Phone (Lab): 704.687.8521
Office: Woodward 486B
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Dr. Grdzelishvili’s laboratory is focused on molecular biology and applications of nonsegmented negative-strand (NNS) RNA viruses (the order Mononegavirales). Currently, the major focus of our laboratory 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 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.
CLICK ON PICTURE
Grdzelishvili’s Lab November 2016 (left to right):
Valery Grdzelishvili, Gaith Droby, Christian Bressy, Arundhati Mohanta, Sara Seegers, Bryant Maldonado,
Travis Porter, Sebastien Felt
ONCOLYTIC VIROTHERAPY OVERVIEW
(from Hastie and Grdzelishvili 2012 “Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer” Journal of General Virology, 93:2529-45)
Scheme of VSV-based OV therapy. (a) Reverse genetics allows 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 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 tumour-specific immune responses, including memory responses that prevent cancer recurrence.