Samuel H. Cheshier

Samuel H. Cheshier, MD, PhD

Languages spoken: English

Clinical Locations

Primary Children's Hospital

Pediatric Neurosurgery
801-662-5340

  • As a pediatric neurosurgeon, I witness first-hand the devastation that malignant brain tumors cause both the patients and families. The desire to help these people motivates me to conduct basic science research, with the goal of translating experiments into therapies. My laboratory has been utilizing a powerful immune-therapy strategy where CD47-SIRPa interactions between tumor cells and macrophages are blocked by Hu5F9-G4 in combination with potent immunotherapies including anti-cancer targeted monoclonal antibodies (anti-PDL1, anti-CD44, anti-Her2/Neu, anti-GD2), and modulators of macrophage activity (anti-CD40). My clinical practice specializing in brain tumor surgery has provided my laboratory with a large number of patient-derived malignant brain tumors from both pediatric and adult patients, which have already been used to conduct an excellent preclinical evaluation of Hu5F9-G4 against five pediatric malignant primary CNS tumors. While I was faculty at Stanford, I was in charge of the preclinical development of Hu5F9-G4 against malignant brain tumors, and I was a participant in the anti-CD47 Disease Team that helped develop the therapy into Phase 1 clinical trial. Since accepting my position at the Huntsman Cancer Institute, University of Utah School of Medicine as Director of Pediatric Surgical Neuro-Oncology, one of my laboratory’s main goals is to enhance anti-CD47 mediated phagocytosis by promoting the expression of pro-phagocytosis signals on brain cancer cells by irradiation. Irradiation is a well-known enhancer of pro-phagocytosis signal presentation on tumor cells. For example, calreticulin and phosphatidylserine are key pro-phagocytosis signals and are elevated in response to irradiation. I have developed preliminary data demonstrating anti-CD47 in combination with irradiation increased macrophage phagocytosis of human glioblastoma in vitro and increased survival in human glioblastoma-mouse orthotopic PDX models. Given the known efficacy of irradiation against malignant brain tumors, and the large medical infrastructure already present to deliver irradiation to patients, I feel my proposed studies to combine irradiation with anti-CD47, will provide significant data to justify clinical trials utilizing this combination. My current and previous research history have provided me a deep understanding (mechanism, efficacy, toxicity, combinatorial strategies) of anti-CD47 therapy in general. My laboratory can conduct the entire range of preclinical experiments testing anti-CD47 in vitro, as well as, in mouse models (human-mouse PDX, mouse models of primary brain tumors) to obtain data to justify and help design human trials in brain tumor patients. I believe anti-CD47 will be a foundational immune therapy that will be used as a key reagent in combination with other immune therapies and standard of care treatments.

    Specialties

    Board Certification

    American Board of Neurological Surgery (Neurosurg)
    American Board of Pediatric Neurological Surgery

