Testing the Role of p21 Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease
Abstract
Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disease characterized by benign schwannomas that grow on the cranial and spinal nerves. While technically benign, the tumors are nonetheless progressive and relentless, usually resulting in death before age fifty from inoperable intracranial masses. To date, surgery remains the only effective therapy for these lesions, though this therapy is frequently associated with major morbidities, including loss of hearing. In this award we proposed to evaluate Group A Paks (Pak1 and Pak2) as a therapeutic target in NF2 by intercrossing Group A PAK deficient mice with our NF2 mouse model (PostnCre;Nf2flox/flox). Briefly, we hypothesized that the knockdown of Group A Paks in Nf2 deficient mice will rescue or reduce tumorigenesis. In Specific Aim 1, we proposed to characterize Paks signaling influence on NF2 in vivo by assessing hearing thresholds, survival rate, tumor formation and kinome analysis. In Specific Aim 2, we proposed to test Pak inhibitors in our NF2 tumor model in order to evaluate whether the inhibition of Pak rescues merlin function to wild-type levels by analyzing readouts generated from tumor growth and auditory brainstem response (ABR).
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2018
- Accession Number
- AD1062930
Entities
People
- Jonathan Chernoff
Organizations
- Fox Chase Cancer Center