Adjunct Investigator

Genetic Disease Research Branch

Education

B.A. Vassar College, 1992

M.D. University of Pennsylvania School of Medicine, 1998

Biography

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).

Publications

Stewart DR, Huang A, Zackai EH, Anderlid BM, Medne L, Russell K, Kaur M, Rossi E, Tenconi R, Nordenskjöld M, Gripp K, Nicholson L, Meschino WS, Capua E, Quarrell OWJ, Flint J, Irons M, Giampietro PF, Schowalter DB, Zeleski CA, Malacarre M, Faravelli F, Spinner NB, Krantz ID. Subtelomeric deletions of chromosome 9q: A novel microdeletion syndrome. American Journal of Medical Genetics, 128A (4): 340-351. 2004. [PubMed]

Ho CKM, Wood JR, Stewart DR, Ewens K, Ankener W, Wickenheisser J, Nelson-Delgrave V, Zhang Z, Legro RS, Dunaif A, McAllister JM, Spielman R, Strauss, JF. Increased transcription and increased mRNA stability contribute to increased GATA6 mRNA abundance in PCOS theca cells. Journal of Clinical Endocrinology and Metabolism, 90 (12): 6596-6602. 2005. [PubMed]

Stewart DR, Dombroski B, Urbanek M, Ankener W, Ewens KE, Wood JR, Legro RS, Strauss JF, Dunaif A, Spielman RS. Fine mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity. Journal of Clinical Endocrinology and Metabolism, 91 (10): 4112-4117. 2006. [PubMed]

Stewart DR, Corless CL, Rubin BP, Heinrich MC, Messiaen LM, Kessler LJ, Zhang PJ, Brooks DG. Mitotic recombination as evidence of alternative pathogenesis of gastrointestinal stromal tumors (GISTs) in neurofibromatosis type 1. Journal of Medical Genetics, 44: e61. 2007. [PubMed]

Stewart DR, Cogan JD, Kramer MR, Miller WT Jr., Christiansen LE, Pauciulo MW, Messiaen LM, Tu GS, Thompson WH, Pyeritz RE, Ryo JH, Nichols WC, Kodama M, Meyrick BO, Ross DJ. Is pulmonary arterial hypertension in neurofibromatosis type 1 secondary to a plexogenic arteriopathy? Chest, 132 (3): 798-808. 2007. [PubMed]

Stewart DR and Kleefstra T. The chromosome 9q subtelomere deletion syndrome. American Journal of Medical Genetics Part C Seminar in Medical Genetics, 145C: 383-392. 2007. [PubMed]

Boley S, Sloan JL, Pemov A, Stewart DR. A quantitative assessment of the burden and distribution of Lisch nodules in adults with neurofibromatosis type 1. Investigative Ophthalmology and Visual Science, 50: 5035-5043. 2009. [PubMed]

Brems H, Park C, Maertens O, Pemov A, Messiaen L, Upadhyaya M, Claes K, Beert E, Peeters K, Mautner V, Sloan JL, Yao L, Lee CR, Sciot R, De Smet L, Legius E, Stewart DR. Glomus tumors in neurofibromatosis type 1: genetic, functional and clinical evidence of a novel association. Cancer Research, 69 (18): 7393-7401. 2009. [PubMed]

Pemov A, Park C, Reilly KM, Stewart DR. Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency. BMC Genomics, 11(1): 194. 2010. [PubMed]

Ewens KG, Stewart DR, Ankener W, Urbanek M, McAllister JM, Chen C, Baig KM, Parker SCJ, Margulies EH, Legro RS, Duanif A, Strauss JF, Spielman RS (posthumously). Family-based analysis of candidate genes for polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism, 95(5): 2306-2315. 2010. [PubMed]

Stewart DR, Sloan JL, Yao L, Mannes AJ, Moshyedi A, Lee CR, Sciot R, De Smet L, Mautner V-F, Legius E. Diagnosis, management, and complications of glomus tumors of the fingers in neurofibromatosis type 1. Journal of Medical Genetics, 47 (8): 525-32. 2010. [PubMed]

Denayer E, Descheemaeker M-J, Stewart DR, Keymolen K, Coombes SL, Snow J, Thurm AE, Joseph LA, Fryns J-P, Legius E. Observations on Intelligence and Behavior in 15 Patients with Legius Syndrome. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 157(2): 123-8. 2011. [PubMed]

Soto E, Stewart DR, Mannes AJ, Ruppert SL, Baker K, Zlott D, Phillips J, Wroblewski GA, Handel D, Berger AM. Oral ketamine in a palliative care setting: A review of the literature and case report of a patient with NF1 and glomus tumor-associated CRPS. American Journal of Hospice and Palliative Medicine, 2011. [PubMed]

Stewart DR, Pemov A, Van Loo P, Beert E, Brems H, Sciot R, Claes K, Pak E, Dutra A, Lee CR and Legius E. Mitotic Recombination of Chromosome Arm 17q as a Cause of Loss of Heterozygosity of NF1 in Neurofibromatosis type 1-associated Glomus Tumors. Genes, Chromosomes and Cancer. [PubMed]

Last updated: February 24, 2016