Steensma
Laboratory

Translational NF1 Oncology

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.

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122 peer-reviewed papers published in 2024, 63 of which were in high-impact journals
15 VAI-SU2C Epigenetics Dream Team clinical trials launched to date
10 clinical trials co-funded by VAI & Cure Parkinson's (out of 41 total International Linked Clinical Trials Program trials)

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Matt Steensma, M.D.

Associate Professor, Department of Cell Biology

Areas of Expertise

Sarcomas, neurofibromatosis type 1, models of NF1 tumor progression, translational therapies

Biography

Dr. Steensma received his B.A. from Hope College in Holland, Mich., and his M.D. from Wayne State University School of Medicine in Detroit, Mich. He subsequently completed internship and residency training in the Grand Rapids Orthopaedic Surgery Residency Program. After completing residency, he trained in the laboratories of Drs. George Vande Woude and Rick Hay at VAI under an Orthopaedic Research and Education Foundation training award. Subsequently, Dr. Steensma was admitted into the prestigious fellowship program in Musculoskeletal Surgical Oncology in the Department of Surgery at Memorial Sloan Kettering Cancer Center in New York where he obtained sub-specialty training in the surgical management of musculoskeletal tumors. His fellowship in New York also provided Dr. Steensma with the opportunity to work in the laboratory of Dr. Steve Goldring, Chief Scientific Officer of the Hospital for Special Surgery (HSS) in New York. Dr. Goldring is one of the world’s leading orthopaedic researchers and has a particularly strong reputation for training leading clinician-scientists. During his training with Dr. Goldring, Dr. Steensma further developed his interests in understanding the molecular and cellular mechanisms underlying the development of bone and soft-tissue sarcomas. Dr. Steensma joined Van Andel Institute in 2010 as an Associate Scientific Investigator in the Center for Skeletal Disease Research. In 2014, he was named as one of the winners of the inaugural Francis S. Collins Scholars Program in Neurofibromatosis Clinical and Translational Research.

SELECTED PUBLICATIONS

Arumugam M, Tovar EA, Essenburg CJ, Dischinger PS, Beddows I, Wolfrum E, Madaj ZB, Turner L, Feenstra K, Gallik KL, Cohen L, Nichols M, Sheridan RTC, Esquibel CR, Mouneimne G, Graveel CR, Steensma MR. 2024. Nf1 deficiency modulates stromal environment in the pretumorigenic rat mammary gland. Front Cell Dev Biol 12.

Grit JL, Turner L, Essenburg CJ, Gallik KL, Dischinger PS, Shurlow ND, Pate MJ, Graveel CR, Steensma MR. 2024. Ex-vivopatient-derived explant model for neurofibromatosis type 1-related cutaneous neurofibromas. J Invest Dermatol 21:S0022-202X(24)00117-9.

House RJ, Tovar EA, Redlon LN, Essenburg CJ, Dischinger PS, Ellis AE, Beddows I, Sheldon RD, Lien EC, Graveel CR, Steensma MR. 2024. NF1 deficiency drives metabolic reprogramming in ER+ breast cancer. Mol Metab 80:101876.

Grit JL, Johnson BK, Dischinger PS, Essenburg CJ, Adams M, Campbell S, Pollard K, Pratilas CA, Triche TJ Jr., Graveel CR, Steensma MR. 2021. Distinctive epigenomic alterations in NF1-deficient cutaneous and plexiform neurofibromas drive differential MKK/p38 signaling. Epi Chromatin 14(7).

Tovar EA, Sheridan R, Essenburg CJ, Dischinger PS, Arumugam M, Callaghan ME, Graveel CR*, Steensma MR*. 2020. Dissecting the rat mammary gland: Isolation, characterization and culture of purified mammary epithelial cells and fibroblasts. Bio-protocol 10(22).
*Equal contributions

Grit JL, Pridgeon MG, Essenburg CJ, Wolfrum E, Madaj ZB, Turner L, Wulfkuhle J, Petricoin EF 3rd, Graveel CR, Steensma MR. 2020. Kinome profiling of NF1-related MPNSTs in response to kinase inhibition and doxorubicin reveals therapeutic vulnerabilities. Genes (Basel) 11(3):331

Dischinger PS, Tovar EA, Essenburg CJ, Madaj ZB, Gardner EE, Callaghan ME, Turner AN, Challa AK, Kempston T, Eagleson B, Kesterson RA, Bronson RT, Bowman MJ, Graveel CR, Steensma MR. 2018. NF1 deficiency correlates with estrogen receptor signaling and diminished survival in breast cancer. npj Breast Cancer 4.

Peacock JD, Pridgeon MG, Tovar EA, Essenburg CJ, Bowman M, Madaj Z, Koeman J, Boguslawski EA, Grit J, Dodd RD, Khachaturov V, Cardona DM, Chen M, Kirsch DG, Maina F, Dono R, Winn ME, Graveel CR, Steensma MR. 2018. Genomic status of MET potentiates sensitivity to MET and MEK inhibition in NF1-related malignant peripheral nerve sheath tumors. Cancer Res 78(13):3672–3687.

Pridgeon MG, Grohar PJ, Steensma MR, Williams BO. 2017. Wnt signaling in Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors. Curr Osteo Rep 15(4):239–246.

Linklater ES, Tovar EA, Essenburg CJ, Turner L, Madaj Z, Winn ME, Melnik MK, Korkaya H, Maroun CR, Christensen JG, Steensma MR, Boerner JL, Graveel CR. 2016. Targeting MET and EGFR crosstalk signaling in triple-negative breast cancers. Oncotarget 7(43):69903.

