Eric Thompson

Overview:

My translational and clinical research focus is pediatric brain tumors. My lab investigates 1) the mechanism of oncolytic viral immunotherapy for the treatment of solid tumor and disseminated medulloblastoma, and 2) the role of Abelson family kinases (ABL1 and ABL2) in the promotion of leptomeningeal dissemination of pediatric brain tumors.

My clinical research focuses on 1) using a novel peptide vaccine to target CMV antigens to treat children with recurrent medulloblastoma and malignant glioma and 2) using oncolytic poliovirus to treat children with recurrent malignant glioma.

Positions:

Associate Professor of Neurosurgery

Neurosurgery
School of Medicine

Associate Professor in Pathology

Pathology
School of Medicine

Associate Professor in Pediatrics

Pediatrics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 2002

Duke University

M.D. 2006

University of Nebraska, College of Medicine

Neurological Surgery Resident, Neurosurgery

Oregon Health and Science University

Pediatric Neurological Surgery Fellow, Neurosurgery

The Hospital For Sick Children

Grants:

The Role of CD155 in Leptomeningeal Dissemination and Oncolytic Virus Susceptibility in the Medulloblastoma Microenvironment

Administered By
Neurosurgery
Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Phase-1 clinical trial of PVSRIPO oncolytic immunotherapy in pediatric HGG

Administered By
Neurosurgery
Awarded By
Solving Kids' Cancer
Role
Co Investigator
Start Date
End Date

Phase Ib study of Oncolytic Polio/Rhinovirus Recombinant Against Recurrent Malignant Glioma in Children

Administered By
Duke Cancer Institute
Awarded By
Istari Oncology
Role
Principal Investigator
Start Date
End Date

ABL Kinases as Drivers of Medulloblastoma Leptomeningeal Dissemination

Administered By
Neurosurgery
Awarded By
American Society of Pediatric Nephrology
Role
Principal Investigator
Start Date
End Date

Oncolytic Poliovirus Immunotherapy for Pediatric Medulloblastoma

Administered By
Neurosurgery
Awarded By
Musella Foundation For Brain Tumor Research & Information, Inc
Role
Principal Investigator
Start Date
End Date

Publications:

Author Correction: Failure of human rhombic lip differentiation underlies medulloblastoma formation.

Authors
Hendrikse, LD; Haldipur, P; Saulnier, O; Millman, J; Sjoboen, AH; Erickson, AW; Ong, W; Gordon, V; Coudière-Morrison, L; Mercier, AL; Shokouhian, M; Suárez, RA; Ly, M; Borlase, S; Scott, DS; Vladoiu, MC; Farooq, H; Sirbu, O; Nakashima, T; Nambu, S; Funakoshi, Y; Bahcheli, A; Diaz-Mejia, JJ; Golser, J; Bach, K; Phuong-Bao, T; Skowron, P; Wang, EY; Kumar, SA; Balin, P; Visvanathan, A; Lee, JJY; Ayoub, R; Chen, X; Chen, X; Mungall, KL; Luu, B; Bérubé, P; Wang, YC; Pfister, SM; Kim, S-K; Delattre, O; Bourdeaut, F; Doz, F; Masliah-Planchon, J; Grajkowska, WA; Loukides, J; Dirks, P; Fèvre-Montange, M; Jouvet, A; French, PJ; Kros, JM; Zitterbart, K; Bailey, SD; Eberhart, CG; Rao, AAN; Giannini, C; Olson, JM; Garami, M; Hauser, P; Phillips, JJ; Ra, YS; de Torres, C; Mora, J; Li, KKW; Ng, H-K; Poon, WS; Pollack, IF; López-Aguilar, E; Gillespie, GY; Van Meter, TE; Shofuda, T; Vibhakar, R; Thompson, RC; Cooper, MK; Rubin, JB; Kumabe, T; Jung, S; Lach, B; Iolascon, A; Ferrucci, V; de Antonellis, P; Zollo, M; Cinalli, G; Robinson, S; Stearns, DS; Van Meir, EG; Porrati, P; Finocchiaro, G; Massimino, M; Carlotti, CG; Faria, CC; Roussel, MF; Boop, F; Chan, JA; Aldinger, KA; Razavi, F; Silvestri, E; McLendon, RE; Thompson, EM; Ansari, M; Garre, ML; Chico, F; Eguía, P; Pérezpeña, M; Morrissy, AS; Cavalli, FMG; Wu, X; Daniels, C; Rich, JN; Jones, SJM; Moore, RA; Marra, MA; Huang, X; Reimand, J; Sorensen, PH; Wechsler-Reya, RJ; Weiss, WA; Pugh, TJ; Garzia, L; Kleinman, CL; Stein, LD; Jabado, N; Malkin, D; Ayrault, O; Golden, JA; Ellison, DW; Doble, B; Ramaswamy, V; Werbowetski-Ogilvie, TE; Suzuki, H; Millen, KJ; Taylor, MD
MLA Citation
Hendrikse, Liam D., et al. “Author Correction: Failure of human rhombic lip differentiation underlies medulloblastoma formation.Nature, vol. 612, no. 7940, Dec. 2022, p. E12. Pubmed, doi:10.1038/s41586-022-05578-0.
URI
https://scholars.duke.edu/individual/pub1557713
PMID
36446943
Source
pubmed
Published In
Nature
Volume
612
Published Date
Start Page
E12
DOI
10.1038/s41586-022-05578-0

CD155 is a putative therapeutic target in medulloblastoma.

