Michael Brown
Assistant Professor in Neurosurgery
Dr. Brown’s research focuses on leveraging intratumor innate immunity for cancer immunotherapy, particularly in the context of malignant brain tumors. Dr. Brown's lab uses mouse cancer models, ex vivo human tumor slice culture assays, and clinical trial associated specimens to decode mechanisms by which intratumor innate immune cells control cancer immune surveillance and develop novel in situ vaccine approaches that engage endogenous antitumor T cells. The Brown lab also collaborates with clinicians and other research groups to facilitate the translation of novel therapies, define determinants of successful immunotherapy, and elucidate mechanisms explaining immune dysfunction in patients with cancer.
Current Appointments & Affiliations
- Assistant Professor in Neurosurgery, Neurosurgery, Neuro-Oncology, Neurosurgery 2022
- Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 2023
Contact Information
- Background
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Education, Training, & Certifications
- Ph.D., Duke University 2016
- Research
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Selected Grants
- ATRXmutations,innate immune activation and therapeutic vunerabilityin malignant gliomas awarded by National Institutes of Health 2022 - 2027
- Reviving cancer immune surveillance with CD4 T cell help awarded by National Institutes of Health 2022 - 2025
- Reviving cancer immune surveillance with CD4 T cell help awarded by National Institutes of Health 2021 - 2023
- Innate Antiviral Signals for Cancer Immunotherapy awarded by National Institutes of Health 2018 - 2023
- Is Low Tumor Mutational Burden Predictive of Response to Oncolytic Polio Virus Therapy in Recurrent Glioblastoma? awarded by National Institutes of Health 2019 - 2022
- Cancer Immunotherapy Through Intratumoral Activation of Recall Responses awarded by National Institutes of Health 2018 - 2021
- Cancer Immunotherapy Through Intratumoral Activation of Recall Responses awarded by National Cancer Center 2017 - 2019
- Oncolytic Virotherapy of Meningeal Cancer awarded by National Institutes of Health 2009 - 2015
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External Relationships
- Istari Oncology
- Menarini Ricerche S.p.A.
- Publications & Artistic Works
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Selected Publications
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Academic Articles
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Brown, Michael C., Georgia M. Beasley, Zachary P. McKay, Yuanfan Yang, Annick Desjardins, Dina M. Randazzo, Daniel Landi, et al. “Intratumor childhood vaccine-specific CD4+ T-cell recall coordinates antitumor CD8+ T cells and eosinophils.” J Immunother Cancer 11, no. 4 (April 2023). https://doi.org/10.1136/jitc-2022-006463.Full Text Link to Item
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Li, Sean, Roger McLendon, Eric Sankey, Reb Kornahrens, Anne-Marie Lyne, Florence Marie Géraldine Cavalli, Zachary McKay, et al. “CD155 is a putative therapeutic target in medulloblastoma.” Clin Transl Oncol 25, no. 3 (March 2023): 696–705. https://doi.org/10.1007/s12094-022-02975-9.Full Text Link to Item
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Beasley, Georgia M., Michael C. Brown, Norma E. Farrow, Karenia Landa, Rami N. Al-Rohil, Maria Angelica Selim, Aaron D. Therien, et al. “Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma.” J Immunother Cancer 10, no. 9 (September 2022). https://doi.org/10.1136/jitc-2022-005052.Full Text Link to Item
