation patterns and how these go awry in cancer, histone modifications and chromatin structure; epigenetic modifications in stem cells and tumor stem cells; development of novel DNA methyltransferase inhibitors

Dr. Keith Robertson once thought about studying architecture, but his work today as a cancer researcher focuses on structures of a different sort, namely the structure or packaging of DNA in a cell's nucleus and the regulation of this structure by DNA methylation.

All cells in an organism have the same DNA. What makes a cell a skin cell or a muscle cell depends upon which genes are expressed, that is, chemically turned on or turned off. DNA methyltransferases (DNMT) are a family of enzymes that regulate gene expression. An abnormality in methylation may promote cancer and other diseases.

"If you take purified DNA methyltransferase and put it on naked DNA, it works — it methylates. But that doesn't quite mimic what happens in the cell," says Dr. Robertson. "Some DNA is methylated in the cell, some is not."

While enzymes are specific in their molecular interactions with substrates, his research and that of other investigators suggest that DNA methyltransferases need to interact with other proteins which guide them to specific regions of DNA to methylate properly. "So we do some of our work in yeast but most of it in mammalian (human) cells to try and identify other proteins that interact with the DNA methylating enzymes," he says.

Work in the laboratory is on the level of basic science, but it is an essential step in understanding the processes in living cells. His goal is to elucidate how enzymes methylate or bind and to identify other factors that may influence their activity. Eventually he hopes to develop and characterize DNA methyltransferase inhibitors to intervene in disease.

Dr. Robertson earned a BS in Biochemistry at Cornell University, Ithaca, N.Y., in 1992, then in 1996 was awarded a PhD in Pharmacology from The Johns Hopkins University School of Medicine, in Baltimore, Md. He has performed post-doctoral work at Hopkins, the Norris Comprehensive Cancer Center, University of Southern California in Los Angeles and the National Institutes of Health in Bethesda, Md. He was an NCI Cancer Scholar before joining the faculty of the University of Florida in Gainsville in 2004 as an assistant professor in the Department of Biochemistry and Molecular Biology.

Dr. Robertson was recently named a Georgia Cancer Coalition Distinguished Cancer Scholar.

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Grants (selected)

• National Cancer Institute: “DNA Methyltransferase Inhibition by Intercalating Agents” 2006–2011, K.D. Robertson, PI
• National Cancer Institute: “De Novo Methyltransferase Function in Chromatin and Cancer” 2009–2013, K.D. Robertson, PI

Grants are updated quarterly.

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Publications (selected)

editorial board:

• Epigenetics

editorial reviewer:

• Cancer Research
• Carcinogenesis
• Clinical Cancer Research
• Epigenetics
• Federation of European Biochemical Societies (FEBS) Letters
• Human Molecular Genetics
• Laboratory Investigation
• Molecular and Cellular Biology
• Molecular Carcinogenesis
• Nature Genetics
• Nucleic Acids Research
• Oncogene
• Proceedings of the National Academy of Sciences
• The Journal of Biological Chemistry
• The Journal of Cell Biology
• The Lancet
• Trends in Biochemical Science (TIBS)

 

Zeng W, de Greef JC, Chen YY, Chien R, Kong X, Gregson HC, Winokur ST, Pyle A, Robertson KD, Schmiesing JA, Kimonis VE, Balog J, Frants RR, Ball AR Jr, Lock LF, Donovan PJ, van der Maarel SM, Yokomori K. Specific loss of histone H3 lysine 9 trimethylation and HP1gamma/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD).

PLoS Genet. 2009 Jul;5(7):e1000559.

Takeda M, Briggs LE, Wakimoto H, Marks MH, Warren SA, Lu JT, Weinberg EO, Robertson KD, Chien KR, Kasahara H. Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation. Lab Invest. 2009 Sep;89(9):983-93.

Gopalakrishnan S, Sullivan BA, Trazzi S, Della Valle G, Robertson KD. DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions. Hum Mol Genet. 2009 Sep 1;18(17):3178-93.

Demircan B, Dyer LM, Gerace M, Lobenhofer EK, Robertson KD, Brown KD. Comparative epigenomics of human and mouse mammary tumors. Genes Chromosomes Cancer. 2009 Jan;48(1):83-97.

Gopalakrishnan S, Van Emburgh BO, Robertson KD. DNA methylation in development and human disease. Mutat Res. 2008 Dec 1;647(1-2):30-8. Review.

Qiu J, Ai L, Ramachandran C, Yao B, Gopalakrishnan S, Fields CR, Delmas AL, Dyer LM, Melnick SJ, Yachnis AT, Schwartz PH, Fine HA, Brown KD, Robertson KD. Invasion suppressor cystatin E/M (CST6): high-level cell type-specific expression in normal brain and epigenetic silencing in gliomas. Lab Invest. 2008 Sep;88(9):910-25.

Jin B, Tao Q, Peng J, Soo HM, Wu W, Ying J, Fields CR, Delmas AL, Liu X, Qiu J, Robertson KD. DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function. Hum Mol Genet. 2008 Mar 1;17(5):690-709.

Palii SS, Van Emburgh BO, Sankpal UT, Brown KD, Robertson KD. DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol. 2008 Jan;28(2):752-71.

Palii SS, Robertson KD. Epigenetic control of tumor suppression. Crit Rev Eukaryot Gene Expr. 2007;17(4):295-316. Review.

Jung Y, Park J, Kim TY, Park JH, Jong HS, Im SA, Robertson KD, Bang YJ, Kim TY. Potential advantages of DNA methyltransferase 1 (DNMT1)-targeted inhibition for cancer therapy. J Mol Med. 2007 Oct;85(10):1137-48.

Chan SL, Cui Y, van Hasselt A, Li H, Srivastava G, Jin H, Ng KM, Wang Y, Lee KY, Tsao GS, Zhong S, Robertson KD, Rha SY, Chan AT, Tao Q. The tumor suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal carcinomas. Lab Invest. 2007 Jul;87(7):644-50.

Brown KD, Robertson KD. DNMT1 knockout delivers a strong blow to genome stability and cell viability. Nat Genet. 2007 Mar;39(3):289-90.

Zhong S, Fields CR, Su N, Pan YX, Robertson KD. Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer. Oncogene. 2007 Apr 19;26(18):2621-34.

Publications are updated quarterly. For a complete listing, see Dr. Robertson's work on PubMed.

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Affiliations

• Associate Professor, Biochemistry and Molecular Biology, Medical College of Georgia
• Member, Epigenetics Society (formerly the DNA Methylation Society)
• Member, American Association for Cancer Research
• Member, American Society for Biochemistry and Molecular Biology
• Member, American Society for Microbiology

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