
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 Neurosurgery801-662-5340
Specialties
Board Certification and Academic Information
Academic Departments | Neurosurgery
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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
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, 2010 |
Research Fellow | Lund University Stem Cell Biology and Cell Therapy Research Fellow, 2009 |
Residency | Stanford University School of Medicine Neurosurgery Resident, 2008 |
Postdoctoral Fellowship | Stanford University School of Medicine Neurosurgery and Pathology Postdoctoral Fellow, 2006 |
Doctoral Training | Stanford University School of Medicine Immunology Ph.D., 2005 |
Internship | Stanford University Hospitals and Clinics Surgery Intern, 2002 |
Professional Medical | Stanford University School of Medicine Medicine M.D., 2001 |
Undergraduate | University of California, Los Angeles Psychobiology B.S., 1993 |
Undergraduate | Loma Linda University Associates, 1991 |
Selected Publications - Journal Articles
Journal Article
- 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, 212137.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Gardner M, Turner JE, Youssef OA, Cheshier S (2020). In Vitro Macrophage-Mediated Phagocytosis Assay of Brain Tumors. Cureus, 12(10), e10964.
- 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.
- 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.
- 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.
- 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.
- 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.
- Cheshier S, Taylor MD, Ayrault O, Mueller S (2020). Introduction. Pediatric brain tumor. Neurosurg Focus, 48(1), E1.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
Other
Patent
- 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 |