Steensma MR, Jebson P. 2016. Primary bone sarcomas of the upper extremity. In Tumors of the Hand and Upper Extremity. Edward A. Athanasian, Peter J. Jebson, Sanjeev Kakar, Peter M. Murray, eds. Chicago, IL: American Society for Surgery of the Hand, p. 6.

Lane BR, Bissonnette J, Waldherr T, Ritz-Holland D, Chesla D, Cottingham SL, Alberta S, Liu C, Thompson AB, Graveel C, MacKeigan JP, Noyes SL, Smith J, Lakhani N, Steensma MR. 2015. Development of a Center for Personalized Cancer Care at a regional cancer center: Feasibility trial of an institutional tumor sequencing advisory board. J Mol Diagn 17(6):695–704.

Foley JM, Scholten DJ 2nd, Monks N, Cherba D, Monsma D, Davidson P, Dylewski D, Dykema K, Winn M, Steensma MR. 2015. Anoikis-resistant subpopulations of human osteosarcoma display significant chemoresistance and are sensitive to targeted epigenetic therapies predicted by expression profiling. J Trans Med 3:110.

Peacock JD, Dykema KJ, Toriello HV, Mooney MR, Scholten DJ 2nd, Winn ME, Borgman A, Duesbery NS, Hiemenga JA, Liu C, Campbell S, Nickoloff BP, Williams BO, Steensma MR. 2015. Oculoectodermal syndrome is a mosaic RASopathy associated with KRAS alterations. Am J Med Genet 167(7):1429–1435.

Pelle DW, Ringler JW, Peacock JD, Kampfschulte K, Scholten DJ 2nd, Davis MD, Mitchell DS, Steensma MR. 2014. Targeting receptor-activator nuclear kappa beta ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res 164(2):139–148.

Pelle DW, Peacock JD, Schmidt CL, Kampfschulte K, Scholten DJ 2nd, Russo SS, Easton KJ, Steensma MR. 2014. Genetic and functional studies of the intervertebral disc: A novel murine intervertebral disc model. PLoS One 9(12)e112454.

Scholten DJ 2nd, Timmer CM, Peacock JD, Pelle DW, Williams BO, Steensma MR. 2014. Down regulation of Wnt signaling mitigates hypoxia-induced chemoresistance in human osteosarcoma cells. PLoS One 9(10):e111431.

Puhaindran M, Schlumbohm S, Hamilton K, Rich M, Mitchell D, Steensma MR. 2014. Radiation-induced osteosarcoma of the hand. J Hand Surg Am 39(6):1151–1154.

Pelle DW, Ringler JW, Peacock JD, Kampfschulte K, Scholten II DJ, Davis MD, Mitchell DS, Steensma MR. 2014. Targeting receptor-activator nuclear kappa beta ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res 164(2):139–148.

Peacock JD, Cherba D, Kampfschulte K, Smith MK, Monks NR, Webb CP, Steensma MR. 2013. Molecular-guided therapy predictions reveal drug resistance phenotypes and treatment alternatives in malignant peripheral nerve sheath tumors. J Transl Med 11(1):213.

Steensma MR, Tyler WK, Shaber AG, Goldring SR, Ross FP, Williams BO, Healey JH, Purdue PE. 2013. Targeting the giant cell tumor stromal cell: functional characterization and a novel therapeutic strategy. PLoS One 8(7): e69101.

Monks NR, Cherba DM, Kamerling SG, Simpson H, Rusk AW, Carter D, Eugster E, Mooney M, Sigler R, Steensma MR, Grabinski T, Marotti KR, Webb CP. 2013. A multi-site feasibility study for personalized medicine in canines with osteosarcoma. J Transl Med 11:158.

Valkenburg KC, Steensma MR, Williams BO, Zhong Z. 2013. Skeletal metastasis: treatments, mouse models, and the Wnt signaling. Chin J Cancer 32(7):380–396.

Steensma MR, Healey JH. 2013. Trends in the surgical treatment of pathologic proximal femur fractures among Musculoskeletal Tumor Society members. Clin Orthop and Relat Res 471(6): 2000–2006.

Steensma MR, Morris C. 2013. Ewing’s sarcoma. In Orthopaedic Knowledge Update: Musculoskeletal Tumors 3, J. Sybil Biermann, ed. Rosemont, IL: American Academy of Orthopaedic Surgeons.

Steensma MR, Boland PJ, Morris CD, Athanasian E, Healey JH. 2012. Endoprosthetic treatment is more durable for pathologic proximal femur fractures. Clin Orthop Relat Res 470(3):920–926.

Zhong Z, Williams BO, Steensma MR. 2012. Commentary on “The activation of Beta-catenin by Gs contributes to the etiology of phenotypes seen in fibrous dysplasia and McCune–Albright syndrome”. IBMS BoneKEy 9.

Puhaindran M, Farooki A, Steensma MR, Hameed M, Healey JH, Boland PJ. 2011. Atypical subtrochanteric femoral fractures in patients with skeletal malignant involvement treated with intravenous bisphosphonates. J Bone Joint Surg Am 93(13):1235–1242.

Puhaindran M, Steensma MR, Athanasian E. 2010. Partial hand preservation for large soft tissue sarcomas of the hand. J Hand Surg Am 35(2):291–295.

Steensma MR, Jabara M, Anderson JG, Bohay DR. 2006. Flexor hallucis longus tendon transfer for hallux claw toe deformity and vertical instability of the metatarsophalangeal joint. Foot Ankle Int 27(9):689–692.

Steensma MR, Anderson JG, Bohay DR. 2005. Update on diseases and treatment of the peroneal tendon including peroneal tendon tear, subluxating peroneal tendon, and tendinosis. Curr Opin Ortho 2:60–65.