Garry Buettner, PhD
Introduction
Dr. Buettner's research focuses on the basic chemistry and biology of free radicals and related oxidants in human health. His research program touches on many themes that include: The fundamental chemistry and biochemistry of vitamins C and E and other small molecular weight antioxidants. Work from his laboratory has played a major role in establishing the current paradigm of how these antioxidants function. This work has provided a new view of ascorbate as the terminal, small molecule, water-soluble antioxidant. See: The pecking order of free radicals and antioxidants: Lipid peroxidation, -tocopherol, and ascorbate. PMID: 8434935 and The ascorbate free radical as a marker of oxidative stress: An EPR study. PMID: 8384150.
Our work on ascorbate has lead to the hypothesis that ascorbate at physiological concentrations can be used as a pro-drug for the delivery of hydrogen peroxide to tumor cells and thereby serve as a component of the therapy of certain cancers. See: Ascorbic acid at pharmacologic concentrations selectively kills cancer cells: ascorbic acid as a pro-drug for hydrogen peroxide delivery to tissues. PMID: 16157892 and Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. PMID: 20068072.
Nitric Oxide as a membrane antioxidant. We have contributed to the understanding of fundamental chemistry of this small molecule functioning as and antioxidant. We have found that levels of only 10-50 micro molar are needed serve this function. See: Nitric oxide as a cellular antioxidant: A little goes a long way. PMID: 16443165.
We have initiated the new research field of Quantitative Redox Biology. This represents a transition from understanding basic biology of cells and tissues at an observational level to a true mechanistic level. Our work in this arena changed the working paradigm of redox biology. Examples are: The pecking order of free radicals and antioxidants: Lipid peroxidation, -tocopherol, and ascorbate. PMID: 8434935; Redox state of the cell as viewed though the glutathione disulfide/glutathione couple. PMID: 11368918; and A new paradigm: Manganese superoxide dismutase influences the production of H2O2 in cells and thereby their biological state. PMID: 17015180.
The primary goal of our research program is: to do some good.
Current Positions
- Professor of Radiation Oncology
- Director, ESR Facility
Education
- BA in Chemistry, University of Northern Iowa
- MS in Chemistry, The University of Iowa
- PhD in Chemistry, The University of Iowa
- Fellow in Radiation Research Lab, The University of Iowa
- Fellow, NRSA, NIH/NIEHS North Carolina
Graduate Program Affiliations
Center, Program and Institute Affiliations
Research Interests
- Research Interests free radical, nitric oxide, ascorbic acid, tocopherol, vitamin C, vitamin E, redox biology, superoxide, hydrogen peroxide, electron spin resonance, EPR, ESR
- Research Summary
Selected Publications
- Carroll RS, Buettner GR, Cullen JJ. (2021) Chapter 46 - Pharmacological ascorbate and use in pancreatic cancer, in Cancer (Second Edition), Editor(s): Preedy VR, Patel VB. Academic Press, pp 515-521, ISBN 9780128195475, https://doi.org/10.1016/B978-0-12-819547-5.00046-8.
- Wagner BA, Buettner GR. (2023) Stability of aqueous solutions of ascorbate for basic research and for intravenous administration. Adv Redox Res. 9:100077. https://doi.org/10.1016/j.arres.2023.100077 PMID: 37808406; PMCID: PMC10552410
- Du J, Filipović MR, Wagner BA, Buettner GR. (2023) Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide. Adv Redox Res. 9:100079. https://doi.org/10.1016/j.arres.2023.100079 PMID: 37692975 PMCID: PMC10486277.
- Petronek MS, Monga V, Bodeker KL, Kwofie M, Lee CY, Mapuskar KA, Stolwijk JM, Zaher A, Wagner BA, Smith MC, Vollstedt S, Brown H, Chandler ML, Lorack AC, Wulfekuhle JS, Sarkaria JN, Flynn RT, Greenlee JDW, Howard MA, Smith BJ, Jones KA, Buettner GR, Cullen JJ, St-Aubin J, Buatti JM, Magnotta VA, Spitz DR, Allen BG. Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM. Clin Cancer Res. 2024 Jan 17;30(2):283-293. doi: 10.1158/1078-0432.CCR-22-3952. PMID: 37773633.
- Steers GJ, O'Leary BR, Du J, Wagner BA, Carroll RS, Domann FE, Goswami PC, Buettner GR, Cullen JJ. (2023) Pharmacologic Ascorbate and DNMT Inhibitors Increase DUOX Expression and Peroxide-Mediated Toxicity in Pancreatic Cancer. Antioxidants (Basel). 12(9):1683. http://doi.org/10.3390/antiox12091683 PMID: 37759986; PMCID: PMC10525653
- Carroll RS, Du J, O'Leary BR, Steers G, Goswami PC, Buettner GR, Cullen JJ. (2023) Pharmacological ascorbate induces sustained mitochondrial dysfunction. Free Radic Biol Med. 204:108-117. http://doi.org/10.1016/j.freeradbiomed.2023.04.023 PMID:37137343; PMCID:PMC10375417
- Degtyareva NP, Placentra VC, Gabel SA, Klimczak LJ, Gordenin DA, Wagner BA, Buettner GR, Mueller GA, Smirnova TI, Doetsch PW. (2023) Changes in metabolic landscapes shape divergent but distinct mutational signatures and cytotoxic consequences of redox stress. Nucleic Acids Res. 20:gkad305. http://doi.org/10.1093/nar/gkad305 PMID: 37078607; PMCID:PMC10250236.
- Petronek MS, Teferi N, Caster JM, Stolwijk JM, Zaher A, Buatti JM, Hasan D, Wafa EI, Salem AK, Gillan EG, St-Aubin JJ, Buettner GR, Spitz DR, Magnotta VA, Allen BG. (2023) Magnetite nanoparticles as a kinetically favorable source of iron to enhance GBM response to chemoradiosensitization with pharmacological ascorbate. Redox Biol. 62:102651. http://doi.org/10.1016/j.redox.2023.102651 PMID:36924683; PMCID:PMC10025281.
- Du J, Pope AN, O'Leary BR, Wagner BA, Goswami PC, Buettner GR, Cullen JJ. (2022) The role of mitochondria in pharmacological ascorbate-induced toxicity. Sci Rep. 12(1):22521. http://doi.org/10.1038/s41598-022-27185-9 PMID:36581766; PMCID:PMC9800562.
- O'Leary BR, Ruppenkamp EK, Steers GJ, Du J, Carroll RS, Wagner BA, Buettner GR, Cullen JJ. (2022) Pharmacological Ascorbate Enhances Chemotherapies in Pancreatic Ductal Adenocarcinoma. Pancreas. 51(6):684-693. http://doi.org/10.1097/MPA.0000000000002086 PMID:36099493; PMCID:PMC9547864.