  • As a pediatric neurosurgeon, I witness first-hand the devastation that malignant brain tumors cause both the patients and families. The desire to help these people motivates me to conduct basic science research, with the goal of translating experiments into therapies. My laboratory has been utilizing a powerful immune-therapy strategy where CD47-SIRPa interactions between tumor cells and macrophages are blocked by Hu5F9-G4 in combination with potent immunotherapies including anti-cancer targeted monoclonal antibodies (anti-PDL1, anti-CD44, anti-Her2/Neu, anti-GD2), and modulators of macrophage activity (anti-CD40). My clinical practice specializing in brain tumor surgery has provided my laboratory with a large number of patient-derived malignant brain tumors from both pediatric and adult patients, which have already been used to conduct an excellent preclinical evaluation of Hu5F9-G4 against five pediatric malignant primary CNS tumors. While I was faculty at Stanford, I was in charge of the preclinical development of Hu5F9-G4 against malignant brain tumors, and I was a participant in the anti-CD47 Disease Team that helped develop the therapy into Phase 1 clinical trial. Since accepting my position at the Huntsman Cancer Institute, University of Utah School of Medicine as Director of Pediatric Surgical Neuro-Oncology, one of my laboratory’s main goals is to enhance anti-CD47 mediated phagocytosis by promoting the expression of pro-phagocytosis signals on brain cancer cells by irradiation. Irradiation is a well-known enhancer of pro-phagocytosis signal presentation on tumor cells. For example, calreticulin and phosphatidylserine are key pro-phagocytosis signals and are elevated in response to irradiation. I have developed preliminary data demonstrating anti-CD47 in combination with irradiation increased macrophage phagocytosis of human glioblastoma in vitro and increased survival in human glioblastoma-mouse orthotopic PDX models. Given the known efficacy of irradiation against malignant brain tumors, and the large medical infrastructure already present to deliver irradiation to patients, I feel my proposed studies to combine irradiation with anti-CD47, will provide significant data to justify clinical trials utilizing this combination. My current and previous research history have provided me a deep understanding (mechanism, efficacy, toxicity, combinatorial strategies) of anti-CD47 therapy in general. My laboratory can conduct the entire range of preclinical experiments testing anti-CD47 in vitro, as well as, in mouse models (human-mouse PDX, mouse models of primary brain tumors) to obtain data to justify and help design human trials in brain tumor patients. I believe anti-CD47 will be a foundational immune therapy that will be used as a key reagent in combination with other immune therapies and standard of care treatments.

    Board Certification and Academic Information

    Academic Departments Neurosurgery -Primary
    Academic Divisions Pediatric Neurosurgery
    Board Certification
    American Board of Neurological Surgery (Neurosurg)
    American Board of Pediatric Neurological Surgery

    Education history

    Fellowship Paediatric Neurosurgery - The Hospital for Sick Children Fellow
    Stem Cell Biology and Cell Therapy - Lund University Research Fellow
    Postdoctoral Fellowship Neurosurgery and Pathology - Stanford University School of Medicine Postdoctoral Fellow
    Neurosurgery - Stanford University School of Medicine Resident
    Internship Surgery - Stanford University Hospitals and Clinics Intern
    Immunology - Stanford University School of Medicine Ph.D.
    Professional Medical Medicine - Stanford University School of Medicine M.D.
    Psychobiology - University of California, Los Angeles B.S.
    Undergraduate Loma Linda University Associates

