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Research interests
Dr. Anthony Pegg's research interests include polyamine metabolism and DNA repair research on the cellular physiology of polyamines.
Polyamines are small basic molecules essential for cell growth and differentiation. Their concentration is very tightly regulated within the cell and is altered by endocrine and other factors having trophic effects. The research is aimed at understanding metabolic pathways responsible for polyamine biosynthesis, degradation, and interconversion; factors responsible for regulating polyamine levels; polyamine roles in growth and differentiation; and design and application of specific inhibitors of polyamine production. Such inhibitors have already been shown to have potential therapeutic value and to be useful as research tools in studying polyamine function.
A second area of research concerns DNA repair enzymes' role in protecting against carcinogenesis by N-nitroso-compounds and other alkylating agents. An alkyltransferase, which removes alkyl groups from DNA, has been isolated and it has been shown that the level of this protein is both species and cell specific. There is a good correlation between the alkyltransferase content and resistance to carcinogenesis and mutagenesis by alkylating agents. Current research is aimed at studying the specificity of this system, factors controlling its activity, and investigating whether it is missing or reduced in certain hereditary conditions. Also, the possibility that transient inactivation of this DNA repair function can be used for cancer chemotherapy to augment the action of therapeutic alkylating agents is being investigated. A potent inhibitor, O6-benzylguanine, has been developed in Dr. Pegg's laboratory and in Phase 1 trials has been shown to be effective in depleting tumor cell alkyltransferase activity in patients with cancer. It is currently undergoing Phase 2 trials to determine its efficacy in improving chemotherapy.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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Projects
- 8 Finished
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INHIBITION OF DNA REPAIR TO ENHANCE CHEMOTHERAPY
Pegg, A., Dolan, E. M., Friedman, H. S., Gerson, S. L., Schold, N. S. C. & Pegg, A. E.
9/30/96 → 9/29/01
Project: Research project
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Alkyltransferase Inhibitors for Cancer Chemotherapy
Kanugula, S. & Pegg, A.
8/1/96 → 4/30/12
Project: Research project
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Introduction to the thematic minireview series: Sixty plus years of polyamine research
Pegg, A. E., Nov 30 2018, In: Journal of Biological Chemistry. 293, 48, p. 18681-18692 12 p.Research output: Contribution to journal › Review article › peer-review
Open Access22 Scopus citations -
Mammalian dna repair enzymes
Pegg, A. E. & Bennett, R. A., Jan 1 2018, Enzymes of Nucleic Acid Synthesis and Modification: Volume 1: DNA Enzymes. CRC Press, p. 179-205 27 p.Research output: Chapter in Book/Report/Conference proceeding › Chapter
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Polyamine metabolism and cancer: treatments, challenges and opportunities
Casero, R. A., Murray Stewart, T. & Pegg, A. E., Nov 1 2018, In: Nature Reviews Cancer. 18, 11, p. 681-695 15 p.Research output: Contribution to journal › Review article › peer-review
386 Scopus citations -
Unique Characteristics of the Parasite Polyamine Pathway
Pegg, A. E., Nov 6 2018, In: Structure. 26, 11, p. 1427-1429 3 p.Research output: Contribution to journal › Short survey › peer-review
Open Access1 Scopus citations -
Functions of polyamines in mammals
Pegg, A. E., Jul 15 2016, In: Journal of Biological Chemistry. 291, 29, p. 14904-14912 9 p.Research output: Contribution to journal › Review article › peer-review
Open Access404 Scopus citations