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2015 Scientific Report

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Van Andel Research

Van Andel Research Institute | Scientific Report 2015 Matthew Steensma, M.D. Laboratory of Musculoskeletal Oncology Dr. Steensma received his B.A. from Hope College and his M.D. from Wayne State University School of Medicine in Detroit. He then completed research training in the laboratory of George Vande Woude (VARI) prior to a musculoskeletal oncology fellowship at Memorial Sloan-Kettering Cancer Center in New York. Upon completion of his surgical training, Dr. Steensma worked in the laboratory of Steve Goldring, studying mechanisms of pathologic bone resorption. There Dr. Steensma further developed his interest in the molecular and cellular mechanisms underlying bone and soft-tissue sarcomas. Dr. Steensma is a practicing surgeon in the Spectrum Health Medical Group, and he joined VARI as an Assistant Professor in 2010. From left: Schmidt, Lewis, Scholten, Smith, Steensma, Peacock, Kampfschulte, Pelle, Mooney, Foley. Staff Kevin Kampfschulte, B.A. Diana Lewis, A.S. Jacqueline Peacock, Ph.D. Students Marie Mooney, M.S. Akash PremKumar Courtney Schmidt D.J. Scholten, B.A. Mallory Smith Visiting Scientists Jessica Foley, M.D. Dominic Pelle, M.D. 30

Steensma Research Interests The Laboratory of Musculoskeletal Oncology conducts research which aims to develop new treatment strategies for sarcomas. Specifically, we are 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 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 of models of neurofibromatosis type 1 tumor progression; the identification of targetable patterns of intratumoral and intertumoral heterogeneity through next-generation sequencing; genotype-phenotype correlations in neurofibromatosis type 1 and related diseases; and mechanisms of chemotherapy resistance in bone and soft-tissue sarcomas. Recent Publications Pelle, Dominic W., Jonathan W. Ringler, Jacqueline D. Peacock, Kevin Kampfschulte, Donald J. Scholten II, Mary M. Davis, Deanna S. Mitchell, and Matthew R. Steensma. In press. Targeting receptor-activator nuclear kappa beta ligand in aneurysmal bone cysts: verification of target and therapeutic response. Translational Research. Puhaindran, M., S. Schlumbohm, K. Hamilton, M. Rich, D. Mitchell, and M.R. Steensma. In press. Radiation-induced osteosarcoma of the hand. Journal of Hand Surgery. Scholten, D.J., II, C.M. Timmer, J. Peacock, D.W. Pelle, B. Williams, and M.R. Steensma. In press. Hypoxia-mediated downregulation of Wnt/-catenin signaling is a viable target for chemoresistance in human osteosarcoma cells. PLoS One. Monks, Noel R., David M. Cherba, Steven G. Kamerling, Heather Simpson, Anthony W. Rusk, Derrick Carter, Emily Eugster, Marie Mooney, Robert Sigler, et al. 2013. A multi-site feasibility study for personalized medicine in canines with osteosarcoma. Journal of Translational Medicine 11: 158. Peacock, Jacqueline D., David Cherba, Kevin Kampfschulte, Mallory K. Smith, Noel R. Monks, Craig P. Webb, and Matthew R. Steensma. 2013. Molecular-guided therapy predictions reveal drug resistance phenotypes and treatment alternatives in malignant peripheral nerve sheath tumors. Journal of Translational Medicine 11: 213. Steensma, Matthew, and John H. Healey. 2013. Trends in the surgical treatment of pathologic proximal femur fractures among Musculoskeletal Tumor Society members. Clinical Orthopaedics and Related Research 471(6): 2000–2006. Steensma, Matthew R., Wakenda K. Tyler, Allison G. Shaber, Steven R. Goldring, F. Patrick Ross, Bart O. Williams, John H. Healey, and P. Edward Purdue. 2013. Targeting the giant cell tumor stromal cell: functional characterization and a novel therapeutic strategy. PLoS One 8(7): e69101. 31

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