    Selected Publications

    Journal Article

    1. Marquardt V, Theruvath J, Pauck D, Picard D, Qin N, Blmel L, Maue M, Bartl J, Ahmadov U, Langini M, Meyer FD, Cole A, Cruz-Cruz J, Graef CM, Wlfl M, Milde T, Witt O, Erdreich-Epstein A, Leprivier G, Kahlert U, Stefanski A, Sthler K, Keir ST, Bigner DD, Hauer J, Beez T, Knobbe-Thomsen CB, Fischer U, Felsberg J, Hansen FK, Vibhakar R, Venkatraman S, Cheshier SH, Reifenberger G, Borkhardt A, Kurz T, Remke M, Mitra S (2022). Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation. J Immunother Cancer, 11(1), e005871.
    2. Brockmeyer DL, Cheshier SH, Stevens J, Facelli JC, Rowe K, Heiss JD, Musolf A, Viskochil DH, Allen-Brady KL, Cannon-Albright LA (2022). A likely HOXC4 predisposition variant for Chiari malformations. J Neurosurg, 139(1), 266-274.
    3. Wu Z, Rajan S, Chung HJ, Raffeld M, Panneer Selvam P, Schweizer L, Perry A, Samuel D, Giannini C, Ragunathan A, Frosch MP, Marshall MS, Bou DR, Donev K, Neill SG, Fernandes I, Resnick A, Rood B, Cummings TJ, Buckley AF, Szymanski L, Neto OLA, Zach L, Colman H, Cheshier S, Ziskin J, Tyagi M, Capper D, Abdullaev Z, Cimino PJ, Quezado M, Pratt D, Aldape K (2022). Molecular and clinicopathologic characteristics of gliomas with EP300::BCOR fusions. Acta Neuropathol, 144(6), 1175-1178.
    4. Lucas CG, Davidson CJ, Alashari M, Putnam AR, Whipple NS, Bruggers CS, Mendez JS, Cheshier SH, Walker JB, Ramani B, Cadwell CR, Sullivan DV, Lu R, Mirchia K, Van Ziffle J, Devine P, Goldschmidt E, Hervey-Jumper SL, Gupta N, Oberheim Bush NA, Raleigh DR, Bollen A, Tihan T, Pekmezci M, Solomon DA, Phillips JJ, Perry A (2023). Targeted Next-Generation Sequencing Reveals Divergent Clonal Evolution in Components of Composite Pleomorphic Xanthoastrocytoma-Ganglioglioma. J Neuropathol Exp Neurol, 81(8), 650-657.
    5. Zhang M, Wong SW, Wright JN, Wagner MW, Toescu S, Han M, Tam LT, Zhou Q, Ahmadian SS, Shpanskaya K, Lummus S, Lai H, Eghbal A, Radmanesh A, Nemelka J, Harward S 2nd, Malinzak M, Laughlin S, Perreault S, Braun KRM, Lober RM, Cho YJ, Ertl-Wagner B, Ho CY, Mankad K, Vogel H, Cheshier SH, Jacques TS, Aquilina K, Fisher PG, Taylor M, Poussaint T, Vitanza NA, Grant GA, Pfister S, Thompson E, Jaju A, Ramaswamy V, Yeom KW (2022). MRI Radiogenomics of Pediatric Medulloblastoma: A Multicenter Study. Radiology, 304, 212137.
    6. Zhang M, Tam L, Wright J, Mohammadzadeh M, Han M, Chen E, Wagner M, Nemalka J, Lai H, Eghbal A, Ho CY, Lober RM, Cheshier SH, Vitanza NA, Grant GA, Prolo LM, Yeom KW, Jaju A (2022). Radiomics Can Distinguish Pediatric Supratentorial Embryonal Tumors, High-Grade Gliomas, and Ependymomas. AJNR Am J Neuroradiol, 43, 603-610.
    7. Baker C, Crevelt J, Whipple N, Bollo RJ, Cheshier S (2022). Treatment of a symptomatic thalamic pilocytic astrocytoma with reservoir placement and laser interstitial thermal therapy: illustrative case. J Neurosurg Case Lessons, 3(11).
    8. Lucas CG, Abdullaev Z, Bruggers CS, Mirchia K, Whipple NS, Alashari MM, Lowichik A, Cheshier S, Phillips JJ, Devine P, Solomon DA, Quezado M, Aldape KD, Perry A (2021). Activating NTRK2 and ALK receptor tyrosine kinase fusions extend the molecular spectrum of pleomorphic xanthoastrocytomas of early childhood: a diagnostic overlap with infant-type hemispheric glioma. Acta Neuropathol, 143(2), 283-286.
    9. Ojha R, Tantray I, Rimal S, Mitra S, Cheshier S, Lu B (2021). Regulation of reverse electron transfer at mitochondrial complex I by unconventional Notch action in cancer stem cells. Dev Cell, 57(2), 260-276.e9.
    10. Zhang M, Wang E, Yecies D, Tam LT, Han M, Toescu S, Wright JN, Altinmakas E, Chen E, Radmanesh A, Nemelka J, Oztekin O, Wagner MW, Lober RM, Ertl-Wagner B, Ho CY, Mankad K, Vitanza NA, Cheshier SH, Jacques TS, Fisher PG, Aquilina K, Said M, Jaju A, Pfister S, Taylor MD, Grant GA, Mattonen S, Ramaswamy V, Yeom KW (2021). Radiomic Signatures of Posterior Fossa Ependymoma: Molecular Subgroups and Risk Profiles. Neuro Oncol, 24, 986-994.
