Matthias Gromeier

Overview:

Neuro-Oncology
Protein Synthesis Regulation
Signal Transduction
Growth & Proliferation Control in Cancer
Oncolytic Viruses
Viral Neuropathogenesis
Immunization Vectors

Positions:

Professor of Neurosurgery

Neurosurgery, Neuro-Oncology
School of Medicine

Professor in Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Professor in Medicine

Medicine, Infectious Diseases
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1992

University of Hamburg (Germany)

Postdoctoral fellow, Molecular Genetics & Microbiology

State University of New York at Stony Brook

Postdoctoral Associate, Molecular Genetics & Microbiology

State University of New York at Stony Brook

Grants:

Cancer Immunotherapy Through Intratumoral Activation of Recall Responses

Administered By
Neurosurgery
Role
Principal Investigator
Start Date
End Date

Oncolytic Immunotherapy of Glioblastoma with Recombinant Poliovirus

Administered By
Neurosurgery
Role
Principal Investigator
Start Date
End Date

Phase II/III Manufacture of the Oncolytic Poliovirus Chimera, PVSRIPO

Administered By
Neurosurgery
Role
Principal Investigator
Start Date
End Date

Oncolytic poliovirus therapy of malignant glioma

Administered By
Neurosurgery, Neuro-Oncology
Role
Principal Investigator
Start Date
End Date

Transgenic Mouse Model for the Common Cold

Administered By
Neurosurgery, Neuro-Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1.

The mechanistic target of rapamycin (mTOR) integrates numerous stimuli and coordinates the adaptive response of many cellular processes. To accomplish this, mTOR associates with distinct co-factors that determine its signaling output. While many of these co-factors are known, in many cases their function and regulation remain opaque. The MAPK-interacting kinase (MNK) contributes to rapamycin resistance in cancer cells. Here, we demonstrate that MNK sustains mTORC1 activity following rapamycin treatment and contributes to mTORC1 signaling following T cell activation and growth stimuli in cancer cells. We determine that MNK engages with mTORC1, promotes mTORC1 association with the phosphatidyl inositol 3' kinase-related kinase (PIKK) stabilizer, TELO2, and facilitates mTORC1:substrate binding. Moreover, our data suggest that DEPTOR, the endogenous inhibitor of mTOR, opposes mTORC1:substrate association by preventing TELO2:mTORC1 binding. Thus, MNK orchestrates counterbalancing forces that regulate mTORC1 enzymatic activity.
Authors
Brown, MC; Gromeier, M
MLA Citation
Brown, Michael C., and Matthias Gromeier. “MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1..” Cell Rep, vol. 18, no. 6, Feb. 2017, pp. 1444–57. Pubmed, doi:10.1016/j.celrep.2017.01.023.
URI
https://scholars.duke.edu/individual/pub1176066
PMID
28178522
Source
pubmed
Published In
Cell Reports
Volume
18
Published Date
Start Page
1444
End Page
1457
DOI
10.1016/j.celrep.2017.01.023

Adaptation of an ICAM-1-tropic enterovirus to the mouse respiratory tract.

Respiratory tract (RT) infections by members of the enterovirus (EV) genus of the Picornaviridae family are the most frequent cause for the common cold and a major factor in the exacerbation of chronic pulmonary diseases. The lack of a practical small-animal model for these infections has obstructed insight into pathogenic mechanisms of the common cold and their role in chronic RT illness and has hampered preclinical evaluation of antiviral strategies. Despite significant efforts, it has been difficult to devise rodent models that exhibit viral replication in the RT. This is due mainly to well-known intracellular host restrictions of EVs with RT tropism in rodent cells. We report the evolution of variants of the common-cold-causing coxsackievirus A21, an EV with tropism for the human intercellular adhesion molecule 1 (hICAM-1), through serial passage in the lungs of mice transgenic for the hICAM-1 gene. This process was accompanied by multiple changes in the viral genome, suggesting exquisite adaptation of hICAM-1-tropic enteroviruses to the specific growth conditions within the RT. In vivo mouse RT-adapted, variant coxsackievirus A21 exhibited replication competence in the lungs of hICAM-1 transgenic mice, providing a basis for unraveling EV-host interactions in the mouse RT.
Authors
Wang, ES; Dobrikova, E; Goetz, C; Dufresne, AT; Gromeier, M
MLA Citation
Wang, Eric S., et al. “Adaptation of an ICAM-1-tropic enterovirus to the mouse respiratory tract..” J Virol, vol. 85, no. 11, June 2011, pp. 5606–17. Pubmed, doi:10.1128/JVI.01502-10.
URI
https://scholars.duke.edu/individual/pub732031
PMID
21450825
Source
pubmed
Published In
J Virol
Volume
85
Published Date
Start Page
5606
End Page
5617
DOI
10.1128/JVI.01502-10

Viruses in the treatment of malignant glioma.

