DUARTE, Calif., October 9, 2009 —The National Institutes of Health (NIH) recently awarded grants totaling more than $4 million to City of Hope for two five-year studies to examine how changes in DNA affect the aging process and to better understand the biological process of how sun exposure can lead to cancer. Gerd Pfeifer, Ph.D., Lester M. and Irene C. Finkelstein Chair in Biology and chair of the Department of Cancer Biology, City of Hope, is principal investigator for both studies.
Researchers have long pursued the key molecular cause of aging. Some theorize that unrepaired DNA damage simply builds up over time. Others trace aging to the oxidation of key molecules and other chemical stress. Scientists also tap the erosion of the ends of chromosomes — called telomeres — as a factor; some cite the loss of stem cells’ ability to renew tissue.
“It’s very likely that all of these play some part,” said Pfeifer. “We want to know if, and how, epigenetic changes are involved.”
Epigenetic changes are chemical modifications to DNA and chromosomes that can control how genes function. Pfeifer will look for epigenetic changes to chromosomal DNA in cells as they age. Pfeifer’s grant for more than $2 million was awarded by the NIH’s National Institute on Aging. His research will focus on the role of epigenomics, or epigenetic changes across the entire genome, in health and human disease.
The NIH’s National Cancer Institute renewed support for Pfeifer’s studies into the role of UV light in skin cancer development with a grant for more than $2 million. In 2008, his investigation showed conclusively that rays of UV-B light cause more thorough and lasting damage to DNA than UV-A, explaining why UV-B causes more skin cancers. Now in its second, five-year funding cycle, the award enables Pfeifer and colleagues to hunt down a direct, molecular connection — a cause and effect — between UV light and skin cancer.
“Although a great deal is understood about UV and skin damage,” said Pfeifer, “we’re hoping to further define the mechanisms behind that damage and how it can lead to melanoma.”
Pfeifer will use funds from the renewed grant to determine if UV light causes epigenetic changes that lead to melanoma. Melanoma is the most life-threatening type of skin cancer. Pfeifer and his team also want to know if, following exposure to UV light, cells repair active genes more quickly than inactive genes. If so, that may show how cells set priorities for their limited repair resources.