    11. Thomsen W, Maese L, Vagher J, Moore K, Cheshier SH, Hofmann JW, Bruggers C (2022). Early Presentation of Homozygous Mismatch Repair Deficient Glioblastoma in Teen With Lynch Syndrome: Implications for Treatment and Surveillance. JCO Precis Oncol, 5, 670-675.
    12. Zhang M, Wong SW, Wright JN, Toescu S, Mohammadzadeh M, Han M, Lummus S, Wagner MW, Yecies D, Lai H, Eghbal A, Radmanesh A, Nemelka J, Harward S, Malinzak M, Laughlin S, Perreault S, Braun KRM, Vossough A, Poussaint T, Goetti R, Ertl-Wagner B, Ho CY, Oztekin O, Ramaswamy V, Mankad K, Vitanza NA, Cheshier SH, Said M, Aquilina K, Thompson E, Jaju A, Grant GA, Lober RM, Yeom KW (2021). Machine Assist for Pediatric Posterior Fossa Tumor Diagnosis: A Multinational Study. Neurosurgery, 89(5), 892-900.
    13. Morales E, Viskochil D, Hofmann J, Hagedorn C, Linscott L, Cheshier S, Bruggers CS (2020). Multiple Intraspinal Gangliogliomas in a Child With Neurofibromatosis Type 1: Case Report and Literature Review. J Pediatr Hematol Oncol, 43(7), e979-e982.
    14. Hamrick FA, Karsy M, Bruggers CS, Putnam AR, Hedlund GL, Cheshier SH (2021). Developmentally anomalous cerebellar encephalocele arising within the cerebellopontine angle and extending into the adjacent skull base in a pediatric patient. Childs Nerv Syst, 37(9), 2943-2947.
    15. Zhang M, Wong SW, Lummus S, Han M, Radmanesh A, Ahmadian SS, Prolo LM, Lai H, Eghbal A, Oztekin O, Cheshier SH, Fisher PG, Ho CY, Vogel H, Vitanza NA, Lober RM, Grant GA, Jaju A, Yeom KW (2021). Radiomic Phenotypes Distinguish Atypical Teratoid/Rhabdoid Tumors from Medulloblastoma. AJNR Am J Neuroradiol, 42(9), 1702-1708.
    16. Tam LT, Yeom KW, Wright JN, Jaju A, Radmanesh A, Han M, Toescu S, Maleki M, Chen E, Campion A, Lai HA, Eghbal AA, Oztekin O, Mankad K, Hargrave D, Jacques TS, Goetti R, Lober RM, Cheshier SH, Napel S, Said M, Aquilina K, Ho CY, Monje M, Vitanza NA, Mattonen SA (2021). MRI-based radiomics for prognosis of pediatric diffuse intrinsic pontine glioma: an international study. Neurooncol Adv, 3(1), vdab042.
    17. Higgins DMO, Caliva M, Schroeder M, Carlson B, Upadhyayula PS, Milligan BD, Cheshier SH, Weissman IL, Sarkaria JN, Meyer FB, Henley JR (2020). Semaphorin 3A mediated brain tumor stem cell proliferation and invasion in EGFRviii mutant gliomas. BMC Cancer, 20(1), 1213.
    18. Quon JL, Han M, Kim LH, Koran ME, Chen LC, Lee EH, Wright J, Ramaswamy V, Lober RM, Taylor MD, Grant GA, Cheshier SH, Kestle JRW, Edwards MSB, Yeom KW (2020). Artificial intelligence for automatic cerebral ventricle segmentation and volume calculation: a clinical tool for the evaluation of pediatric hydrocephalus. J Neurosurg Pediatr, 27, 1-8.
    19. Iv M, Ng NN, Nair S, Zhang Y, Lavezo J, Cheshier SH, Holdsworth SJ, Moseley ME, Rosenberg J, Grant GA, Yeom KW (2020). Brain Iron Assessment after Ferumoxytol-enhanced MRI in Children and Young Adults with Arteriovenous Malformations: A Case-Control Study. Radiology, 297(2), 438-446.
    20. Quon JL, Chen LC, Kim L, Grant GA, Edwards MSB, Cheshier SH, Yeom KW (2020). Deep Learning for Automated Delineation of Pediatric Cerebral Arteries on Pre-operative Brain Magnetic Resonance Imaging. Front Surg, 7, 517375.
    21. Gardner M, Turner JE, Youssef OA, Cheshier S (2020). In Vitro Macrophage-Mediated Phagocytosis Assay of Brain Tumors. Cureus, 12(10), e10964.
    22. Quon JL, Bala W, Chen LC, Wright J, Kim LH, Han M, Shpanskaya K, Lee EH, Tong E, Iv M, Seekins J, Lungren MP, Braun KRM, Poussaint TY, Laughlin S, Taylor MD, Lober RM, Vogel H, Fisher PG, Grant GA, Ramaswamy V, Vitanza NA, Ho CY, Edwards MSB, Cheshier SH, Yeom KW (2020). Deep Learning for Pediatric Posterior Fossa Tumor Detection and Classification: A Multi-Institutional Study. AJNR Am J Neuroradiol, 41(9), 1718-1725.