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Dobrikov, Mikhail I., Elena Y. Dobrikova, Zachary P. McKay, Jonathan P. Kastan, Michael C. Brown, and Matthias Gromeier. “PKR Binds Enterovirus IRESs, Displaces Host Translation Factors, and Impairs Viral Translation to Enable Innate Antiviral Signaling.” Mbio 13, no. 3 (June 28, 2022): e0085422. https://doi.org/10.1128/mbio.00854-22.Full Text Link to Item
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Sarver, Melissa, Michael C. Brown, Kristen E. Rhodin, April K. S. Salama, and Georgia M. Beasley. “Predictive factors of neoadjuvant immune checkpoint blockade in melanoma.” Hum Vaccin Immunother 18, no. 3 (May 31, 2022): 1943987. https://doi.org/10.1080/21645515.2021.1943987.Full Text Link to Item
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Low, Justin T., Vidyalakshmi Chandramohan, Michelle L. Bowie, Michael C. Brown, Matthew S. Waitkus, Aaron Briley, Kevin Stevenson, et al. “Epigenetic STING silencing is developmentally conserved in gliomas and can be rescued by methyltransferase inhibition.” Cancer Cell 40, no. 5 (May 9, 2022): 439–40. https://doi.org/10.1016/j.ccell.2022.04.009.Full Text Link to Item
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Brown, Michael C., David M. Ashley, and Mustafa Khasraw. “Low tumor mutational burden and immunotherapy in gliomas.” Trends Cancer 8, no. 5 (May 2022): 345–46. https://doi.org/10.1016/j.trecan.2022.01.006.Full Text Link to Item
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Brown, Michael. “Engaging Pattern Recognition Receptors in Solid Tumors to Generate Systemic Antitumor Immunity.” Cancer Treat Res 183 (2022): 91–129. https://doi.org/10.1007/978-3-030-96376-7_3.Full Text Link to Item
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Kastan, Jonathan P., Martine W. Tremblay, Michael C. Brown, Joseph D. Trimarco, Elena Y. Dobrikova, Mikhail I. Dobrikov, and Matthias Gromeier. “Enterovirus 2Apro Cleavage of the YTHDF m6A Readers Implicates YTHDF3 as a Mediator of Type I Interferon-Driven JAK/STAT Signaling.” Mbio 12, no. 2 (April 13, 2021). https://doi.org/10.1128/mBio.00116-21.Full Text Link to Item
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Brown, Michael C., Mubeen M. Mosaheb, Malte Mohme, Zachary P. McKay, Eda K. Holl, Jonathan P. Kastan, Yuanfan Yang, et al. “Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling.” Nat Commun 12, no. 1 (March 25, 2021): 1858. https://doi.org/10.1038/s41467-021-22088-1.Full Text Link to Item
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McKay, Zachary P., Michael C. Brown, and Matthias Gromeier. “Aryl Hydrocarbon Receptor Signaling Controls CD155 Expression on Macrophages and Mediates Tumor Immunosuppression.” J Immunol 206, no. 6 (March 15, 2021): 1385–94. https://doi.org/10.4049/jimmunol.2000792.Full Text Link to Item
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Gromeier, Matthias, Michael C. Brown, Gao Zhang, Xiang Lin, Yeqing Chen, Zhi Wei, Nike Beaubier, et al. “Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.” Nat Commun 12, no. 1 (January 13, 2021): 352. https://doi.org/10.1038/s41467-020-20469-6.Full Text Open Access Copy Link to Item
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Mosaheb, Mubeen M., Michael C. Brown, Elena Y. Dobrikova, Mikhail I. Dobrikov, and Matthias Gromeier. “Harnessing virus tropism for dendritic cells for vaccine design.” Curr Opin Virol 44 (October 2020): 73–80. https://doi.org/10.1016/j.coviro.2020.07.012.Full Text Link to Item
