James Walker, Ph.D.
Center for Genomic Medicine, Mass General Research Institute
Assistant Professor of Neurology
Harvard Medical School
|PhD University of Cambridge 1997|
The Walker Laboratory at Massachusetts General Hospital focuses on the tumor-suppressor syndromes, neurofibromatosis type 1 (NF1) and schwannomatosis. Using a combination of genetic, molecular and biochemical approaches, we aim to identify new therapeutic targets for these diseases.
Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited tumor predisposition syndrome with an incidence of one in 3,000–4,000 people with no effective therapies currently. NF1 is a chronic multisystem disorder affecting many different tissues. Most adults with NF1 develop neurofibromas - benign, but often disfiguring, peripheral nerve associated tumors. About 10% of NF1 patients develop malignant peripheral nerve sheath tumors (MPNSTs), which carry a poor prognosis and are often fatal.
The NF1 gene encodes the protein neurofibromin, which functions as a negative regulator of RAS. Due to cell-specific complexities of RAS signaling, therapeutic approaches for NF1 will likely have to focus on a particular tissue and manifestation of the disease.
Familial schwannomatosis is a late-onset tumor predisposition disorder - clinically and genetically distinct from NF1 and NF2. Affecting 1 in 40,000 individuals, the disease is characterized by multiple peripheral nerve tumors, called schwannomas, and a predisposition to other nervous system tumors including meningiomas. Patients with schwannomatosis overwhelmingly present with intractable pain. Mutations in three genes are known to be involved in schwannomatosis: merlin (NF2), SMARCB1 and LZTR1.