Women's Faculty Association

Faculty Spotlight of the Women's Faculty Association (WFA)

Nancy Ratner, PhD, Receives $6.4 Million Grant

Groundbreaking research at Cincinnati Children's to understand the cause of a rare genetic disease called Neurofibromatosis 1 has led to the medical center being awarded a $6.4 million grant to look for possible treatments.

The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health (NIH), recently awarded the grant to Nancy Ratner, PhD, a researcher in the Division of Experimental Hematology and Cancer Biology, and director of the Neurofibromatosis Center at Cincinnati Children's Hospital Medical Center.

The grant is spread out over five years and will fund multiple research projects led by Dr. Ratner, the grant's principal investigator. The multi-disciplinary research projects - from basic scientific research to the testing of potential new therapies - include colleagues at Cincinnati Children's (John Perentesis, MD, FAAP and Timothy Cripe, MD, PhD), the University of Cincinnati (George Thomas, PhD and Sara Koozma, PhD) and the University of Minnesota (David Largaespada, PhD).

"Our long-term goal is to translate research findings into patient therapies," Dr. Ratner said. "Cincinnati Children's has an outstanding pediatric NF1 clinic with over 800 patients in its database. The medical center has participated in ongoing NF1 clinical trials, it's a leading center for pediatric anticancer drug development, and we bring together a world-class group of investigators who can identify drugs for treatment."

One out of every 3,000 people has neurofibromatosis type 1, a genetic disease that causes tumors to grow within nerves. Some tumors - called dermal neurofibromas – appear on the skin or just under the skin. Others - called plexiform neurofibromas - sprout within deeper nerves, and may press against the spinal cord, bones, muscles and organs. Neurofibromas can be surgically removed. However, total removal is often not possible because the tumors are heavily intertwined with nerve tissue. In rare cases when they become malignant, they can be targeted with chemotherapy or radiation, but in many cases the tumors cannot be eliminated. There is currently no treatment to prevent neurofibromas from growing. But in spite of the frequency and seriousness of neurofibromatosis, the disease has not gotten the attention it deserves until recently, in part because of research conducted by Ratner and other colleagues at Cincinnati Children's.

A study from Ratner's lab, published in the February 2008 issue of Cancer Cell, discovered that the timing of the NF1 gene mutation determines whether neurofibroma tumors will form. Ratner and her colleagues reported that if the NF1 gene mutated on day 12.5 of a mouse's embryonic development, neurofibroma tumors formed. If the gene mutated at other times during development, tumors did not form. The discovery was made using the first successful neurofibromatosis 1 mouse model, a mouse that Ratner's team genetically altered to mimic the disease that occurs in humans. "We now have a model of tumor formation that we can use to test therapies," explains Ratner.