Department: Anatomy and Pathology
Research Cluster: Cancer Biology
Office: BBSC 336-V
Phone: (304) 696-3700
Iron is a nutrient required for several functions crucial to life. As such, iron levels may be manipulated to inhibit cell growth, restrict cell passage through the cell cycle, or even stimulate apoptosis. In addition to its requirement for cell growth, iron is a key mediator of oxidant stress. Iron donates electrons for the generation of the superoxide radical, and serves as both an electron donor and acceptor in the iron catalyzed Haber-Weiss reaction (Fenton chemistry) which generates hydroxyl radicals, and can also lead to the formation of ferryl radicals.1 Oxidant stress derived from iron can drive processes important to carcinogenesis, such as damage to DNA, mutagenesis, and stimulation of proliferation and inflammation.
Ferritin is the key cellular iron storage protein. Iron captured within ferritin does not generate the reactive radicals that it might otherwise form. We have developed a conditional transgenic mouse model where the generation of transgenic ferritin is tissue specific and temporally regulated. Our data demonstrate that transgenic induction of ferritin yields a phenotype of iron scarcity. Using this model, wherein we can manipulate iron at the cellular level, we hypothesize that we can impact the production of oxidant stress with tissue and temporal specificity.
The long term goal of our laboratory is to apply iron biology models to understand the role of oxidant stress in the etiology of chronic diseases, such as aging, atherosclerosis, cancer, kidney failure, and neurodegeneration. Current projects include:
- elucidating the role of oxidant stress and inflammation in lung carcinogenesis
- evaluation of the impact of iron sequestration in renal models of ischemia and acute failure
- determining the role of the liver labile iron pool in systemic iron regulation
- unraveling the mechanisms that regulate cellular and systemic ferritin trafficking respectively in vitro and in vivo.
Tissue culture models as well as mouse models will be used, thus you will be trained to work in vitro and in vivo. Techniques we employ include evaluation of gene expression by real-time PCR, northern and western blotting, genotyping using PCR and real-time PCR, biochemical assays to measure phase II enzyme activities, oxidant stress measurements (glutathione, protein carbonyl, 4-HNE and TBARs as endpoints), and iron evaluation (hematocrit, hemoglobin, total iron, non-heme iron). This laboratory uses team approaches to accomplish its goals, and thus I value individuals that can work together. Remember – the well executed experiment is all that stands between you and your bliss!
 Henle, E.S., and Linn, S. Formation, prevention, and repair of DNA damage by iron/hydrogen peroxide. J Biol. Chem. 272:19095-98, 1997.