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Mosaheb, Mubeen M., Elena Y. Dobrikova, Michael C. Brown, Yuanfan Yang, Jana Cable, Hideho Okada, Smita K. Nair, Darell D. Bigner, David M. Ashley, and Matthias Gromeier. “Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity.” Nat Commun 11, no. 1 (January 27, 2020): 524. https://doi.org/10.1038/s41467-019-13939-z.Full Text Link to Item
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Puza, Charles J., Elizabeth Schell Bressler, Alicia M. Terando, John Harrison Howard, Michael C. Brown, Brent Hanks, April K. S. Salama, and Georgia M. Beasley. “The Emerging Role of Surgery for Patients With Advanced Melanoma Treated With Immunotherapy.” J Surg Res 236 (April 2019): 209–15. https://doi.org/10.1016/j.jss.2018.11.045.Full Text Link to Item
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Walton, Ross W., Michael C. Brown, Matthew T. Sacco, and Matthias Gromeier. “Engineered Oncolytic Poliovirus PVSRIPO Subverts MDA5-Dependent Innate Immune Responses in Cancer Cells.” J Virol 92, no. 19 (October 1, 2018). https://doi.org/10.1128/JVI.00879-18.Full Text Link to Item
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Thompson, Eric M., Michael Brown, Elena Dobrikova, Vijay Ramaswamy, Michael D. Taylor, Roger McLendon, Jennifer Sanks, Vidya Chandramohan, Darell Bigner, and Matthias Gromeier. “Poliovirus Receptor (CD155) Expression in Pediatric Brain Tumors Mediates Oncolysis of Medulloblastoma and Pleomorphic Xanthoastrocytoma.” J Neuropathol Exp Neurol 77, no. 8 (August 1, 2018): 696–702. https://doi.org/10.1093/jnen/nly045.Full Text Link to Item
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Bryant, Jeffrey D., Michael C. Brown, Mikhail I. Dobrikov, Elena Y. Dobrikova, Sarah L. Gemberling, Qing Zhang, and Matthias Gromeier. “Regulation of Hypoxia-Inducible Factor 1α during Hypoxia by DAP5-Induced Translation of PHD2.” Mol Cell Biol 38, no. 11 (June 1, 2018). https://doi.org/10.1128/MCB.00647-17.Full Text Link to Item
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Evans, Myron K., Michael C. Brown, Joseph Geradts, Xuhui Bao, Timothy J. Robinson, Mohit Kumar Jolly, Peter B. Vermeulen, et al. “XIAP Regulation by MNK Links MAPK and NFκB Signaling to Determine an Aggressive Breast Cancer Phenotype.” Cancer Res 78, no. 7 (April 1, 2018): 1726–38. https://doi.org/10.1158/0008-5472.CAN-17-1667.Full Text Link to Item
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Brown, Michael C., Eda K. Holl, David Boczkowski, Elena Dobrikova, Mubeen Mosaheb, Vidya Chandramohan, Darell D. Bigner, Matthias Gromeier, and Smita K. Nair. “Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs.” Sci Transl Med 9, no. 408 (September 20, 2017). https://doi.org/10.1126/scitranslmed.aan4220.Full Text Link to Item
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Brown, Michael C., and Matthias Gromeier. “MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1.” Cell Rep 18, no. 6 (February 7, 2017): 1444–57. https://doi.org/10.1016/j.celrep.2017.01.023.Full Text Link to Item
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Brown, Michael C., and Matthias Gromeier. “MNK inversely regulates TELO2 vs. DEPTOR to control mTORC1 signaling.” Mol Cell Oncol 4, no. 3 (2017): e1306010. https://doi.org/10.1080/23723556.2017.1306010.Full Text Link to Item
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Holl, Eda K., Michael C. Brown, David Boczkowski, Megan A. McNamara, Daniel J. George, Darell D. Bigner, Matthias Gromeier, and Smita K. Nair. “Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models.” Oncotarget 7, no. 48 (November 29, 2016): 79828–41. https://doi.org/10.18632/oncotarget.12975.Full Text Link to Item
