The National Institutes of Health (NIH) recently awarded two five-year grants totaling more than $4 million to City of Hope cancer biology researchers. The grants support two studies: one that aims to understand how chemical and structural changes to DNA affect aging and another that will illuminate how ultraviolet, or UV, light contributes to cancer.

Gerd Pfeifer, Ph.D., Lester M. and Irene C. Finkelstein Chair in Biology and chair of the Department of Cancer Biology, is principal investigator for both grants.

Gerd Pfeifer received more than $4 million to advance epigenetics research. (Photo by Walter Urie)

DNA and aging

The National Institute on Aging awarded more than $2 million to support studies that seek to uncover epigenetic changes to cellular DNA during the aging process. Epigenetic changes are chemical modifications to DNA and chromosomes that can control how genes function.

Researchers have long pursued the key molecular source 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.”

Pfeifer will look for epigenetic changes to chromosomal DNA in cells as they age. His team also will look for answers in a special line of cells — those with a gene defect consistent with Cockayne syndrome, a rare, inherited condition.

People with Cockayne syndrome appear to age prematurely because their cells cannot perform a certain kind of DNA repair.

Pfeifer’s grant stems from the NIH’s Epigenomics Program, which focuses on the role of epigenomics, or epigenetic changes across the entire genome, in health and human disease.

“Epigenomics represents the next phase in our understanding of genetic regulation of health and disease,” said NIH Director Francis Collins, M.D., Ph.D.

The program is part of the NIH’s Roadmap for Medical Research.

UV light and cancer

The National Cancer Institute also renewed support for Pfeifer’s studies into the role of UV light in skin cancer development with a grant for more than $2 million. 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.

The team’s previous studies have examined how UV light damages DNA in chromosomes and how cells repair that damage. In 2008, the researchers 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.

Pfeifer will use funds from the renewed grant to find out 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.

“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.”