Authors
Everson, RG; Gromeier, M; Sampson, JH
MLA Citation
Everson, Richard G., et al. “Viruses in the treatment of malignant glioma..” Expert Rev Neurother, vol. 7, no. 4, Apr. 2007, pp. 321–24. Pubmed, doi:10.1586/14737175.7.4.321.
URI
https://scholars.duke.edu/individual/pub721597
PMID
17425484
Source
pubmed
Published In
Expert Rev Neurother
Volume
7
Published Date
Start Page
321
End Page
324
DOI
10.1586/14737175.7.4.321

Poliovirus receptor CD155-targeted oncolysis of glioma.

Cell adhesion molecules of the immunoglobulin superfamily are aberrantly expressed in malignant glioma. Amongst these, the human poliovirus receptor CD155 provides a molecular target for therapeutic intervention with oncolytic poliovirus recombinants. Poliovirus has been genetically modified through insertion of regulatory sequences derived from human rhinovirus type 2 to selectively replicate within and destroy cancerous cells. Efficacious oncolysis mediated by poliovirus derivatives depends on the presence of CD155 in targeted tumors. To prepare oncolytic polioviruses for clinical application, we have developed a series of assays in high-grade malignant glioma (HGL) to characterize CD155 expression levels and susceptibility to oncolytic poliovirus recombinants. Analysis of 6 HGL cases indicates that CD155 is expressed in these tumors and in primary cell lines derived from these tumors. Upregulation of the molecular target CD155 rendered explant cultures of all studied tumors highly susceptible to a prototype oncolytic poliovirus recombinant. Our observations support the clinical application of such agents against HGL.
Authors
Merrill, MK; Bernhardt, G; Sampson, JH; Wikstrand, CJ; Bigner, DD; Gromeier, M
MLA Citation
Merrill, Melinda K., et al. “Poliovirus receptor CD155-targeted oncolysis of glioma..” Neuro Oncol, vol. 6, no. 3, July 2004, pp. 208–17. Pubmed, doi:10.1215/S1152851703000577.
URI
https://scholars.duke.edu/individual/pub721614
PMID
15279713
Source
pubmed
Published In
Neuro Oncology
Volume
6
Published Date
Start Page
208
End Page
217
DOI
10.1215/S1152851703000577

A small yeast RNA blocks hepatitis C virus internal ribosome entry site (HCV IRES)-mediated translation and inhibits replication of a chimeric poliovirus under translational control of the HCV IRES element.

Hepatitis C virus (HCV) infection frequently leads to chronic hepatitis and cirrhosis of the liver and has been linked to development of hepatocellular carcinoma. We previously identified a small yeast RNA (IRNA) capable of specifically inhibiting poliovirus (PV) internal ribosome entry site (IRES)-mediated translation. Here we report that IRNA specifically inhibits HCV IRES-mediated translation both in vivo and in vitro. A number of human hepatoma (Huh-7) cell lines expressing IRNA were prepared and characterized. Constitutive expression of IRNA was not detrimental to cell growth. HCV IRES-mediated cap-independent translation was markedly inhibited in cells constitutively expressing IRNA compared to control hepatoma cells. However, cap-dependent translation was not significantly affected in these cell lines. Additionally, Huh-7 cells constitutively expressing IRNA became refractory to infection by a PV-HCV chimera in which the PV IRES is replaced by the HCV IRES. In contrast, replication of a PV-encephalomyocarditis virus (EMCV) chimera containing the EMCV IRES element was not affected significantly in the IRNA-producing cell line. Finally, the binding of the La autoantigen to the HCV IRES element was specifically and efficiently competed by IRNA. These results provide a basis for development of novel drugs effective against HCV infection.
Authors
Das, S; Ott, M; Yamane, A; Tsai, W; Gromeier, M; Lahser, F; Gupta, S; Dasgupta, A
URI
https://scholars.duke.edu/individual/pub721584
PMID
9621022
Source
pubmed
Published In
Journal of Virology
Volume
72
Published Date
Start Page
5638
End Page
5647