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Brown, Michael C., Eda K. Holl, David Boczkowski, Darell D. Bigner, Matthias Gromeier, and Smita K. Nair. “Abstract A157: Oncolytic poliovirus mediated immune events.” Cancer Immunology Research 4, no. 1_Supplement (January 1, 2016): A157–A157. https://doi.org/10.1158/2326-6074.cricimteatiaacr15-a157.Full Text
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Brown, Michael C., and Matthias Gromeier. “Cytotoxic and immunogenic mechanisms of recombinant oncolytic poliovirus.” Curr Opin Virol 13 (August 2015): 81–85. https://doi.org/10.1016/j.coviro.2015.05.007.Full Text Link to Item
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Brown, Michael C., and Matthias Gromeier. “Oncolytic immunotherapy through tumor-specific translation and cytotoxicity of poliovirus.” Discov Med 19, no. 106 (May 2015): 359–65.Link to Item
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Reynolds, John, Gloria A. Preston, Barrak M. Pressler, Peter Hewins, Michael Brown, Aleeza Roth, Elizabeth Alderman, et al. “Autoimmunity to the alpha 3 chain of type IV collagen in glomerulonephritis is triggered by 'autoantigen complementarity'.” J Autoimmun 59 (May 2015): 8–18. https://doi.org/10.1016/j.jaut.2015.01.003.Full Text Link to Item
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Brown, Michael C., Elena Y. Dobrikova, Mikhail I. Dobrikov, Ross W. Walton, Sarah L. Gemberling, Smita K. Nair, Annick Desjardins, et al. “Oncolytic polio virotherapy of cancer.” Cancer 120, no. 21 (November 1, 2014): 3277–86. https://doi.org/10.1002/cncr.28862.Full Text Link to Item
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Brown, Michael C., Jeffrey D. Bryant, Elena Y. Dobrikova, Mayya Shveygert, Shelton S. Bradrick, Vidyalakshmi Chandramohan, Darell D. Bigner, and Matthias Gromeier. “Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediated effects on the serine/arginine-rich protein kinase.” J Virol 88, no. 22 (November 2014): 13135–48. https://doi.org/10.1128/JVI.01883-14.Full Text Link to Item
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Brown, Michael C., Mikhail I. Dobrikov, and Matthias Gromeier. “Mitogen-activated protein kinase-interacting kinase regulates mTOR/AKT signaling and controls the serine/arginine-rich protein kinase-responsive type 1 internal ribosome entry site-mediated translation and viral oncolysis.” J Virol 88, no. 22 (November 2014): 13149–60. https://doi.org/10.1128/JVI.01884-14.Full Text Link to Item
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Inoue, Makoto, Tomohiro Arikawa, Yu-Hsun Chen, Yasuhiro Moriwaki, Michael Price, Michael Brown, John R. Perfect, and Mari L. Shinohara. “T cells down-regulate macrophage TNF production by IRAK1-mediated IL-10 expression and control innate hyperinflammation.” Proc Natl Acad Sci U S A 111, no. 14 (April 8, 2014): 5295–5300. https://doi.org/10.1073/pnas.1321427111.Full Text Link to Item
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Dobrikov, Mikhail I., Mayya Shveygert, Michael C. Brown, and Matthias Gromeier. “Mitotic phosphorylation of eukaryotic initiation factor 4G1 (eIF4G1) at Ser1232 by Cdk1:cyclin B inhibits eIF4A helicase complex binding with RNA.” Mol Cell Biol 34, no. 3 (February 2014): 439–51. https://doi.org/10.1128/MCB.01046-13.Full Text Link to Item
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Roth, Aleeza J., Michael C. Brown, Rex Neal Smith, Anshul K. Badhwar, Oscar Parente, Hyun chul Chung, Donna O’Dell Bunch, et al. “Anti-LAMP-2 antibodies are not prevalent in patients with antineutrophil cytoplasmic autoantibody glomerulonephritis.” J Am Soc Nephrol 23, no. 3 (March 2012): 545–55. https://doi.org/10.1681/ASN.2011030273.Full Text Link to Item
