Faculty and Staff

Dr. Donald Andrew Burden

Associate Professor

Dr. Donald Andrew Burden
615-904-8194
Room 3083, Science Building (SCI)
MTSU Box 68, Murfreesboro, TN 37132

Degree Information

  • Ph.D., University of Louisville, KY (1993)
  • M.S., University of Louisville, KY (1989)
  • B.S., University of Louisville, KY (1987)

Areas of Expertise

  • Mechanism of Action of the Enzyme DNA Topoisomerase II
  • Mechanism of Action of Anticancer Drugs (DNA Topoisomerase II Poisons and Inhibitors)

Biography

Dr. Burden primarily teaches various biochemistry courses (CHEM 3530, CHEM 4500, CHEM 4510, CHEM 4520). His research interests include the mechanism of action of the enzyme DNA topoisomerase II, as well as the mechanism of action of the diverse group of anticancer drugs which target this enzyme. Dr. Burden was a Special Fellow of the Leukemia and Lymphoma Society(1998-2001), and was previously a Research Fellow in the laboratory of Dr. Neil Osheroff in the Dept. of Biochemistry at Vanderbilt ...

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Dr. Burden primarily teaches various biochemistry courses (CHEM 3530, CHEM 4500, CHEM 4510, CHEM 4520). His research interests include the mechanism of action of the enzyme DNA topoisomerase II, as well as the mechanism of action of the diverse group of anticancer drugs which target this enzyme. Dr. Burden was a Special Fellow of the Leukemia and Lymphoma Society(1998-2001), and was previously a Research Fellow in the laboratory of Dr. Neil Osheroff in the Dept. of Biochemistry at Vanderbilt University (1994-1999, 2001, 2003).

Dr. Burden enjoys music, reading, and military history ( particularly the American Civil War). He has four sons.

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Publications

  • Arivett, B., Farone, M., Masiragani, R., Burden, A., Judge, S., Osinloye, A., Minici, C., Degano, M., Robinson, M., and Kline, P. "Characterization of inosine-uridine nucleoside hydrolase (RihC) from Escherichia coli." Biochim. Biophys. Acta 1844, 656-662 (2014).
  • Bender, R.P., Lindsey, R.H., Burden, D.A., and Osheroff, N. "N-acetyl-p-benzoquinone imine, the toxic metabolite of acetaminophen, is a topoisomerase II poison." Biochemistry 43, 3731-3739 (2004).
  • Lovett, B...
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  • Arivett, B., Farone, M., Masiragani, R., Burden, A., Judge, S., Osinloye, A., Minici, C., Degano, M., Robinson, M., and Kline, P. "Characterization of inosine-uridine nucleoside hydrolase (RihC) from Escherichia coli." Biochim. Biophys. Acta 1844, 656-662 (2014).
  • Bender, R.P., Lindsey, R.H., Burden, D.A., and Osheroff, N. "N-acetyl-p-benzoquinone imine, the toxic metabolite of acetaminophen, is a topoisomerase II poison." Biochemistry 43, 3731-3739 (2004).
  • Lovett, B.D., Strumberg, D., Blair, I.A., Pang, S., Burden, D.A., Megonigal, M.D., Rappaport, E.F.,Rebbeck, T.R., Osheroff, N., Pommier, Y.G., and Felix, C.A. "Etoposide Metabolites Enhance DNA Topoisomerase II Cleavage Near Leukemia-Associated MLL Translocation Breakpoints." Biochemistry 40, 1159-1170 (2001).
  • Wilson Byl, J.A., Fortune, J.M., Burden, D.A., Nitiss, J.L., Utsugi, T., Yamada, Y., and Osheroff, N. "DNA topoisomerases as targets for the anticancer drug TAS-103: primary cellular target and DNA cleavage enhancement." Biochemistry 38, 15573-15579 (1999).
  • Kingma, P.S., Burden, D.A., and Osheroff, N. "Binding of Etoposide to Topoisomerase II in the Absence of DNA: Decreased Affinity as a Mechanism of Drug Resistance." Biochemistry 38, 3457-3461 (1999).
  • Burden, D.A., and Osheroff, N. "In Vitro Evolution of Preferred Topoisomerase II DNA Cleavage Sites." J. Biol. Chem. 274, 5227-5235 (1999).
  • Burden, D.A., and Osheroff, N. "Mechanism of Action of Eukaryotic Topoisomerase II and Drugs Targeted to the Enzyme." Biochim. Biophys. Acta 1400, 139-154 (1998).
  • Burden, D.A., Froelich-Ammon, S.J., and Osheroff, N. "Topoisomerase II-Mediated Cleavage of Plasmid DNA," Methods Mol. Biol. 95, 283-289 (2001).
  • Elsea, S.H., Westergaard, M., Burden, D.A., Lomenick, J.P., and Osheroff, N. "Quinolones Share a Common Interaction Domain on Topoisomerase II with Other DNA Cleavage-Enhancing Antineoplastic Drugs." Biochemistry 36, 2919-2924 (1997).
  • Burden, D.A., Kingma, P.S., Froelich-Ammon, S.J., Bjornsti, M.-A., Patchan, M.W., Thompson, R.B., and Osheroff, N. "Topoisomerase IIâ�¢Etoposide Interactions Direct the Formation of Drug-Induced Enzyme-DNA Cleavage Complexes." J. Biol. Chem. 271, 29238-29244 (1996).
  • Froelich-Ammon, S.J., Burden, D.A., Patchan, M.W., Elsea, S.H., Thompson, R.B., and Osheroff, N. "Increased Drug Affinity as the Mechanistic Basis for Drug Hypersensitivity of a Mutant Type II Topoisomerase." J. Biol. Chem. 270, 28018-28021 (1995).
  • Burden, D.A., and Sullivan, D.M. "Phosphorylation of the ï�¡- and Ã�-Isoforms of DNA Topoisomerase II is Qualitatively Different in Interphase and Mitosis in Chinese Hamster Ovary Cells." Biochemistry 33, 14651-14655 (1994).
  • Burden, D.A. "Modulation of DNA Topoisomerase II Activity by Phosphorylation in Chinese Hamster Ovary Cells During the Cell Cycle." Ph.D. dissertation, 1993.
  • Burden, D.A., Goldsmith, L.J., and Sullivan, D.M. "Cell cycle-dependent phosphorylation and activity of Chinese hamster ovary topoisomerase II." Biochem. J. 293, 297-304 (1993).
  • Burden, D.A. "Acid Phosphatase Activity in Cell-free Extracts of Pseudomonas putida" M.S. thesis, 1989.

