David Finger is fighting premature aging.
The 31-year-old post-doctoral fellow in the Department of Radiation Biology isn’t concerned about his own aging, but rather that caused by Werner syndrome. Finger, Ph.D., recently received the Ruth L. Kirschstein Individual National Research Service Award Fellowship from the National Institutes of Health (NIH) to study a protein involved in the genetic disease. The award provides $360,000 of funding over three years.
Werner syndrome, also called progeria of the adult, is rare, occurring in one of every 1 million people. Symptoms, which usually manifest between the ages of 30 and 40, include signs of extreme aging such as wrinkled skin, baldness, cataracts, muscular atrophy and a tendency to diabetes mellitus, among others.
Past research has identified the gene for Werner syndrome, which produces a type of enzyme called a helicase. Helicases unzip and unwind the DNA double helix during replication (when more copies of DNA are made), transcription (when the cell translates the genetic code into protein) and repair. Mutations in the Werner gene cause vast instability in the genome, which leads to the symptoms of Werner syndrome and can cause age-associated diseases, such as cancer, type 2 diabetes and Alzheimer’s disease.
Finger, a structural biologist, is seeking to understand how the Werner gene product, called WRN, interacts with another protein called FEN-1, which repairs DNA. “WRN physically couples with FEN-1,” forming a complex that makes FEN-1 more effective at repairing damaged DNA, said Finger. “We’re trying to figure out what exactly occurs to stimulate FEN-1.”
Department Director Binghui Shen, Ph.D., has done extensive work characterizing FEN-1 and its function in the cell. Though Werner syndrome is rare, Shen notes that “cancer and aging are related. David’s work is important to helping us understand how WRN and FEN-1 work together to repair DNA,” and this has strong implications not just for the relatively few victims of Werner syndrome, but for understanding how cancer, diabetes and other age-associated diseases might develop.
Shen, who serves as Finger’s mentor as required by the Kirschstein fellowship, expressed a great deal of pride in Finger’s obtaining the prestigious award. “As more postdocs get federal funds, this will have a very positive impact on City of Hope,” he said.
Finger obtained his doctorate from the University of California, Los Angeles, prior to joining City of Hope in 2004. In addition to Shen and other members of the department, Finger’s collaborators on the WRN project include John Tainer, Ph.D., and Jefferson Perry, Ph.D., of The Scripps Research Institute in La Jolla, Calif.
The Ruth L. Kirschstein Individual National Research Service Award supports individuals with a doctoral degree for a three-year period of supervised research experience to achieve independence. The award is named for Ruth Kirchstein, M.D., deputy director of the NIH.