Research Focus
We are interested in the function of the NF2 tumor suppressor gene, mutated in patients with neurofibromatosis type 2 (NF2) with the goal of providing novel therapeutic options to patients. NF2 is an often devastating autosomal dominant disorder which, until relatively recently, was confused with its more common namesake neurofibromatosis type 1. Subjects who inherit a mutated allele of the NF2 gene inevitably develop schwannomas, affecting particularly the superior vestibular branch of the 8th cranial nerve, usually bilaterally. Meningiomas and other benign central nervous system tumours such as ependymomas are other common features.
The NF2 tumor-suppressor gene was cloned more than a decade ago, but the function of its encoded protein, Schwannomin/Merlin, remains elusive. Like the closely related ERM proteins, NF2 appears to provide regulated linkage between membrane-associated proteins and the actin cytoskeleton and is therefore poised to function in receiving and interpreting signals from the extracellular milieu. Recent studies suggest that the NF2 protein may coordinate the processes of growth-factor receptor signaling and cell adhesion. Varying use of this organizing activity by different types of cells could provide an explanation for the unique spectrum of tumors associated with NF2 deficiency.
The lack of satisfactory treatments for NF2-related tumors represents a significant unmet medical need for NF2 patients. Our strategy for the identification of the possible mechanism of action of the NF2 gene product is largely based on mouse modeling and the study of human tumors. Our goal is to find drugs that will improve the treatment and long-term survival of NF2 patients, and ultimately provide them with a better quality of life.