Dr. Stewart studies phenotypes and genetic determinants of familial tumor-predisposition disorders. The goal of his work is to improve disorder-specific clinical care and cancer risk prediction, while translating insights garnered from rare disorders to a broader understanding of cancer occurrence.
Dr. Stewart's research focuses on neurofibromatosis type 1 (NF1), a common, monogenic disorder that dramatically increases the risk of various benign and malignant tumors in affected individuals. His research group established the association among a variety of novel NF1 phenotypes, including glomus tumors, gastrointestinal stromal tumors and pulmonary hypertension. Dr. Stewart's group is using genomic approaches to identify genetic modifiers of NF1, thereby uncovering genetic variation that influences phenotype severity (e.g., tumor burden and pigmentary differences). He sees patients with NF1, especially adults, to characterize novel and under-recognized tumor types associated with the disorder.
Dr. Stewart is leading a project which uses new high-throughput sequencing technologies to identify, catalog and characterize mutations in key "driver" genes in NF1-associated plexiform neurofibromas (PNs), congenital tumors affecting up to 50 percent of people with NF1. PNs can grow unpredictably and can be locally destructive. They are viewed as pre-malignant lesions from which malignant peripheral nerve sheath tumors, a type of soft-tissue sarcoma, arise.
Dr. Stewart is also the NIH principal investigator for a new natural history study on the DICER1-related pleuropulmonary blastoma (PPB) cancer predisposition syndrome. This disorder represents the first reported cancer predisposition syndrome due to altered microRNA biogenesis. Tumors associated with the disorder include pleuropulmonary blastoma, a rare childhood malignancy of the lung that arises during fetal lung development, as well as nephroblastoma, neuroblastoma and embryonal rhabdomyosarcoma and medulloblastoma. The purpose of the study is to better understand the phenotype and prevalent cancer rates in the disorder, develop evidence-based management guidelines for cancer prevention and to identify other associated genes (if any).
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last Updated: February 15, 2012