Carver College of Medicine Profile

Dr. Buettner’s research focuses on the flow of electrons through chemical, biochemical, and biological systems and the consequences of changing the current in different biological circuits.  In mitochondria electrons flow through a high flux circuit efficiently producing ATP, and H₂O (respiration); however, some do not flow to dioxygen, rather just to NAD⁺ (glycolysis).  Of special interest is the flow of electrons into the many low flux biochemical circuits that partially reduce dioxygen producing superoxide and hydrogen peroxide.  Understanding quantitatively the elements of these circuits (e.g. antioxidants, redox enzymes, and proteins) and how they dictate the fundamental biology of cells and tissues and overall health of organisms is the primary goal.  Using this information to improve human health is the ultimate reward. 

Dr. Buettner’s goal is to understand the basic chemistry and biology of free radicals and related oxidants in human health and of course antioxidants, such as vitamins C and E, glutathione, as well as the enzyme systems that work in concert with these molecules. His 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); The ascorbate free radical as a marker of oxidative stress: An EPR study (PMID: 8384150); The concentration of glutathione in human erythrocytes is a heritable trait (PMID: 23938402).          

His basic research on vitamin C has lead to the hypothesis that ascorbate at pharmacological 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); Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer (PMID: 20068072).        

Nitric oxide as a membrane antioxidant. He has contributed to the understanding of fundamental chemistry of this small molecule functioning as an antioxidant; only 10-50 nano molar are needed serve this function. See: Nitric oxide as a cellular antioxidant: A little goes a long way (PMID: 16443165).        

He has 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. His work in this arena changed the working paradigm of redox biology. Examples are: The pecking order of free radicals and antioxidants: Lipid peroxidation, alpha-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.

Example Publications

Redox Biology Presentation:  In October, 2020, Dr Buettner presented the Sunrise Lecture at the annual meeting of the Radiation Research Society, Free radical biology: Its evolution and application.  This 32-minute video provides an overview of redox biology and how it is being applied to cancer therapy here at The University of Iowa.

(Complete List of Publications via Google Scholar or via National Library of Medicine)

Cushing CM, Petronek MS, Bodeker KL, Vollstedt S, Brown HA, Opat E, Hollenbeck NJ, Shanks T, Berg DJ, Smith BJ, Smith MC, Monga V, Furqan M, Howard MA, Greenlee JD, Mapuskar KA, St-Aubin J, Flynn RT, Cullen JJ, Buettner GR, Spitz DR, Buatti JM, Allen BG, Magnotta VA. 
Magnetic resonance imaging (MRI) of pharmacological ascorbate-induced iron redox state as a biomarker in subjects undergoing radio-chemotherapy.
Redox Biol. (2021) 38:101804. (Open Access) PMID: 33260088 
Link  http://doi.org/10.1016/j.redox.2020.101804