The Steensma Laboratory conducts research that aims to develop new treatment strategies for sarcomas. Specifically, the lab is interested in determining the mechanisms underlying tumor formation in sporadic bone and soft tissue sarcomas and in neurofibromatosis type 1, a hereditary disorder caused by mutations in the neurofibromin 1 (NF1) gene. Neurofibromin is considered to be a tumor suppressor that suppresses Ras activity by promoting Ras GTP hydrolysis to GDP. People with mutations in the neurofibromin 1 gene develop benign tumors called neurofibromas and have an elevated risk of malignancies ranging from solid tumors to leukemia, including highly aggressive sarcomas. The disease affects 1 in 3000 people in the United States, of whom 8–13% will ultimately develop a neurofibromatosis-related sarcoma in their lifetime. These aggressive tumors typically arise from benign neurofibromas, but the process of benign to malignant transformation is not well understood and treatment options are limited, leading to poor five-year survival rates.
Our current sarcoma-related research efforts include the development of genetically engineered mouse models of neurofibromatosis type 1 tumor progression; the identification of targetable patterns of intra- and intertumoral heterogeneity through next-gen sequencing; genotype-phenotype correlations in neurofibromatosis type 1 and related diseases; and mechanisms of chemotherapy resistance in bone and soft-tissue sarcomas.