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Research/Scholarly Activity

My area of primary interest is DNA topoisomerases. My doctoral dissertation research was on cell cycle-dependent phosphorylation of DNA topoisomerase II in Chinese hamster ovary cells, giving me years of experience in mammalian tissue culture, cell cycle studies, enzyme activity assays, and metabolic labeling using 32P. As a postdoctoral research fellow, I was involved in various studies of topoisomerase II and clinical and experimental drugs which target topoisomerase II. I have investigated...

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My area of primary interest is DNA topoisomerases. My doctoral dissertation research was on cell cycle-dependent phosphorylation of DNA topoisomerase II in Chinese hamster ovary cells, giving me years of experience in mammalian tissue culture, cell cycle studies, enzyme activity assays, and metabolic labeling using 32P. As a postdoctoral research fellow, I was involved in various studies of topoisomerase II and clinical and experimental drugs which target topoisomerase II. I have investigated why the enzyme cleaves DNA at the sequences where it acts, using both DNA cleavage mapping techniques as well as a SELEX approach for in vitro evolution of topoisomerase II DNA cleavage sites. I was also involved in work examining the interactions of drugs with the enzyme, and why different drugs induce the enzyme to cleave DNA at different sequences. In more recent years I have done some work on protein-protein interactions between topoisomerase II and histone deacetylases as well as topoisomerase II and retinoblastoma tumor suppressor protein. My current research is focusing on determining the mechanisms of inhibition of topoisomerase II by such compounds as tamoxifen, resveratrol, and gossypol. These experiments involve enzyme activity assays (relaxation of supercoiled DNA, decatenation of kinetoplast DNA, the ATPase activity of the enzyme, and its DNA binding), and I am now mainly studying the mechanism of gossypol. I know how gossypol affects the enzyme in the aforementioned assays, and need to do some additional controls before I can submit a manuscript with these results (hopefully by the end of 2013). I strongly suspect that gossypol is covalently modifying the enzyme, and have begun GC-MS/MS experiments to identify any sites of attachment of gossypol to the enzyme. Future projects with gossypol include characterizing cotton topoisomerase II to see if it is inherently resistant to gossypol (this will involve cloning the cotton topoisomerase II gene and/or purification of the enzyme from plant material), examining cotton predators to see if any have forms of the enzyme inherently resistant to gossypol, making gossypol-resistant mutants of the human enzyme to further characterize the interactions of the drug with the enzyme, and determining the possible involvement of gossypol in inhibition of meiosis (topoisomerase II is required for meiosis, and gossypol is a male contraceptive). Once I am experienced in GC-MS/MS analysis of topoisomerase II, I would also like to compare post-translational modifications of the human enzyme overexpressed in and purified from yeast (which is by far the most common source of the enzyme) vs. the constitutively expressed enzyme from human cells. This may be useful in identifying previously unsuspected limits on the applicability of results obtained using the recombinant enzyme.

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