Medical Microbiology and Immunology

Tomoaki Ogino, Ph.D.

Ogino

Associate Professor
Virology
Office: HEB 204
Telephone: 419-383-4591
Fax:  419-383-3002
E-mail: Tomoaki.Ogino@utoledo.edu

 

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Dr. Ogino's research interests include studies on gene expression of RNA viruses in higher eukaryotic cells. His current research focuses on understanding the fundamental molecular mechanisms of RNA synthesis and processing catalyzed by multifunctional RNA-dependent RNA polymerase large (L) proteins of nonsegmented negative strand (NNS) RNA viruses. NNS RNA viruses belonging to the Mononegavirales order include many life-threatening human pathogens, such as rabies (Rhabdoviridae), measles (Paramyxoviridae), Nipah (Paramyxoviridae), respiratory syncytial (Pneumoviridae), and Ebola (Filoviridae). However, there is presently no effective drug against them. Although these viruses manifest different morphological and biological properties, the structures of their genomes and L proteins are similar. Therefore, their basic strategies for genome transcription and replication are expected to be similar as well. Despite the fact that these L proteins are essential for virus replication, their precise functions remain elusive. Dr. Ogino's research goals are to define the enzymatic and regulatory roles of NNS RNA viral L proteins in transcription and replication at the molecular level and to develop specific drugs against them.

 Dr. Ogino's accomplishments include the discovery of a novel mechanism of mRNA capping catalyzed by the L protein of rhabdoviruses, such as vesicular stomatitis virus, Chandipura virus, and rabies virus. A structural hallmark of eukaryotic mRNA is the presence of the 5′-terminal cap structure, which is essential for efficient translation and stability. His studies demonstrated that the mechanism of mRNA capping by rhabdoviral enzymes is fundamentally different from that by eukaryotic enzymes. One of the key viral enzymes, which Dr. Ogino named, GDP polyribonucleotidyltransferase (PRNTase, EC 2.7.7.88), carries out covalent catalysis of the RNA transfer to GDP to generate the cap structure on viral mRNAs. PRNTase is present as an enzymatic domain in the rhabdoviral L proteins and is essential for viral gene expression and propagation in host cells. Importantly, PRNTase domains are strikingly conserved among all known NNS RNA viruses including significant human pathogens, such as measles, Nipah, respiratory syncytial, and Ebola. Furthermore, Dr. Ogino's laboratory recently discovered that rhabdoviral L proteins employ a unique structural element (named "priming-capping loop") in the PRNTase domain to mediate transcription initiation and co-transcriptional mRNA capping during a dynamic stop-start transcription cycle. These findings highlighting the differences between host and viral mRNA capping machineries suggest that the NNS RNA viral PRNTase domain has the potential to serve as an attractive target for developing anti-viral agents.

 Dr. Ogino's research aims to further dissect catalytic and regulatory roles of NNS RNA viral L proteins in RNA biosynthesis. In addition to mRNA 5′-capping, the L proteins catalyze RNA synthesis, mRNA cap methylation at guanine-N7- and ribose-2′-O-positions, and 3′-polyadenylation. However, the mechanisms of these mRNA modifications by a transcribing L protein remain largely unknown. A key goal of his current project is to understand how the enzymatic domains of the NNS RNA viral L proteins coordinately carry out respective steps of RNA synthesis and processing during the transcription cycle. Dr. Ogino hypothesizes that NNS viral L proteins catalyze common enzymatic reactions via evolutionary conserved elements, but manifest virus-specific functions via diversified elements. His research endeavors are to reveal the common and virus-specific functions of the NNS RNA viral L proteins in RNA biosynthesis and to provide foundations for the future development of antiviral agents against them.

 Dr. Ogino received his Ph.D. degree in Pharmaceutical Sciences from Kitasato University in Japan. He completed his post-doctoral training at Cleveland Clinic in the laboratory of Dr. Amiya K. Banerjee. After working as a Staff Scientist at Cleveland Clinic, he was appointed to the faculty of Case Western Reserve University at the level of Assistant Professor. Dr. Ogino joined the Department of Medical Microbiology and Immunology in April of 2020.

