About
Brumaghim earned her Ph.D. in inorganic chemistry from the University of Illinois at Urbana-Champaign. She then completed an NIH post-doctoral fellowship with Dr. Ken Raymond in the Department of Chemistry at the University of California at Berkeley in bioinorganic chemistry, followed by a second post-doctoral appointment with Dr. Stuart Linn in the Department of Molecular and Cellular Biology in DNA damage and repair, also at Berkeley. At Clemson University, Dr. Brumaghim had examined the ability of a variety of antioxidant classes to prevent metal-mediated oxidative damage. This oxidative damage is responsible for cell death during oxidative stress and leads to a wide variety of pathologies, including cardiovascular disease, cancer, and neurodegenerative diseases. However, due to the lack of readily deployable tools to study such damage and a lack of understanding about cellular metal-based processes, metal-mediated oxidative DNA damage is often overlooked for other, easier-to-study pathways. Dr. Brumaghim has developed tools to quantify antioxidant prevention of metal-mediated oxidative damage, and has demonstrated the first quantitatively predictive, structure-activity relationships for a variety of different antioxidant classes. She has also extended this work to explore mechanism of nanoparticle toxicity and the ability of antioxidants to prevent this, effects of plastics additives on cellular reactive oxygen species and differentiation, and mechanisms of antifungal drug resistance related to metal binding, reactive oxygen species generation, and DNA instability.
Visit Dr. Brumaghim's Department Profile.
How their research is transforming health care
The potential of antioxidants for treating, and more importantly preventing, disease is widely recognized, but antioxidants have not proven decisively useful in clinical trials. One reason for this is that tens of thousands of antioxidants are known and testing even a significant fraction of those in clinical trials is practically impossible. Dr. Brumaghim was the first to identify a new mechanism for the antioxidant activity of several antioxidant classes (prevention of metal-mediated DNA damage) and to establish predictive models for their activity. These models have been validated in biochemical assays and bacterial cells, and initial results seem to confirm these models in human cell cultures as well. The results of Dr. Brumaghim’s research has strongly suggested why several NIH-funded clinical trials (totaling > $100,000,000 spent) of selenium antioxidants have failed. In addition, the ability of many classes of drugs to bind metals and generate DNA-damaging reactive oxygen species has been overlooked as a mechanism for development of drug resistance. It is her sincere hope that rationally selected antioxidants will be used in future, mechanistically sound clinical trials that could transform the prevention of diseases caused by oxidative stress, such as cancer, cardiovascular disease, and neurodegenerative diseases. She also hopes her work will spur investigations of metal binding as a possible mechanism for drug resistance.
Health Research Expertise Keywords
Faculty Scholar, Antioxidants, Metals, Oxidative damage, DNA damage, Iron, Copper, Selenium, Sulfur, Polyphenols, Nanoparticles, Fluconazole, Glutathione
