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Samuel H. Cheshier, MD, PhD

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Languages Spoken: English

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.

Clinical Locations

Primary Children's Hospital
Pediatric Neurosurgery

801-662-5340

100 N Mario Capecchi Drive
Salt Lake City, UT  84113
Suite 3850

Specialties

  • Pediatric Neurosurgery

Board Certification and Academic Information

Academic Departments Neurosurgery - Associate Professor
Academic Divisions Pediatric Neurosurgery
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.

Academic Locations

Clinical Neurosciences Center

801-581-6908

175 North Medical Drive East
Department of Neurosurgery
Salt Lake City, UT  84132

Board Certification and Academic Information

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

Education History

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

Associates

Selected Publications - Journal Articles

Journal Article

  1. Morales E, Viskochil D, Hofmann J, Hagedorn C, Linscott L, Cheshier S, Bruggers CS (2021). Multiple Intraspinal Gangliogliomas in a Child With Neurofibromatosis Type 1: Case Report and Literature Review. (Epub ahead of print) J Pediatr Hematol Oncol.
  2. 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.
  3. 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, 1-8.
  4. 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.
  5. 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.
  6. Gardner M, Turner JE, Youssef OA, Cheshier S (2020). In Vitro Macrophage-Mediated Phagocytosis Assay of Brain Tumors. Cureus, 12(10), e10964.
  7. 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.
  8. 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 (Berl), 139(6), 1071-1088.
  9. 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.
  10. 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.
  11. 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.
  12. Cheshier S, Taylor MD, Ayrault O, Mueller S (2020). Introduction. Pediatric brain tumor. Neurosurg Focus, 48(1), E1.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.

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.

Patent

  1. 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.

Global Impact

Education History

Fellowship The Hospital for Sick Children
Paediatric Neurosurgery
Fellow
Research Fellow Lund University
Stem Cell Biology and Cell Therapy
Research Fellow

Huntsman Cancer Institute News

Talks with Docs: Samuel Cheshier, Pediatric Neurosurgeon

Fighting Brain Tumors in Kids

5 For The Fight Announces Inaugural Class of Cancer Research Fellows at Huntsman Cancer Institute

Committed to a Positive and Lasting Impact: The Engelstad Foundation

The Scope & Other Podcasts

  • Talks with Docs | Samuel Cheshier, MD
  • Update on Medulloblastoma Mestasis

Videos

Update on Medulloblastoma Mestasis

Talks with Docs | Samuel Cheshier, MD

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