Mutations in the NF1 tumor suppressor gene cause the common genetic disorder neurofibromatosis type 1 (NF1). Neurofibromin, the protein product of the NF1 gene, negatively regulates Ras by accelerating the intrinsic GTPase activity of Ras and converting Ras-GTP to Ras-GDP. Individuals with NF1 have a range of malignant and nonmalignant manifestations that involve the peripheral and central nervous system, blood cells, and skeletal malformations. Recent studies in our lab and others have provided genetic evidence that loss of a single allele of NF1 is sufficient to alter Ras activity and cell fates in a range of tissues. Work in my laboratory is focused on understanding the role of lineages within the tumor microenvironment in promoting the progression of the cutaneous and plexiform neurofibromas that are the hallmark of neurofibromatosis type 1. Other studies in the laboratory are focused on evaluating the pathogenesis of the skeletal dysplasias that afflict a range of infants, children, and adults with neurofibromatosis type 1. A particular emphasis is focused on identifying key biochemical targets that influence these pathological processes.
Cancer stem cells with a particular interest in neurofibromatosis type 1.