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Conference Papers
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Brown, Michael, Zachary McKay, Yuanfan Yang, Darell Bigner, Smita Nair, and Matthias Gromeier. “739 Intratumor childhood vaccine-specific CD4+ T cell recall helps antitumor CD8 T cells.” In Journal for Immunotherapy of Cancer, 9:A770–A770. BMJ, 2021. https://doi.org/10.1136/jitc-2021-sitc2021.739.Full Text
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Brown, Michael, Gao Zhang, Kevin Stevenson, Xiang Lin, Yeqing Chen, Zhi Wei, Nike Beaubier, et al. “TUMOR-INTRINSIC AND PERIPHERAL FEATURES ASSOCIATE WITH SURVIVAL AFTER POLIO VIROTHERAPY IN RECURRENT GBM.” In Neuro Oncology, 23:14–14, 2021.Link to Item
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Kelly, Andrea True, Prakash Ambady, Michael Brown, Nicholas Butowski, Robert Cavaliere, William Curry, Annick Desjardins, et al. “LUMINOS-101: Phase 2 study of PVSRIPO with pembrolizumab in recurrent glioblastoma.” In Cancer Research, Vol. 81, 2021.Link to Item
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Low, Justin, Vidyalakshmi Chandramohan, Michelle Bowie, Michael Brown, Matthew Waitkus, Aaron Briley, Kevin Stevenson, et al. “STING IS SILENCED IN GBM BY PROMOTER METHYLATION THAT IS ESTABLISHED BY TISSUE OF ORIGIN.” In Neuro Oncology, 23:4–4, 2021.Link to Item
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Yang, Yuanfan, Michael Brown, Kevin Stevenson, Giselle Lopez, Reb Kornahrens, Gao Zhang, and Matthias Gromeier. “POLIO VIROTHERAPY OF MURINE BRAIN TUMORS INDUCES MICROGLIA PROLIFERATION AND INFLAMMATION THAT IS POTENTIATED BY IMMUNE CHECKPOINT BLOCKADE.” In Neuro Oncology, 23:181–181, 2021.Link to Item
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Frazier, Victoria N., Eda Holl, Michael Brown, David Boczkowski, Karenia Landa, Shelley Hwang, Matthias Gromeier, and Smita K. Nair. “Oncolytic poliovirus immunotherapy for breast cancer.” In Journal of Immunology, Vol. 204, 2020.Link to Item
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Hariharan, Seethalakshmi, Michelle Bowie, Janell Hostettler, Kristen Roso, Yiping He, Martin A. Roskoski, Casey Charbonneau, et al. “INTERPLAY BETWEEN IDH1 AND ATRX MUTATIONS GOVERN INNATE IMMUNE RESPONSES IN GLIOMAS.” In Neuro Oncology, 22:108–108, 2020.Link to Item
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Low, Justin, Michelle Bowie, Vidya Chandramohan, Rebecca Fuller, Andrea Muscat, Michael Brown, Seethalakshmi Hariharan, et al. “STING PROMOTER EPIGENETIC SILENCING IN GLIOBLASTOMA.” In Neuro Oncology, 22:73–73, 2020.Link to Item
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Mosaheb, Mubeen, Daniel Landi, Elena Dobrikova, Michael Brown, Yuanfan Yang, Jana Cable, Hideho Okada, et al. “GENETICALLY STABLE POLIOVIRUS VECTOR CARRYING H3.3K27M ANTIGEN FOR TREATMENT OF DIFFUSE MIDLINE GLIOMA BY INTRAMUSCULAR INJECTION.” In Neuro Oncology, 22:472–472, 2020.Link to Item
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Yang, Yuanfan, Michael Brown, Matthias Gromeier, and Darell Bigner. “ONCOLYTIC POLIOVIRUS AS A PROBE FOR MECHANISMS OF IMMUNE RESISTANCE IN GLIOBLASTOMA.” In Neuro Oncology, 22:231–231, 2020.Link to Item
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Bowie, Michelle, Seethalakshmi Hariharan, Janell Hostettler, Kristen Roso, Yiping He, Christopher Pirozzi, Martin Roskoski, et al. “ATRX MUTATIONS PREDICT RESPONSE TO INNATE BASED THERAPY IN GLIOMA.” In Neuro Oncology, 21:126–126. OXFORD UNIV PRESS INC, 2019.Link to Item
