Human health and risk for disease ultimately depend on the integrity of our DNA, the genetic material that provides the body’s blueprint for manufacturing proteins that carry out the function of cells and organs. Aberrant forms of DNA can produce inherited diseases, and changes in DNA during life are believed to trigger cancer and many other chronic diseases. Such changes can result from exposure to certain chemicals found in the workplace and others in the diet and medications, and to sunlight in outdoor workers. Two broad types of DNA changes are recognized: DNA damage and DNA silencing. Our research is focused on the mechanisms that can lead to prevention and therapeutic strategies for reversing DNA damage relevant to the workplace.
• Insights Into Mechanisms that Lead to Cancer
The causes and treatment of cancer are important to Oregon workers because some workplace exposures can cause cancer. Moreover, cancer is a disease that will strike a significant number of workers at some point during their career. Work in the Turker laboratory is focused on the underlying causes of cancer at the level of gene and chromosome defects and on “gene silencing”, which causes genes that should be expressed to turn off inappropriately.
• Enhancing the Effectiveness of Chemotherapeutic Protocols
Cancer is the second leading cause of death in the United States, with over 1,500,000 new cases reported in 2010, a figure that does not include the 1,300,000 new cases of non-melanoma skin cancers diagnosed each year. Lifetime probabilities of having cancer are nearly 50% for men and 35% for women, and this results in greater than 600,000 deaths in the United States each year, nearly 25 percent of all deaths. The nationwide costs for treating and managing these diseases are estimated to be in excess of $264 billion per year. In 2010, more than 21,000 Oregonians were diagnosed with a new cancer and more than 7,500 died as a direct result of these diseases. Many of these cancers are at least partially the result of environmental toxicant exposures (found in the workplace), making their prevention and effective treatments a high priority for research in the Lloyd laboratory. A major focus in the laboratory has been to identify more effective cancer treatments that use chemotherapeutic agents.
• Novel Therapeutic Strategy for the Prevention of Skin Cancer
Ultraviolet (UV) light (in sunlight) causes DNA damage in skin cells, leading to more than one million cases of non-melanoma skin cancer diagnosed annually in the United States. Human cells possess only one mechanism to repair UV-induced DNA damage, and lack a DNA enzyme that can specifically initiate an alternative DNA repair pathway that is present in other organisms. Certain bacteria and viruses have very efficient systems for the repair of sunlight-induced DNA damage. The McCullough and Lloyd laboratories have identified a DNA repair enzyme from a virus that infects single cell green algae, Chlorella virus PBCV-1, and have engineered this enzyme to contain a nuclear localization sequence (NLS) and a membrane permeabilization peptide (TAT) for enhanced delivery to human skin cells. Drs. Lloyd and McCullough currently have multiple patents either awarded, or in review, for the application of this enzyme and related enzymes in the prevention of skin cancer.
See the Oregon Institute of Occupational Health Sciences' recent accomplishments of this program, or
See the Oregon Institute of Occupational Health Sciences' Research page to link to the research of the scientists working in this area:
Stephen Lloyd, PhD
Amanda McCullough, PhD
Mitch Turker, PhD