GRDZELISHVILI LAB: Molecular Virology and Oncolytic Virotherapy

Left to Right: Valery Grdzelishvili, Cassandra (Cassie) Catacalos, Jacob Hawkins, Aroosh Goje, Nathaniel Foret, Irakli Mataradze, Charlotte Johnstone

Valery Z. Grdzelishvili, Ph.D.

Professor, Molecular Virology and Cancer Therapy

Dr. Grdzelishvili’s publications at PubMed
Dr. Grdzelishvili’s Google Scholar Profile
Grdzelishvili Lab Twitter: https://twitter.com/Virology_Lab

RESEARCH INTERESTS: molecular virology, cancer biology, anticancer therapy based on replication-competent viruses (“oncolytic virotherapy”), virus-host interactions in normal and cancer cells, host factors of virus replication in normal and cancer cells, innate immunity in normal and cancer cells, virus-based gene therapy, vaccine vectors

Valery Z. Grdzelishvili, Ph.D.

Research Interests

Dr. Grdzelishvili’s laboratory is focused on molecular biology and applications of nonsegmented negative-strand (NNS) RNA viruses (order Mononegavirales). The major focus is the exploitation of existing and engineering new NNS RNA viruses [vesicular stomatitis virus (VSV) in particular] as clinically important anticancer (“oncolytic”) agents. We are particularly interested in the identification and characterization of cellular and viral determinants of susceptibility or resistance of pancreatic cancer cells to VSV and other oncolytic viruses. Other projects are focused on mechanistic understanding of viral replication cycle of NNS RNA viruses, which is fundamental to developing reagents to prevent and combat viral diseases. The order Mononegavirales includes many important human and animal pathogens, such as rabies, measles, Ebola, Marburg, Nipah, Hendra, and other viruses.

Academic Degrees

Professional Experience

Selected Peer-Reviewed Publications (see all publications in the “Lab Publications” tab)

  1. Goad DW, Nesmelova AY, Yohe LR, Grdzelishvili VZ. 2023 “Intertumoral heterogeneity impacts oncolytic vesicular stomatitis virus efficacy in mouse pancreatic cancer cells” Journal of Virology 2023 Sep 6:e0100523. doi: 10.1128/jvi.01005-23. Epub ahead of print. [PMID: 37671865]
  2. Goad D.W., Bressy C., Holbrook M.C., and Grdzelishvili VZ. 2022 “Acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus” Molecular Therapy Oncolytics. 2022 24:59-76. [PMID: 34977342]
  3. Seegers S.L., Frasier C., Greene S., Nesmelova I.V., and Grdzelishvili VZ. 2019 “Experimental Evolution Generates Novel Oncolytic Vesicular Stomatitis Viruses With Improved Replication in Virus-Resistant Pancreatic Cancer Cells”. Journal of Virology, 2020 Jan 17;94(3):e01643-19. [PMID: 31694943]
  4. Bressy C, Droby GN, Maldonado BD, Steuerwald N, and Grdzelishvili VZ. 2019 “Cell Cycle Arrest in G(2)/M Phase Enhances Replication of Interferon-Sensitive Cytoplasmic RNA Viruses via Inhibition of Antiviral Gene Expression”. Journal of Virology, 2019 Feb 5;93(4). pii: e01885-18. [PMID: 30487274]
  5. Felt S.A., Droby G.N., Grdzelishvili V.Z. 2017 “Ruxolitinib and polycation combination treatment overcomes multiple mechanisms of resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus” Journal of Virology, 2017, 91(16)
  6. Hastie E., Cataldi M., Moerdyk-Schauwecker M.J., Felt S.A., Steuerwald N., Grdzelishvili V.Z. 2016 “Novel biomarkers of resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus” Oncotarget. 2016 [PMID: 27533247]
  7. Cataldi M., Shah N.R., Felt S.A., Grdzelishvili V.Z. 2015 “Breaking resistance of pancreatic cancer cells to an attenuated vesicular stomatitis virus through a novel activity of IKK inhibitor TPCA-1”. Virology. 2015 485:340-354. [PMID: 26331681]
  8. Hastie E., Cataldi M., Steuerwald N., and *Grdzelishvili V.Z. 2015 “An unexpected inhibition of antiviral signaling by virus-encoded tumor suppressor p53 in pancreatic cancer cells” Virology. 483:126-140. [PMID: 25965802]
  9. Felt S.A., Moerdyk-Schauwecker M., and Grdzelishvili V.Z.  2015 “Induction of apoptosis in pancreatic cancer cells by vesicular stomatitis virus“, Virology, 474:163-173 [PMID:25463614]
  10. Moerdyk-Schauwecker M., Shah N.R. Murphy A.M., Hastie, E., Mukherjee, P., and Grdzelishvili V.Z.  2013 “Resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus: role of type I interferon signaling”, Virology, 436:221-34 [PMID:23246628]
  11. Murphy A. M., Besmer D. M., Moerdyk-Schauwecker M., Moestl N., Ornelles D., Mukherjee P., and Grdzelishvili V. Z.  2012 “Vesicular stomatitis virus as an oncolytic agent against pancreatic ductal adenocarcinoma” Journal of Virology, 86:3073-87. [PMID: 22238308]
 

ONCOLYTIC VIROTHERAPY OVERVIEW

(the illustration was created by Dr. Eric Hastie and is from Hastie and Grdzelishvili 2012 “Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer” Journal of General Virology, 93:2529-45) 

Microsoft Word - 17333195-file00.docx

Scheme of VSV-based OV therapy. (a) Reverse genetics allows the generation of a recombinant VSV encoding a foreign gene of interest between the VSV G and L genes. The asterisk above M indicates M protein mutation(s) resulting in VSV attenuation in normal cells. Plasmids encoding VSV replication machinery and the modified genome are co-transfected into a cell line, and complete virions are produced and amplified using good manufacturing practices. (b) For evaluation of oncolytic efficacy, VSV can be administered directly, via cell-based delivery, or in combination with other treatments (chemotherapy, radiotherapy, or other OVs). (c) In infected cells, VSV recombinants may express a foreign gene that facilitates the killing of the adjacent uninfected cancer cells (e.g. suicide-gene approach or immunostimulation). Innate antiviral responses and other mechanisms prevent cell death in normal cells. Ideally, stimulation of innate and adaptive immune cells by VSV and/or the foreign gene product should lead to tumor-specific immune responses, including memory responses that prevent cancer recurrence.

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