Dr. Briehl’s laboratory's is investigating the mechanisms by which the redox state of cancer cells causes resistance to therapy-induced apoptosis. Cellular redox state is determined by the sum of prooxidants (e.g., the levels of reactive oxygen species) and antioxidants (e.g., proteins like catalase and small molecules like vitamin E) in the cell. Cancer cells have frequently undergone changes consistent with an altered ability to handle oxidative stress. Genetic differences in proteins that protect cells against oxidative stress have been associated with an increased risk of cancer. Epidemiological studies suggest that a diet rich in fruits and vegetables confers a lower risk of cancer. One idea is that the high antioxidants content of fruits and vegetables is protective, although definitive studies to prove this have not yet been conducted. Another untested idea is that cancer patients should avoid taking antioxidant supplements while undergoing chemotherapy, as the antioxidants may oppose the action of the anticancer drugs.
Based on their research with model systems for lymphoma, breast and skin cancer, they have accumulated evidence that a cell's ability to handle oxidative stress influences its susceptibility to apoptosis. Lymphoma cells that have acquired resistance to oxidative stress simultaneously acquire resistance to chemotherapy-induced apoptosis. The basic metabolism of the resistant cells is also fundamentally altered. These findings clearly have implications for the development and treatment of cancer. They potentially have a broader impact, since dysregulation of apoptosis and cellular redox state are common to other major diseases.
Dr. Briehl’s laboratory is now working to determine how an altered cellular redox state contributes to the control of apoptotic signaling, and to identify molecules that sense oxidative stress, are involved in the mechanism of apoptosis and may be dysfunctional in cancer cells. Other research projects in the laboratory are: 1) using gene expression and tissue microarrays, and SNP analyses of lymphoma patient samples to investigate whether the expression of antioxidant enzymes predicts response to therapy; 2) exploring the use of novel redox-active agents as chemosensitizers in the treatment of lymphoma, and 3) testing these novel agents for their ability to prevent doxorubicin-induced cardiotoxicity.
Dr. Briehl is also involved in the Partnership for Native American Cancer Prevention. The partnership is between the Arizona Cancer Center at the University of Arizona, Northern Arizona University and Native American Nations in Arizona. The goal is to train more Native Americans for careers as cancer researchers. Dr. Briehl’s research project for the partnership is investigating the bioavailability and carcinogenicity of uranium from Navajo lands.