    23. Mondal G, Lee JC, Ravindranathan A, Villanueva-Meyer JE, Tran QT, Allen SJ, Barreto J, Gupta R, Doo P, Van Ziffle J, Onodera C, Devine P, Grenert JP, Samuel D, Li R, Metrock LK, Jin LW, Antony R, Alashari M, Cheshier S, Whipple NS, Bruggers C, Raffel C, Gupta N, Kline CN, Reddy A, Banerjee A, Hall MD, Mehta MP, Khatib Z, Maher OM, Brathwaite C, Pekmezci M, Phillips JJ, Bollen AW, Tihan T, Lucas JT Jr, Broniscer A, Berger MS, Perry A, Orr BA, Solomon DA (2020). Pediatric bithalamic gliomas have a distinct epigenetic signature and frequent EGFR exon 20 insertions resulting in potential sensitivity to targeted kinase inhibition. Acta Neuropathol, 139(6), 1071-1088.
    24. Lucas CG, Villanueva-Meyer JE, Whipple N, Oberheim Bush NA, Cooney T, Chang S, McDermott M, Berger M, Cham E, Sun PP, Putnam A, Zhou H, Bollo R, Cheshier S, Poppe MM, Fung KM, Sung S, Glenn C, Fan X, Bannykh S, Hu J, Danielpour M, Li R, Alva E, Johnston J, Van Ziffle J, Onodera C, Devine P, Grenert JP, Lee JC, Pekmezci M, Tihan T, Bollen AW, Perry A, Solomon DA (2019). Myxoid glioneuronal tumor, PDGFRA p.K385-mutant: clinical, radiologic, and histopathologic features. Brain Pathol, 30(3), 479-494.
    25. Theruvath J, Sotillo E, Mount CW, Graef CM, Delaidelli A, Heitzeneder S, Labanieh L, Dhingra S, Leruste A, Majzner RG, Xu P, Mueller S, Yecies DW, Finetti MA, Williamson D, Johann PD, Kool M, Pfister S, Hasselblatt M, Frhwald MC, Delattre O, Surdez D, Bourdeaut F, Puget S, Zaidi S, Mitra SS, Cheshier S, Sorensen PH, Monje M, Mackall CL (2020). Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. Nat Med, 26(5), 712-719.
    26. Gholamin S, Youssef OA, Rafat M, Esparza R, Kahn S, Shahin M, Giaccia AJ, Graves EE, Weissman I, Mitra S, Cheshier SH (2019). Irradiation or temozolomide chemotherapy enhances anti-CD47 treatment of glioblastoma. Innate Immun, 26(2), 130-137.
    27. Cheshier S, Taylor MD, Ayrault O, Mueller S (2020). Introduction. Pediatric brain tumor. Neurosurg Focus, 48(1), E1.
    28. Cole AP, Hoffmeyer E, Chetty SL, Cruz-Cruz J, Hamrick F, Youssef O, Cheshier S, Mitra SS (2020). Microglia in the Brain Tumor Microenvironment. Adv Exp Med Biol, 1273, 197-208.
    29. Shpanskaya K, Quon JL, Lober RM, Nair S, Johnson E, Cheshier SH, Edwards MSB, Grant GA, Yeom KW (2019). Diffusion tensor magnetic resonance imaging of the optic nerves in pediatric hydrocephalus. Neurosurg Focus, 47(6), E16.
    30. Mohole J, Ho AL, Cannon JGD, Pendharkar AV, Sussman ES, Hong DS, Cheshier SH, Grant GA (2019). Topical Vancomycin for Surgical Prophylaxis in Pediatric Craniofacial Surgeries. J Craniofac Surg, 30(7), 2163-2167.
    31. Yecies D, Shpanskaya K, Jabarkheel R, Maleki M, Bruckert L, Cheshier SH, Hong D, Edwards MSB, Grant GA, Yeom KW (2019). Arterial spin labeling perfusion changes of the frontal lobes in children with posterior fossa syndrome. J Neurosurg Pediatr, 1-7.
    32. SoRelle ED, Yecies DW, Liba O, Bennett FC, Graef CM, Dutta R, Mitra S, Joubert LM, Cheshier S, Grant GA, de la Zerda A (2019). Spatiotemporal Tracking of Brain-Tumor-Associated Myeloid Cells in Vivo through Optical Coherence Tomography with Plasmonic Labeling and Speckle Modulation. ACS Nano, 13(7), 7985-7995.
    33. Huang Y, Singer TG, Iv M, Lanzman B, Nair S, Stadler JA, Wang J, Edwards MSB, Grant GA, Cheshier SH, Yeom KW (2019). Ferumoxytol-enhanced MRI for surveillance of pediatric cerebral arteriovenous malformations. J Neurosurg Pediatr, 1-8.
    34. Quon JL, Kim LH, Hwang PH, Patel ZM, Grant GA, Cheshier SH, Edwards MSB (2019). Transnasal endoscopic approach for pediatric skull base lesions: a case series. J Neurosurg Pediatr, 1-12.

