Newswise — Neurofibromatoses (NF) is a set of genetic disorders causing the growth of tumors along nerves and even in brain, bones and skin. NF is classified into two types, called NF1 and NF2. NF2, sometimes referred to as Bilateral Acoustic NF (BAN), is mainly characterized as having tumors affecting both of the balance nerves which affect the hearing and balance function and often leads to profound deafness. Facial nerve paralysis also often occurs. A portion of NF2 patients also have meningiomas which are benign tumors of the covering (meninges) of the brain. Researchers at Columbus Children's Research Institute (CCRI) are studying NF2 to understand the underlying molecular mechanisms of tumor origin in an effort to determine if improved therapies for genetic manipulation or prevention of tumor growth may be possible. To assist with their research, the Department of Defense Congressionally Directed Neurofibromatosis Research Program recently awarded the CCRI team two research grants with a combined total cost of about 1.4 million dollars. The first grant is entitled, "Post-transcriptional Regulation of the Neurofibromatosis 2 Gene" , and the second grant is entitled, "The Role of Drosophilia Merlin in the Control of Mitosis Exit and Development."
"NF2 is associated with the neurofibromatosis 2 gene (NF2) which produces a tumor suppressor protein named "merlin" (named for moesin-ezrin-radixin like protein)," said Long-Sheng Chang, Ph.D., of the Columbus Children's Research Institute Center for Childhood Cancer and associate professor in the Department of Pediatrics, The Ohio State University, and the principal investigator in the study. "However, despite intense study of the NF2 tumor-suppressor, the mechanism by which merlin acts to prevent tumor formation is not well understood."
In the first study, Dr. Chang together with D. Bradley Welling, M.D., Ph.D., professor of Otolaryngology, The Ohio State University, and co-investigator of the project, examined vestibular schwannomas (also formerly called acoustic neuromas), frequently seen in NF2 patients. Schwannomas are tumors which grow from cells " called Schwann cells which cover the nerves throughout the body. They found that schwannomas produce aberrant messages from the NF2 gene, consequently generating abnormal NF2 proteins. Dr. Chang's team will use three molecular approaches to better understand the regulation of the NF2 gene at the RNA level. They plan to investigate whether such an abnormal regulation of NF2 expression is important for tumor formation. In the second study, Dr. Chang examined fruit flies (Drosophila melanogaster), which provides a genetic and developmental system that is easily tested and manipulated. The Drosophila gene, which resembles the human NF2 gene, been identified and shows a similar genetic code and functionality. Dr. Chang and his collaborators in the Siberian Division of Russian Academy of Sciences recently identified a new role for Drosophila merlin in the regulation of cell division, suggesting that regulation of cell division may be in part controlled by merlin. In addition, they also found that merlin is important for fly development. For the Idea Award, Dr. Chang's team will conduct a series of experiments to further examine the role of merlin in the control of cell division and development.
"NF2 is an extremely debilitating disease for those affected," said Dr. Welling, an internationally recognized otolaryngologist. Dr. Chang further added, "It is our hope that this research will lead to future studies examining the signal pathways that link merlin to intracellular signals regulating cell division. From there, new therapeutic regimens could be developed and used for the cure of NF2 tumors."
Columbus Children's Hospital ranks among the top 10 in National Institutes of Health research awards and grants to freestanding children's hospitals in the country. With nearly 500,000 patient visits each year, Children's Hospital is a 112-year-old pediatric healthcare network treating newborns through age 21. In 2003, the Columbus Children's Research Institute conducted more than 300 research projects and is the home of Centers of Emphasis encompassing gene therapy, molecular and human genetics; vaccines and immunity, childhood cancer, cell and vascular biology, developmental pharmacology and toxicology, injury research and policy, biopathology, microbial pathogenesis, and biobehavioral health. Pediatric Clinical Trials International (PCTI), a site management organization affiliated with the hospital, also coordinated more than 50 clinical trials. In addition to having one of the largest ambulatory programs in the country, Children's offers specialty programs and services. More than 75,000 consumers receive health and wellness education each year and affiliation agreements with nearly 100 institutions allow more than 1,700 students and 500 residents to receive training at Children's annually. More information on Children's Hospital of Columbus is available by calling (614) 722-KIDS (5437) or through the hospital's Web site at http://www.columbuschildrens.com.
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