BACKGROUND: Medulloblastoma is the most common pediatric malignant brain tumor, consisting of four molecular subgroups (WNT, SHH, Group 3, Group 4) and 12 subtypes. Expression of the cell surface poliovirus receptor (PVR), CD155, is necessary for entry of the viral immunotherapeutic agent, PVSRIPO, a polio:rhinovirus chimera. CD155, physiologically expressed in the mononuclear phagocytic system, is widely expressed ectopically in solid tumors. The objective of this study is to elucidate CD155 expression as both a receptor for PVSRIPO and a therapeutic target in medulloblastoma. METHODS: PVR mRNA expression was determined in several patient cohorts and human medulloblastoma cell lines. Patient samples were also analyzed for CD155 expression using immunohistochemistry and cell lines were analyzed using Western Blots. CD155 was blocked using a monoclonal antibody and cell viability, invasion, and migration were assessed. RESULTS AND DISCUSSION: PVR mRNA expression was highest in the WNT subgroup and lowest in Group 4. PVR expression in the subgroups of medulloblastoma were similar to other pediatric brain and non-brain tumors. PVR expression was largely not associated with subgroup or subtype. Neither PVR protein expression intensity nor frequency were associated with overall survival. PVR expression was elevated in Group 3 patients with metastases but there was no difference in paired primary and metastatic medulloblastoma. Blocking PVR resulted in dose-dependent cell death, decreased invasion in vitro, and modestly inhibited cell migration. CONCLUSIONS: CD155 is expressed across medulloblastoma subgroups and subtypes. Blocking CD155 results in cell death and decreased cellular invasion. This study provides rationale for CD155-targeting agents including PVSRIPO and antibody-mediated blockade of CD155.
Authors
Li, S; McLendon, R; Sankey, E; Kornahrens, R; Lyne, A-M; Cavalli, FMG; McKay, Z; Herndon, JE; Remke, M; Picard, D; Gromeier, M; Brown, M; Thompson, EM
MLA Citation
Li, Sean, et al. “CD155 is a putative therapeutic target in medulloblastoma.Clin Transl Oncol, Oct. 2022. Pubmed, doi:10.1007/s12094-022-02975-9.
URI
https://scholars.duke.edu/individual/pub1555228
PMID
36301489
Source
pubmed
Published In
Clin Transl Oncol
Published Date
DOI
10.1007/s12094-022-02975-9

Failure of human rhombic lip differentiation underlies medulloblastoma formation.

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain1-4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage5-8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES+KI67+ unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB.
Authors
Hendrikse, LD; Haldipur, P; Saulnier, O; Millman, J; Sjoboen, AH; Erickson, AW; Ong, W; Gordon, V; Coudière-Morrison, L; Mercier, AL; Shokouhian, M; Suárez, RA; Ly, M; Borlase, S; Scott, DS; Vladoiu, MC; Farooq, H; Sirbu, O; Nakashima, T; Nambu, S; Funakoshi, Y; Bahcheli, A; Diaz-Mejia, JJ; Golser, J; Bach, K; Phuong-Bao, T; Skowron, P; Wang, EY; Kumar, SA; Balin, P; Visvanathan, A; Lee, JJY; Ayoub, R; Chen, X; Chen, X; Mungall, KL; Luu, B; Bérubé, P; Wang, YC; Pfister, SM; Kim, S-K; Delattre, O; Bourdeaut, F; Doz, F; Masliah-Planchon, J; Grajkowska, WA; Loukides, J; Dirks, P; Fèvre-Montange, M; Jouvet, A; French, PJ; Kros, JM; Zitterbart, K; Bailey, SD; Eberhart, CG; Rao, AAN; Giannini, C; Olson, JM; Garami, M; Hauser, P; Phillips, JJ; Ra, YS; de Torres, C; Mora, J; Li, KKW; Ng, H-K; Poon, WS; Pollack, IF; López-Aguilar, E; Gillespie, GY; Van Meter, TE; Shofuda, T; Vibhakar, R; Thompson, RC; Cooper, MK; Rubin, JB; Kumabe, T; Jung, S; Lach, B; Iolascon, A; Ferrucci, V; de Antonellis, P; Zollo, M; Cinalli, G; Robinson, S; Stearns, DS; Van Meir, EG; Porrati, P; Finocchiaro, G; Massimino, M; Carlotti, CG; Faria, CC; Roussel, MF; Boop, F; Chan, JA; Aldinger, KA; Razavi, F; Silvestri, E; McLendon, RE; Thompson, EM; Ansari, M; Garre, ML; Chico, F; Eguía, P; Pérezpeña, M; Morrissy, AS; Cavalli, FMG; Wu, X; Daniels, C; Rich, JN; Jones, SJM; Moore, RA; Marra, MA; Huang, X; Reimand, J; Sorensen, PH; Wechsler-Reya, RJ; Weiss, WA; Pugh, TJ; Garzia, L; Kleinman, CL; Stein, LD; Jabado, N; Malkin, D; Ayrault, O; Golden, JA; Ellison, DW; Doble, B; Ramaswamy, V; Werbowetski-Ogilvie, TE; Suzuki, H; Millen, KJ; Taylor, MD
MLA Citation
Hendrikse, Liam D., et al. “Failure of human rhombic lip differentiation underlies medulloblastoma formation.Nature, vol. 609, no. 7929, Sept. 2022, pp. 1021–28. Pubmed, doi:10.1038/s41586-022-05215-w.
URI
https://scholars.duke.edu/individual/pub1550866
PMID
36131014
Source
pubmed
Published In
Nature
Volume
609
Published Date
Start Page
1021
End Page
1028
DOI
10.1038/s41586-022-05215-w