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Gromeier, Matthias, Michael Brown, Nike Beuabier, Hai Yan, Yiping He, Gao Zhang, Annick Desjardins, et al. “TUMOR MUTATIONAL BURDEN PREDICTS RESPONSE TO ONCOLYTIC POLIO/RHINOVIRUS RECOMBINANT (PVSRIPO) IN MALIGNANT GLIOMA PATIENTS: ASSESSMENT OF TRANSCRIPTIONAL AND IMMUNOLOGICAL CORRELATES.” In Neuro Oncology, 21:7–7. OXFORD UNIV PRESS INC, 2019.Link to Item
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Gromeier, Matthias, Mubeen Mosaheb, Elena Dobrikova, Michael Brown, Darell Bigner, and David Ashley. “GENETICALLY STABLE POLIOVIRUS VECTOR PLATFORM FOR DIPG IMMUNOTHERAPY.” In Neuro Oncology, 21:93–93. OXFORD UNIV PRESS INC, 2019.Link to Item
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Bowie, Michelle, David Ashley, Janell Hostettler, Michael Brown, Jeffrey Bryant, Darell Bigner, Matthias Gromeier, and Smita Nair. “DYSFUNCTIONAL STING PATHWAY SIGNALING COMPROMISES INNATE IMMUNITY IN GLIOBLASTOMA.” In Neuro Oncology, 20:127–28. OXFORD UNIV PRESS INC, 2018.Link to Item
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Thompson, Eric, Michael Brown, Elena Dobrikova, Vijay Ramaswamy, Michael Taylor, Roger McLendon, Vidya Chandramohan, Darell Bigner, and Matthias Gromeier. “POLIOVIRUS RECEPTOR (CD155) EXPRESSION IN PEDIATRIC BRAIN TUMORS MEDIATES ONCOLYSIS OF MEDULLOBLASTOMA AND PLEOMORPHIC XANTHOASTROCYTOMA.” In Neuro Oncology, 20:213–213. OXFORD UNIV PRESS INC, 2018.Link to Item
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Landa, Karenia, Eda Holl, Michael Brown, James Herndon, Lars Grimm, Jeremy Force, Darell Bigner, Shelley Hwang, Matthias Gromeier, and Smita Nair. “Abstract LB-302: Oncolytic poliovirus-mediated inflammation and immunity in breast cancer.” In Cancer Research, Vol. 78. American Association for Cancer Research (AACR), 2018. https://doi.org/10.1158/1538-7445.am2018-lb-302.Full Text
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Force, Jeremy, Eda Holl, Michael Brown, Paul Kelly Marcom, Lars Grimm, David Boczkowski, Victoria Frazier, et al. “Recombinant oncolytic poliovirus combined with checkpoint blockade for breast cancer therapy.” In Journal of Clinical Oncology, 36:e12641–e12641. American Society of Clinical Oncology (ASCO), 2018. https://doi.org/10.1200/jco.2018.36.15_suppl.e12641.Full Text
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Bryant, Jeffrey, Michael Brown, and Matthias Gromeier. “Chemotherapy enhances oncolytic recombinant poliovirus efficacy.” In Journal for Immunotherapy of Cancer, Vol. 5. BMC, 2017.Link to Item
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Walton, Ross, Michael Brown, Eda Holl, David Boczkowski, Vidya Chandramohan, Smita Nair, and Matthias Gromeier. “PVSRIPO is an interferon-resistant, immunotherapeutic oncolytic virus.” In Journal for Immunotherapy of Cancer, Vol. 5. BMC, 2017.Link to Item
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Preprints
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Brown, Michael, Zachary McKay, Yuanfan Yang, Georgia Beasley, David Ashley, Darell Bigner, Smita Nair, and Matthias Gromeier. “Intratumor Childhood Vaccine-Specific CD4+T cell Recall Coordinates Antitumor CD8+T cells and Eosinophils.” BioRxiv, 2022. https://doi.org/10.1101/2022.03.14.484260.Full Text
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Yang, Yuanfan, Michael Brown, Gao Zhang, Kevin Stevenson, Malte Mohme, Reb Kornahrens, Darell Bigner, David Ashley, Giselle López, and Matthias Gromeier. “Polio Virotherapy of Malignant Glioma Engages the Tumor Myeloid Infiltrate and Induces Diffuse Microglia Activation.” BioRxiv, 2022. https://doi.org/10.1101/2022.04.19.488771.Full Text
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