Grant Funding:

NIH/NIAID, R01 AI146172, PI: Tomoaki Ogino, Dissecting catalytic and regulatory functions of nonsegmented negative strand RNA viral polymerases, 2019–2024

 NIH/NCI, R01 CA068782, PI: Ganes C Sen, Anti-viral actions of interferon, 2016–2021, Role: Co-Investigator

 STERIS Corporation for Infectious Diseases Research Support for Investigators, PI: Tomoaki Ogino, Screening for small-molecule antiviral agents against non-segmented negative strand RNA viruses, 2015–2016

 NIH/NIAID, R01 AI093569, PI: Tomoaki Ogino, mRNA synthesis and capping in nonsegmented negative strand RNA viruses, 2012–2018

Publications:

NCBI My Bibliography

Gould, J.R., Qiu, S., Shang, Q., Ogino, T., Prevelige, P.E. Jr, Petit, C.M., and Green, T.J. (2020) The connector domain of vesicular stomatitis virus large protein interacts with the viral phosphoprotein. J. Virol. 94: e01729-19

 Ogino, M., Fedorov, Y., Adams, D.J., Okada, K., Ito N., Sugiyama, M., and Ogino, T. (2019) Vesiculopolins, a new class of anti-vesiculoviral compounds, inhibit transcription initiation of vesiculoviruses. Viruses 11:856

 Ogino, T.* and Green, T.J. (2019) RNA synthesis and capping by non-segmented negative strand RNA viral polymerases: Lessons from a prototypic virus. in: Richard, M. and Te Velthuis, A. (Eds.), RNA Virus Polymerases: Forming Bonds and Balancing Errors. Front. Microbiol. 10:1490, Review (* corresponding author)

 Ogino, T.* and Green, T.J. (2019) Transcriptional control and mRNA capping by the GDP polyribonucleotidyltransferase domain of the rabies virus large protein. Viruses 11:E504, Review (* corresponding author)

 Ogino, M., Gupta, N., Green, T.J., and Ogino, T. (2019) A dual-functional priming-capping loop of rhabdoviral RNA polymerases directs terminal de novo initiation and capping intermediate formation. Nucleic Acids Res. 47:299-309

 Ogino, M. and Ogino, T. (2017) 5′-Phospho-RNA acceptor specificity of GDP polyribonucleotidyltransferase of vesicular stomatitis virus in mRNA capping. J. Virol. 91:e02322-16

 Ogino, M., Ito, N., Sugiyama, M., and Ogino, T. (2016) The rabies virus L protein catalyzes mRNA capping with GDP polyribonucleotidyltransferase activity. Viruses 8:144

 Neubauer, J., Ogino, M., Green, T.J., and Ogino, T. (2016) Signature motifs of GDP polyribonucleotidyltransferase, a non-segmented negative strand RNA viral mRNA capping enzyme, domain in the L protein are required for covalent enzyme-pRNA intermediate formation. Nucleic Acids Res. 44:330-341

 Qiu, S., Ogino, M., Luo, M., Ogino, T.*, and Green, T.J.* (2016) Structure and function of the N-terminal domain of the vesicular stomatitis virus RNA polymerase, J. Virol. 90:715-724 (* co-corresponding authors)

 Ogino, T. (2014) Capping of vesicular stomatitis virus pre-mRNA is required for accurate selection of transcription stop-start sites and virus propagation. Nucleic Acids Res. 42:12112-12125

 Ogino, T. (2013) In vitro capping and transcription of rhabdoviruses. Methods 59:188-198. Review.

 Fensterl, V., Wetzel, J.L., Ramachandran, S., Ogino, T., Stohlman, S.A., Bergmann, C.C., Diamond, M.S., Virgin, H.W., and Sen, G.C. (2012) Interferon-induced Ifit2/ISG54 protects mice from lethal VSV neuropathogenesis. PLoS Pathog. 8:e1002712.

 Ogino, T.* and Banerjee, A.K.* (2011) An unconventional pathway of mRNA cap formation by vesiculoviruses. Virus Res. 162:100-109. Review. (* co-corresponding authors)

 Ogino, T., Yadav, S.P., and Banerjee, A.K. (2010) Histidine-mediated RNA transfer to GDP for unique mRNA capping by vesicular stomatitis virus RNA polymerase. Proc. Natl. Acad. Sci. U.S.A. 107:3463-3468.

 Ogino, T. and Banerjee, A.K. (2010) The HR motif in the RNA-dependent RNA polymerase L protein of Chandipura virus is required for unconventional mRNA-capping activity. J Gen. Virol. 91:1311-1314.

 Ogino, T. and Banerjee, A.K. (2008) Formation of guanosine(5′)tetraphospho(5′)adenosine cap structure by an unconventional mRNA capping enzyme of vesicular stomatitis virus. J. Virol. 82:7729-7734.

 Ogino, T. and Banerjee, A.K. (2007) Unconventional mechanism of mRNA capping by the RNA-dependent RNA polymerase of vesicular stomatitis virus. Mol. Cell 25:85-97.


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Last Updated: 4/22/20