Marco Giovannini, M.D., Ph.D. - US grants

DESCRIPTION (provided by applicant): This application seeks partial support for the 2010 International Workshop on Neurofibromatosis Type 2, scheduled at the Bally's Hotel Conference Center, Las Vegas, NV, May 3-4, 2010. This meeting will be an international symposium for interaction and exchange among basic scientists and clinicians on NF2. Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the 8th cranial nerves. Significant morbidity, including deafness, can result from surgical treatment of these tumors. Meningiomas, ependymomas and other benign central nervous system tumors are also common in NF2. Despite the fact that significant progress has been made in our understanding of the biology of neurofibromatosis type 2 (NF2), patients with this disorder still face a poor clinical outcomes, significant morbidity and a decreased life span. The NF2 field is at a critical juncture and the goal of this conference is to provide a regular forum to bring together biologists, geneticists, clinicians, neurosurgeons, audiologists and others familiar with NF2 to share their latest basic and clinical research findings and experiences, with the ultimate goal to undertake international translational research projects and initiate NF2-specific targeted therapeutic trials. The Specific Aims of this proposal are (1) to provide a forum for the presentation and discussion of the latest and highest quality basic, clinical and auditory rehabilitation research on NF2, (2) to provide a meeting venue and atmosphere that is conductive to scientific discussion and brainstorming, and (3) to provide an opportunity for young investigators in the field to present their work and network with established investigators. Relevant questions to be discussed in this meeting are: 1. What Do We Know - and Don't Know - About NF2 Biology? 2. What is the natural history of NF2 tumors and its impact on clinical management? 3. Radio surgery and Radiotherapy for NF2 Tumors? 4. What is the Status of auditory rehabilitation in NF2 patients? 5. What is the Status of NF2 Preclinical Screening Tools? 6. What are Critical Endpoints in Evaluating NF2 Therapeutic Efficacy and Outcome? 7. What Are the Candidate Drugs and Potential Therapeutic Approaches for NF2? In addition there will be a special function honoring the career and contributions of Dr. William Hitselberger to acoustic neuroma and auditory brainstem implant surgical techniques. PUBLIC HEALTH RELEVANCE: This proposal seeks partial support for a conference on basic, clinical, auditory, and translational research on Neurofibromatosis type 2. This conference provides a unique forum for scientists, audiologists and clinicians to share their latest research results and to brainstorm about future directions in research.

DESCRIPTION (provided by applicant): Correlating otopathological analysis with genetic screening for existing syndromic and non-syndromic inner ear diseases is the goal of the House Ear Institute's contribution to the NIDCD's Otopathology Research Collaboration Network. The value of these correlations lies in connecting genetic diagnosis with a better understanding of disease progression and pathological sequelae, as well as the identification of targets for future treatment and, importantly, improved genetic counseling. Because of an almost complete lack of human biopsy material associated with inner ear disease, such connections remain largely unknown, and the only source of this information is the existing post-mortem temporal bone collections. For this reason, we have developed techniques for extracting and analyzing biological material (DNA and protein) from existing archival temporal bones for which relevant clinical data is cataloged and available. Here, we propose several Specific Aims designed to identify the underlying genetic mutations/genetic variants in existing temporal bone collections housed by members of our consortium, with the purpose of establishing a genotype/otopathology phenotype correlation. This has not been done consistently for any of the known genetic disorders of the inner ear, and the successful outcome of this proposal promises to provide an enhanced resource for the clinician and researcher who wish to link the etiology of inner ear disease with its otopathological outcome. PUBLIC HEALTH RELEVANCE: Molecular biological techniques have only recently been applied to study the correlation of biological structure with function in normal and diseased human temporal bones. This proposal will fill the knowledge gap by performing a comprehensive genotype-phenotype correlation in four hearing disorders;1) Hereditary, 2) Meniere's, 3) Otosclerosis, and 4) NF2.