Julia Brumaghim
Associate Professor
Bioinorganic Chemistry
Phone: (864) 656-0481
Office: 481 Hunter Laboratories
E-mail: brumagh@clemson.edu
Research Interests | Publications | Research Group
Dr. Brumaghim earned her A.B. degree in chemistry from Harvard University in 1994. Her Ph.D. work with Prof. Greg Girolami at the University of Illinois at Urbana-Champaign involved the synthesis of air-sensitive osmium complexes. After graduation in 1999, she was an NIH postdoctoral fellow with Prof. Ken Raymond at the University of California, Berkeley (1999-2001), studying chiral bioinorganic and supramolecular coordination chemistry. She then joined Prof. Stuart Linn's lab in the molecular and cellular biology department at Berkeley to conduct postdoctoral research in the biochemistry of DNA damage and iron interactions with NAD(P)H (2001-2003) before joining the faculty at Clemson University in 2003.
Research Interests
Research in the Brumaghim group aims to understand how metal ions form oxygen radical species that damage DNA and cause cell death, and how antioxidants prevent this damage. Studying DNA damage inhibition by antioxidants may lead to future treatments for cancer and other diseases caused by oxidative damage. Research projects combine areas of coordination chemistry, biochemistry, and toxicology. Because of the diversity of research areas, students will develop skills in both inorganic chemistry and the biochemistry of nucleic acids and oxidative DNA damage.
How do antioxidants prevent DNA damage and cell death?
In cells, Fe2+ and Cu+ react with hydrogen peroxide (H2O2) to form hydroxyl radical (•OH), a highly reactive species that damages DNA. This DNA damage is an underlying cause of neurodegenerative and cardiovascular diseases, as well as many cancers. Antioxidants prevent hydroxyl radical from damaging DNA, and are of interest to treat and prevent these diseases.
Selenium and sulfur compounds are well-known antioxidants. In fact, patients given selenium supplements in one ten-year clinical trials had 50% fewer total incidences of cancer. The goal of our research is to provide a chemical explanation for clinical observations of selenium and sulfur antioxidant activity. Using gel electrophoresis, we recently discovered that sulfur and selenium antioxidants prevent metal-mediated DNA damage through metal coordination. Currently we are interested in testing a variety of antioxidants to determine what chemical features lead to better DNA damage prevention. Understanding this novel mechanism of antioxidant activity will aid the design of more potent antioxidant compounds.
Because we found that antioxidants prevent DNA damage in vitro by metal coordination, we are also interested in testing antioxidant ability to prevent cell death under oxidative stress. When cells (both bacterial and mammalian) are exposed to H2O2, many die due to the DNA damage from iron-generated hydroxyl radical. We are currently testing antioxidants that prevent DNA damage for their ability to prevent cell death upon H2O2 challenge.
What is the role of metal coordination in antioxidant activity?
Since metal coordination by selenium and sulfur is a factor in antioxidant activity, we are interested in synthesizing metal-selenolate and -thiolate complexes. With these complexes, we are studying the effects of M-Se or M-S coordination on Fe2+/3+ or Cu+/2+ redox potentials and reactivity with H2O2. Results from these experiments will allow us to determine mechanisms for antioxidant activity of selenium and sulfur compounds.
To synthesize our target selenolate and thiolate metal complexes, we use nitrogen donor ligands such as Tp* and Tpm* (tris(3,5-dimethyl- pyrazolyl)borate and –methane, respectively) ligands to coordinate iron. These starting complexes have exchangeable solvato ligands: [LFe(H2O)3]n+ and LFe(CH3CN)3]n+ (L=Tp*, n=1; L=Tpm*, n=2). We are currently interested in synthesizing new ligands as well as synthesizing and characterizing our target complexes by NMR, X-ray crystallography, and cyclic voltammetry.
Joining the Brumaghim group:
Undergraduate and graduate researchers. To set up an appointment, please send an email with your academic and/or research background as well as the area(s) of research that interest you. Students of all levels and backgrounds are encouraged to apply.
Postdoctoral researchers. Please send an application by regular mail or email with your CV (including academic and research background), a publication list, and the names and contact information of three references. Also indicate the area(s) of research that most interest you. Incomplete applications may not be considered.
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Publications
Battin, E. B.; Brumaghim, J. L. “Metal Specificity in DNA Damage Prevention by Sulfur Antioxidants,” J. Inorg. Biochem. 2008, in press.
Perron, N. R; Hodges, J. N.; Jenkins, M.; Brumaghim, J. L. “Prediciting How Polyphenol Antioxidants Prevent DNA Damage by Binding to Iron,” Inorg. Chem. 2008, 47, 6153-6161.
Ramoutar, R. R.; Brumaghim, J. L. “Investigating the Antioxidant Properties of Oxo-Sulfur Compounds on Metal-Mediated DNA Damage,” Main Group Chem. 2007, 101, 1028-1035.
Ramoutar, R. R.; Brumaghim, J. L. “Effects of Inorganic Selenium Compounds on Oxidative DNA Damage,” J. Inorg. Biochem. 2007, 101, 1028-1035.
Battin, E. E.; Perron, N. R.; Brumaghim, J. L. “The Central Role of Metal Ion Coordination in Selenium Antioxidant Activity,” Inorg. Chem. 2006, 45, 499-501.
Brumaghim, J. L.; Michels, M.; Pagliero, D; Raymond, K. N. “Encapsulation and stabilization of reactive aromatic diazonium ions and the tropylium ion within a supramolecular host.” Eur. J. Org. Chem. 2004, 5115-5118.
Brumaghim, J. L.; Michels, M.; Raymond, K. N. “Hydrophobic chemistry in aqueous solution: Stabilization and stereoselective encapsulation of phosphonium guests in a supramolecular host.” Eur. J. Org. Chem. 2004, 4552-4559.
Fiedler, D.; Pagliero, D; Brumaghim, J. L.; Bergman, R. G.; Raymond, K. N. “Encapsulation of Cationic Ruthenium Complexes into a Chiral Self-Assembled Cage,” Inorg. Chem. 2004, 43, 846-848.
Brumaghim, J. L.; Li, Y.; Henle, E.; Linn, S. “Effects of hydrogen peroxide upon nicotinamide nucleotide metabolism in Escherichia coli: Changes in enzyme levels and nicotinamide nucleotide pools and studies of the oxidation of NAD(P)H by Fe(III),” J. Biol. Chem. 2003, 278, 42495-42504.
Brumaghim, J. L.; Raymond, K. N. “What Should Be Impossible: Resolution of the Mononuclear Gallium Coordination Complex, Tris(benzohydroxamato)gallium(III).” J. Am. Chem. Soc. 2003, 125, 12066-12067.
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