MRI Radiogenomics of Pediatric Medulloblastoma: A Multicenter Study.

Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection of patient groups suitable for targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant MB molecular subgroups. Materials and Methods In this retrospective study, consecutive pediatric patients with newly diagnosed MB at MRI at 12 international pediatric sites between July 1997 and May 2020 were identified. There were 1800 features extracted from T2- and contrast-enhanced T1-weighted preoperative MRI scans. A two-stage sequential classifier was designed-one that first identifies non-wingless (WNT) and non-sonic hedgehog (SHH) MB and then differentiates therapeutically relevant WNT from SHH. Further, a classifier that distinguishes high-risk group 3 from group 4 MB was developed. An independent, binary subgroup analysis was conducted to uncover radiomics features unique to infantile versus childhood SHH subgroups. The best-performing models from six candidate classifiers were selected, and performance was measured on holdout test sets. CIs were obtained by bootstrapping the test sets for 2000 random samples. Model accuracy score was compared with the no-information rate using the Wald test. Results The study cohort comprised 263 patients (mean age ± SD at diagnosis, 87 months ± 60; 166 boys). A two-stage classifier outperformed a single-stage multiclass classifier. The combined, sequential classifier achieved a microaveraged F1 score of 88% and a binary F1 score of 95% specifically for WNT. A group 3 versus group 4 classifier achieved an area under the receiver operating characteristic curve of 98%. Of the Image Biomarker Standardization Initiative features, texture and first-order intensity features were most contributory across the molecular subgroups. Conclusion An MRI-based machine learning decision path allowed identification of the four clinically relevant molecular pediatric medulloblastoma subgroups. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chaudhary and Bapuraj in this issue.
Authors
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; 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
MLA Citation
Zhang, Michael, et al. “MRI Radiogenomics of Pediatric Medulloblastoma: A Multicenter Study.Radiology, vol. 304, no. 2, Aug. 2022, pp. 406–16. Pubmed, doi:10.1148/radiol.212137.
URI
https://scholars.duke.edu/individual/pub1517750
PMID
35438562
Source
pubmed
Published In
Radiology
Volume
304
Published Date
Start Page
406
End Page
416
DOI
10.1148/radiol.212137

Successful Neonatal, Intraoperative Neuromonitoring in the Surgical Correction of a Thoracic Dermal Sinus Tract: Technical Note.

INTRODUCTION: Intraoperative neuromonitoring (IONM) is commonly used during surgery of the spine and spinal cord for early surveillance of iatrogenic injury to the central and peripheral nervous system. However, for infants and young children under 3 years of age, the use of IONM is challenging due to incomplete central and peripheral myelination. CASE PRESENTATION: We report a case of a T4-T6 dermal sinus tract (DST) that was resected on day of life 23, with the successful use of IONM. CONCLUSION: To our knowledge, this is the youngest reported case of the use of IONM in the surgical correction of a DST in a neonatal patient. This case demonstrates the potential efficacy of IONM in neonatal spine surgery and the techniques used to adapt the technology to an immature nervous system.
Authors
Shalita, C; Sankey, EW; Bergin, SM; McManigle, J; Buckley, AF; Radtke, R; Torres, C; Dear, GL; Thompson, EM
MLA Citation
Shalita, Chidyaonga, et al. “Successful Neonatal, Intraoperative Neuromonitoring in the Surgical Correction of a Thoracic Dermal Sinus Tract: Technical Note.Pediatr Neurosurg, vol. 57, no. 4, 2022, pp. 295–300. Pubmed, doi:10.1159/000524924.
URI
https://scholars.duke.edu/individual/pub1520632
PMID
35512661
Source
pubmed
Published In
Pediatr Neurosurg
Volume
57
Published Date
Start Page
295
End Page
300
DOI
10.1159/000524924

Research Areas:

Brain Neoplasms
Muser Mentor
Neoplasm Metastasis
Neoplasm Proteins
Neoplasm Recurrence, Local
Neoplasms, Experimental
Neoplasms, Nerve Tissue
Spine--Abnormalities--Surgery