The prevention and treatment of cancer is intimately linked to the cellular and organismal defense against oxygen-free radicals. These radicals can damage DNA, and if that damage occurs in critical target genes, can lead to mutations that contribute to cancer.  Dr. Torti's laboratory focuses on the regulation of key proteins that modify a cell's ability to generate damaging oxygen free radicals. Cellular iron is central to the ability to generate free radicals. Iron catalyzes the conversion of hydrogen peroxide into the hydroxyl radical, which then can directly damage cellular constituents. However, iron is not only toxic to cells, but is also essential for the function of enzymes that participate in numerous critical cellular processes.  These include cell cycling, reductive conversion of ribonucleotides to deoxyribonucleotides, electron transfer and others. Thus, iron homeostasis is tightly regulated. 

Ferritin is the primary intracellular iron-binding protein that limits free iron availability, and as such, is a critical mediator of cellular protection against free radical injury. Dr. Torti's laboratory has demonstrated the molecular details of the regulation of ferritin by inflammatory cytokines such as tumor necrosis factor (TNF) and IL-1 (interleukin-1). His lab has also elucidated the molecular basis of the ferritin regulation by pro-oxidant stress, including that induced by environmental toxins. The cellular and organismal consequences of ferritin dysregulation for cancer development are also areas of active research in Dr. Torti's laboratory. 

The field of chemoprevention is closely associated with iron biology. Chemopreventive agents target chemopreventive ferritin genes as well as other antioxidant response genes. The ability of oncogenes to perturb this process, such as Myc and EIA, are other areas of active laboratory investigation and suggest that the transformed phenotype harnesses and modifies cellular iron levels to enable vigorous cell growth and proliferation. Not only is ferritin important at a cellular and tissue level, but epidemiologic studies suggest the risk of developing cancer (as well as heart and neurodegenerative diseases) is increased in patients with high iron burdens. What fundamental biological mechanisms underlie this observation? Can the use of genetic testing for individual variation in levels of ferritin and other proteins of iron metabolism predict for cancer susceptibility? How does genetic variation link to environmental and dietary exposures? These are areas of active collaborations of the Torti lab and other laboratories at Wake Forest University.