    Review

    1. Giberson CE, Cheshier SH, Poree LR, Saulino MF (2023). Diaphragm Pacing: A Safety, Appropriateness, Financial Neutrality, and Efficacy Analysis of Treating Chronic Respiratory Insufficiency. [Review]. Neuromodulation, 26(3), 490-497.

    Book Chapter

    1. Cheshier SH, Doz F, Ellison D, Merchant TE and Pfister SM (2023). Embryonal tumours. In Tracy Batchelor, Ryo Nishikawa, Nancy Tarbell, Michael Weller (Eds.), Oxford Textbook of Neuro-Oncology (2nd). Oxford University Press.

    Case Report

    1. Pan J, Ho AL, Pendharkar AV, Sussman ES, Casazza M, Cheshier SH, Grant GA (2019). Brain abscess caused by Trueperella bernardiae in a child. Surg Neurol Int, 10, 35.

    Editorial

    1. Bruggers CS, Linscott L, Lee JC, Perry A, Klonoski J, Viskochil D, Cheshier S, Afify Z (2022). Molecular characterization of metachronous atypical teratoid rhabdoid tumors occurring in a young man 15 years apart. Pediatr Blood Cancer, 70, e29836.

    Other

    1. Hamrick FA, Karsy M, Bruggers CS, Putnam AR, Hedlund GL, Cheshier SH (2021). Correction to: Developmentally anomalous cerebellar encephalocele arising within the cerebellopontine angle and extending into the adjacent skull base in a pediatric patient. Childs Nerv Syst (37(12), p. 3977). Germany.

    Patent

    1. Sharareh Gholamin, Samuel Cheshier Siddhartha S. Mitra , Irving L. Weissman (2018). Treatment of Pediatric Brain Tumors with Targeting of CD47 Pathway. U.S. Patent No. United States Patent No. 11,078,272. Washington, D.C.:U.S. Patent and Trademark Office.
    2. Kalani Y, Cheshier SH, Nusse R (2006). Wnts as Therapeutic Tools for Neural Regeneration. U.S. Patent No. 12041538. Washington, D.C.:U.S. Patent and Trademark Office.